（2025.V2）NCCN临床实践指南：膀胱癌

指南肿瘤内科· 泌尿生殖肿瘤 · 2025

NCCN Guidelines Version 2.2025 Bladder Cancer

*Thomas W. Flaig, MD t/Chair University of Colorado Cancer Center

*Philipp E. Spiess, MD, MS T T W/ice Chair Moffitt Cancer Center

Michael Abern, MD 1D Duke Cancer Institute

Neeraj Agarwal, MD †t Huntsman Cancer Institute at the University of Utah

*Rick Bangs, MBA ¥Patient Advocate

Jovan Begovic, MD $\phi$ UT Southwestern Simmons Comprehensive Cancer Center

Jason Brown, MD, PhD t Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

Mark K. Buyyounouski, MD, MS §Stanford Cancer Institute

Kevin Chan, MD $\varphi$ City of Hope National Medical Center

*Sam S.Chang,MD,MBA1,四Vanderbilt-Ingram Cancer Center

Paul Chang, MD §The Chicago Medicine Comprehensive Cancer Center

Arnold Chin, MD $\omega$ UCLA Jonsson Comprehensive Cancer Center

*Terference Friedlander,MD t UCSF Helen Diller Family

Khurshid A. Guru, MD 1, 可Roswell Park Comprehensive Cancer Center

Harry W. Herr, MD $\varrho$ , Memorial Sloan Kettering Cancer Center

Jean Hoffman-Censits, MD †$\_$Johns Hopkins Kimmel Cancer Center

Hristos Kaimakiotis, MD 同盘University Melvin and Bren Simon Comprehensive Cancer Center

Shilajit Kundu, MD $\varphi$

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

*Subdoh M. Lele, MD ≠

Fred& Pamela Buffett Cancer Center

Lin Mei,MD‡

Abramson Cancer Center at the University of Pennsylvania

Jeff Michalski, MD, MBA S

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Jeffrey S. Montgomery,MD, MHSA $\_$

University of Michigan Rogel Cancer Center

*Mamta Parikh,MD,MS+

UC Davis Comprehensive Cancer Center

Anthony Patterson,MD 0

St. Jude Children's Research Hospital/The University of Tennessee

Continue

NCCN Guidelines Panel Disclosures

Charles Peyton, MD $\varnothing$

O'Neal Comprehensive Cancer Center at UAB

Elizabeth R. Plimack, MD, MS t p Fox Chase Cancer Center

*Mark A.Preston,MD,MPH 可Dana-Farber/Brigham and Women's Cancer Center

Kyle Richards, MD $\omega $ University of Wisconsin Carbone Cancer Center

*Arlene O. Siefker-Radtke,MD $\dagger$ The University of Texas MD Anderson Cancer Center

*Tyler Stewart, MD ＃UC San Diego Moores Cancer Center

*Debasish Sundi, MD $\omega $ The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute

Matthew Tollefson, MD $\varphi$ Mayo Clinic Comprehensive Cancer Center

Umang Swami, MD, MS †Huntsman Cancer Institute at the University of Utah

Jonathan Tward, MD, PhD §

Huntsman Cancer Institute at the University of Utah

Jonathan L. Wright, MD, MS $\omega $ Fred Hutchinson Cancer Center

NCCN Carly J.Cassara,MSc Lisa Gurski,PhD Bailleie Sliker,PhD

Φ Diagnostic radiology

Φ Diagnostic radiology#Hematology/Hematology oncology

bb Internal medicine

+Medical oncology

Pathology

§Radiotherapy/Radiation oncology

1 Surgery/Surgical oncology

Urology

* Discussion writing committee member

NCCN Guidelines Version 2.2025 Bladder Cancer

Version 2.2025, 10/10/25 © 2025 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.

NCCN Guidelines Index Table of Contents Discussion

NCCN Bladder Cancer Panel Members

Summary of the Guidelines Updates

Bladder Cancer

• Clinical Presentation and Initial Evaluation (BL-1)

• Non-Muscle Invasive or CIS, Primary Evaluation/Surgical Treatment (BL-1)

Risk Stratification of NMIBC (BL-2)

Management per NMIBC Risk Group (BL-3)

Management of Positive Urine Cytology (BL-4)

• Muscle Invasive or Metastatic, Primary Evaluation/Surgical Treatment, Additional Workup (BL-1)Stage II (cT2, N0) Primary and Subsequent Treatment (BL-5)

Stage IIIA (cT3, N0; cT4a, N0; cT1–cT4a, N1) Primary and Subsequent Treatment (BL-7)Stage IIIB (cT1–cT4a, N2,3) Primary and Subsequent Treatment (BL-8)

Stage IVA (cT4b, Any N, M0; Any T, Any N, M1a) Primary and Subsequent Treatment (BL-9)Metastatic Disease, Additional Workup, Primary Treatment (BL-10)

Follow-up, Recurrent, or Persistent Disease (BL-11)

• Principles of Imaging for Bladder/Urothelial Cancer (BL-A)

• Principles of Surgical Management (BL-B)

• Principles of Pathology Management (BL-C)

• Bladder Cancer: Non-Urothelial and Urothelial with Subtype Histology (BL-D)

• Follow-up (BL-E)

• Principles of Instillation Therapy (BL-F)

• Principles of Systemic Therapy (BL-G)

• Principles of Radiation Management of Invasive Disease (BL-H)

• Principles of Alternative Risk Classifiers and Biomarkers (BL-I)

Find an NCCN Member Institution: https://www.nccn.org/home/memberinstitutions.

NCCN Categories of Evidence and Consensus: All recommendations are category 2A unless otherwise

indicated.

See NCCN Categories of Evidence and Consensus.

NCCN Categories of Preference: All recommendations are considered appropriate.

See NCCN Categories of Preference.

The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to

treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2025.

Upper Genitourinary (GU) Tract Tumors

• Renal Pelvis (UTT-1)

• Urothelial Carcinoma of the Ureter (UTT-2)

• Urothelial Carcinoma of the Prostate (UCP-1)

• Primary Carcinoma of the Urethra (PCU-1)

• Staging (ST-1)

• Abbreviations (ABBR-1)

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Updates in Version 1.2025 of the NCCN Guidelines for Bladder Cancer from Version 7.2024 include:

Global

• Language changed: Tis CIS

BL-2

• AUA Risk Stratification for Non-Muscle Invasive Bladder Cancer, High Risk, bullet 2, sub-bullet 1: Variant histologies Certain histopathologic subtypes

• Reference revised: Reproduced Adapted with permission from Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016;196:1021-1029.

• Footnote m revised: Montironi R, et al. Int J Surg Pathol 2005;13:143-153. See aggressive subtype histologies listed on Bladder Cancer: Non-Urothelial and Urothelial with Subytpe Histology (BL-D).

BL-3

• Footnote removed: Valrubicin is approved for BCG-refractory CIS.

BL-4

• Evaluation: If initial positive cytology, consider repeating cytology test within 3 months or If repeated positive cytology,

• Evaluation, sub-bullet 1 added: Repeat cytology within 3 months

• Footnote v added: If enhanced cystoscopy is not readily available, proceed to cystoscopy with bladder biopsies with or without uroscopy.

BL-5

• Primary treatment, statement removed: or TURBT (also for BL-7)

BL-6

• Adjuvant treatment

Sub-sub bullet 2 modified: Consider adjuvant nivolumab or pembrolizumab

Sub-bullet 2 modified: If cisplatin neoadjuvant chemotherapy given and ypT2–ypT4a or ypN+, consider nivolumab or pembrolizumab

BL-8

• Primary treatment: Concurrent chemoradiotherapy pathway removed

• Subsequent treatment modified: Treat as metastatic disease Treat recurrence according to disease stage (BL-10)

• Footnote removed: Principles of Instillation Therapy (BL-F).

• Footnote gg modified: Molecular/genomic testing in a Clinical Laboratory Improvement Amendments (CLIA)- approved laboratory, including FGFR

RGQ RT-PCR for FGFR3 genetic alterations and IHC for HER2 overexpression. See Discussion. See Principles of Alternative Risk Classifiers and

Biomarkers (BL-I). (Also for BL-9 and BL-10)

• Footnote ii added: in the setting of previous complete response, if recurrence, treat according to stage of recurrent disease.

ContinuedUPDATES

Updates in Version 2.2025 of the NCCN Guidelines for Bladder Cancer from Version 1.2025 include:

BL-3

• BCG unresponsive or BCG intolerant pathway, regimen added: Gemcitabine intravesical system (select patients)

• Footnote mm added: Gemcitabine intravesical system may be considered for the treatment of patients with BCG-unresponsive NMIBC with CIS (with or without papillary) tumors.

• Footnote nn added: Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV pembrolizumab. Pembrolizumab

and berahyaluronidase alfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.

BL-G 1 of 7

• Bullet added: Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV pembrolizumab. Pembrolizumab and

berahyaluronidase alfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.(Also for BL-G 2 of 7 and BL-G 3 of 7)

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

UPDATES

BL-A 3 of 5

• Follow-up, sub-bullet 1 modified: Upper tract and abdomen/pelvis imaging with contrast as defined previously at 3- to 6-month intervals for 2 years, then abdomen/pelvis imaging with contrast annually for up to 5 years and as indicated thereafter.

BL-B 2 of 4

• Radical Cystectomy/Cystoprostatectomy, bullet 1 modified: In non–muscle-invasive disease, radical cystectomy is generally reserved for residual highgrade cT1, subtype histology aggressive histopathologic subtypes, lymphovascular invasion, concomitant CIS, and BCG-unresponsive disease (see

Bladder Cancer: Non-Urothelial and Urothelial with Subtype Histology [BL-D]).

BL-B 4 of 4

• Percutaneous or ureteroscopic surgical procedures, sub-bullet 3 modified: Laser therapies (Nd:YAG – penetration 4–6 mm; Ho:YAG – shallow penetration<0.5 mm)

• Bullet 7 modified: Topical immunotherapy and chemotherapy management (see Principles of Instillation Therapy [BL-F 3 of 4] for more information).• Bullets removed (added to BL-F 3 of 4):

BCG, mitomycin

Route of administration might include percutaneous antegrade (preferred) or retrograde ureteral catheters

Induction and maintenance therapy regimens, similar to intravesical therapy, can be used

BL-D 1 of 2

• Page has been extensively modified

BL-E 1 of 6

• Table 1, High Risk, very high risk features, bullet modified: Variant histologies Certain histopathologic subtypes

• Footnotes removed:

Abdominal/pelvic imaging include CT or MRI.

Principles of Imaging for Bladder/Urothelial Cancer

• Footnotes modified:

Upper tract imaging includes CTU, MRU, intravenous pyelogram (IVP), retrograde pyelography, or ureteroscopy. Principles of Imaging for Bladder/

Urothelial Cancer (BL-A).

Montironi R, et al. Int J Surg Pathol 2005;13:143-153. See Principles of Pathology (BL-D 1 of 2)

BL-E 3 of 6

• Blood tests, year 2-5, bullet 3 modified: B12 annually based on clinical judgment (also for BL-E 4 of 6)• Blood tests, year 5-10 and >10: B12 annually based on clinical judgment (also for BL-E 4 of 6)• Urine tests, year 1, bullet 1 modified: Consider urine cytology every 6–12 mo (also for BL-E 4 of 6)

BL-E 6 of 6

• Blood tests, bullet 2 modified: B12 annually for patients who had undergone a cystectomy based on clinical judgment

BL-F 3 of 4

• Topical or Percutaneous Administration of Chemotherapy or BCG

Bullet added: Topical immunotherapy and chemotherapy management

Sub-bullet added: BCG, mitomycin

Sub-bullet added: Route of administration might include percutaneous antegrade (preferred) or retrograde ureteral catheters

Sub-bullet added: Induction and maintenance therapy regimens, similar to intravesical therapy, can be used

BL-G

• Section extensively modified

BL-I

• Section new to Guidelines

UTT-1

• Primary treatment, low grade: Endoscopic resection ± postsurgical intrapelvic chemotherapy or BCG

Updates in Version 1.2025 of the NCCN Guidelines for Bladder Cancer from Version 7.2024 include:

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

![CLINICAL PRESENTATION EVALUATIONa\nPRIMARY EVALUATION/SURGICAL TREATMENT\nPRESUMPTIVE CLINICALA CLINICALB R1P\nADDITIONAL STAGINGWORKUP\nSTAGEf,9\nNon-muscle-invasive bladder cancer(NMIBC)cisternia(EUA)(bimanual)\nTURBtd\nNon-muscle-invasive bladder cancer(NMIBC)cisternia\nCIS\nStage II(cT2, N0)h\nBL-5\nStage IIIIA (cT3, N0;cT4a,N0;cT1-T4a,N1)'h\nStepive LIEB\nBL-7\nStage IIIIB (cT1-T4a,N2,3)h\nBl-8\nStage III\nStepive LIEB\nMetastatic(Stage IVB Any T, Any N, M1b)\nBL-10\nPransse\nPRESUMPTIVE CLINICALA CLINICALB R1P\nStage II4(cT3, N0;cT4a,N0;cT1-T4a,N1)'h\nBl-8\nStage III\nStepive LIEB (cT3, N0;cT4a,N0;cT1-T4a,N1)'h\nBl-8\nPPT4d\nStage II(BL-5\nPPT6\nStage III(ICT4, N0);\nStage III\nStage III\nStage III\nPPT8\nMetastatic(Stage IVB Any T, Any N, M1b)\nBL-8\n10\nAV\nAT.7\nAV\nNY1)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure1bce392d4b624eb0a1dc90461907b459_0_4.png) aFor tools to aid optimal assessment and comprehensive care of older adults with cancer, see NCCN Guidelines for Older Adult Oncology.

b NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric-Criteria for the Evaluation of Lynch Syndrome Based on Personal or Family History of Cancer.

c Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

d Principles of Surgical Management(BL-B).

eImmediate intravesical chemotherapy reduces the recurrence rate by 35% for selected patients. Most efficacious in patients with low-grade, low-volume Ta urothelial cancer. Post-TURBT intravesical chemotherapy should not be utilized if concern for bladder perforation. See Principles of Instillation Therapy(BL-F).

Principles of Pathology Management(BL-C).

9Bladder Cancer: Non-Urothelial and Urothelial with Subtype Histology(BL-D).

The modifier "c" refers to clinical staging based on bimanual EUA, endoscopic surgery (biopsy or transurethral resection [TUR]), and imaging studies. The modifier "p" refers to pathologic staging based on cystectomy and lymph node dissection.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Non-Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

RISK STRATIFICATION OF NMIBC

![Initial TURBT shows NMIBC or Visually complete resection\nVisually complete resection\nHigh-grade NMIBC\nHigh-grade NMIBC and JAL\nCarcinoma in situ(CIS) or Tai\nCarcinoma in NMCIB\nT1 or consider for select Taj\nResidual NMIBC\nor no residual cancer\nVisually incomplete resection\nHigh-volume tumorii\n](2/aj0YEe4oUhYkBdfpda0fYP/figure6decc2e9b4d84855b33ac25d6fb609c5_0_5.png) AUA Risk Stratification for Non-Muscle-Invasive Bladder Cancer*

|Low Risk|Intermediate Risk|High Risk| |---|---|---| |● Papillary urothelial neoplasm of low malignant potential ● Low grade urothelial carcinoma ● Ta and ●≤3cm and Solitary|● Low grade urothelial carcinoma ●T1 or >3 cm or Multifocal or Recurrence within 1 year ● High grade urothelial carcinoma ● Ta and ≤3cm and Solitary|● High grade urothelial carcinoma ● CIS or T1 or >3cm or Multifocal or Multifocal ● High grade urothelial carcinoma ● Very high risk features (any): BCG unresponsive = Certain histopathologic subtypes m Lymphovascular invasion -Prostatic urethral invasion|

Adapted with permission from Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016;196:1021-1029.

*Within each of these risk strata an individual patient may have more or fewer concerning features that can influence care.

i High-volume tumors(large or highly multifocal) are at high risk of residual tumor.

Consider repeat TURBT for high-grade Ta particularly if large, and/or no muscle in specimen.

k Muscle should be present in repeat TURBT pathology specimen if possible.

${}^{1}$ Kamat AM,et al.J Clin Oncol 2016;34:1935-1944.

m See aggressive subtype histologies listed on Bladder Cancer: Non-Urothelial and Urothelial with Subtype Histology(BL-D).

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Non-Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

MANAGEMENT PER NMIBC RISK GROUP

![AUA RISK GROUP (BL-2)\nLow\nIntermediate\n\nIntravesical therapy P,q (preferred)\nprferred)\nor (Surveillance\nCystectomy (preferred)\nBacillus Calmette-Guérin (BCG) naive\nHigh\nBacillus Calmette-Guérin (BCG) naive\nRisk features\nNo very-high-risk features\nVery-high-risk Nocableprint's\nNocystectomy (preferred)\nBCGG Pystectomy 1, preferred)\nHigh\nCystectomy (preferred)\nIntravesical chemotherapyP or or or Surveillance\nCystoscopy negative\nBL-4\nBL-4\nALA Risk and Group and manage accordingly\n\nBBCG unresponsive\nBCG intolerant\nNodofaragene firadenove-cvng (select patients)t\nor\nNogapendekin alfa inbakicept-pmln + BCGU (select patients)s\n\nBembrolizumab (select patients)s,nn\nNodafaragene firadenove-cvng (select patients)t\nPembrolizumab (select patients)s,nn\n](2/aj0YEe4oUhYkBdfpda0fYP/figureeaa85531530949c793fb24171f01c0e6_0_5.png) nLymphovascular invasion, prostatic urethral involvement of tumor, subtype histology (eg,micropapillary, plasmacytoid, sarcomatoid).

0 Should consider single perioperative instillation of intravenous chemotherapy at time of TURBT.

P Principles of Instillation Therapy(BL-F).

9 Options for intravesical therapy for intermediate-risk disease include BCG and chemotherapy;should consider BCG availability in decision-making.

If not a cystectomy candidate, and recurrence is high-grade cTa or cT1, consider concurrent chemoradiotherapy(category 2B for cTa, category 2A for cT1) or a clinical trial. See Principles of Systemic Therapy(BL-G 5 of 7).

S Pembrolizumab may be considered for the treatment of patients with BCG-unresponsive, high-risk NMIBC with CIS(with or without papillary) tumors(category 2A) or with BCG-unresponsive, high-risk NMIBC with high-grade papillary Ta/T1 only tumors without CIS(category 2B) who are ineligible for or have elected not to undergo cystectomy.

t Nadofaragene firadenov-vcng may be considered for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with CIS (with or without papillary) (category 2A) or with BCG-unresponsive, high-risk, NMIBC with high-grade papillary Ta/T1 only tumors without CIS (category 2B).

uNogapendekin alfa inbakicept-pmln in combination with BCG may be considered for the treatment of patients with BCG-unresponsive, high-risk NMIBC in with CIS(with or without papillary) tumors.

mm Gemcitabine intravesical system may be considered for the treatment of patients with BCG-unresponsive NMIBC with CIS(with or without papillary) tumors.

nn Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV pembrolizumab. Pembrolizumab and berahyaluronidase inalfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Management of Positive Urine Cytology

NCCN Guidelines Index Table of Contents Discussion

![RECURRENT OR PERSISTENT DISEASE FOLLOW-UP RESULTS\nEVALUATION\nPERSISTENT DISEASE FOLLOW-UP RESULTS RESULTS\nCancer\nConsider:\nRepeat cytology within 3 months\nSelected mapping biopsies\nincluding transurethral biopsy of\nprostate\nBladder positive\nProstate positive\nReclassify AUA Risk Group and manage accordingly (BL-3)\nII(1-251-4000-254000-253000-268000-240000-2711\nClystology\nInaging negative\nUreteroscopy\nEnhanced cystoscopy\nv(if available)\nNon-urinary tract source (eg, vagina, cervix, rectum) and\nreferral to gynecology or other specialist, as appropriate\nUpper tract positive\nUrothelial Carcinoma of the Prostate(UCP-1)\nUpper tract tract DUTT Tumors\n(UTT-1)\n](2/aj0YEe4oUhYkBdfpda0fYP/figurea89774be8ce548b7b7ff4f5ab21c334a_0_4.png) d Principles of Surgical Management(BL-B).

P Principles of Instillation Therapy(BL-F).

vIf enhanced cystoscopy is not readily available, proceed to cystoscopy with bladder biopsies with or without uroscopy.

w Follow-up(BL-E).

Note: All recommendations are category 2A unless otherwise indicated.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

![CLINICAL ADDITIONAL STAGINGh WORKUPc\nReoadjuvant cisplatin-based combination chemotherapy^{2} or perioperative/sandwich immunotherapy and with neoadjuvant cisplatin-based combination chemotherapy^{2} followed by radical cystectomyd2 (category 1)\nAbdomen/pelvis CT or MRI if not previously done\nBone scan or MRIX if clinical suspicion or symptoms of bone metastases\nEstimate glomerular filtration rate (GFR) to assess eligibility for cisplatinY\nOr\nReassess tormative therapy or Bladder deflection\nChodder preservation with concurrent chemotherapyua,bb,cc (category)\nIf cis, Ta, or T1, consider TURBT +/-intravesical therapyplab\ncansy thorted population\nAsdujant-treatment\nAdjuvant Treatment (BL-6)\nAdjuvant Treatment (BL-6)\nAddujant Treatment (BL-6)\nAddujant Treatment (BL-6)\nTumor\nTumor\nFor Cystectomy alone for those not eligible to receive cisplatin-based chemotherapy or Bladder preservation\nAAdjuvant therapyaa,bb,cc (category)\nReassess tumor status 2-3 months treatment 1) and maximal TURBT\nIf patient is not a candidate for cystectomy or definitive chemoradiotherapy: RTbb\nAsdujant\nTothemol\nAdoujum\nRassess tumor status 2-3 months after treatment completionbb\nTumor\nAsdujumou\nTothemol\nRassess tumor on highly selected cases)'\nTreat as metastatic disease (BL-10)\nFollow-up(BL-E)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure18eca76e44354806be5bc60deb3319ef_0_4.png) Note: All recommendations are category 2A unless otherwise indicated.

Footnotes on BL-6

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

ADJUVANT TREATMENT

![If gemcitabine + cisplatin + durvalumab given preoperatively, then durvalumab should be used postoperatively.\n● Based on pathologic risk,\nIf no cisplatin neoadjuvant treatment given and pT3, pT4a, or pN+\n● Adjuvant cisplatin-based chemotherapy should be discussed (preferred)zor\n● Consider adjuvant nivolumabee or pembrolizumabz,ee\nor\nIf cisplatin neoadjuvant chemotherapy given and ypT2-ypT4a or ypn+,\nConsider nivolumabe ee or pembrolizumabz,ee\n)\nConsider adjuvant RT in selected patients (pT3-4, positive nodes/margins at the time of surgery)bb (category 2B)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure62b3898ca64246f693a6f296821fad19_0_5.png) ${}^{c}$ Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

dPrinciples of Surgical Management(BL-B).

h The modifier "c" refers to clinical staging based on bimanual EUA, endoscopic surgery (biopsy or TUR), and imaging studies. The modifier "p" refers to pathologic staging based on cystectomy and lymph node dissection.

P Principles of Instillation Therapy(BL-F).

Consider FDG-PET/CT scan (skull base to mid-thigh) (category 2B).

yFor patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin.

z Principles of Systemic Therapy(BL-G 1 of 7).

a Principles of Systemic Therapy (BL-G 5 of 7).

bb Principles of Radiation Management of Invasive Disease(BL-H).

cc Optimal candidates for bladder preservation with chemoradiotherapy include patients with tumors that present without moderate/severe hydronephrosis,are without concurrent extensive or multifocal CIS, and are <6 cm. Ideally,tumors should allow for a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-H).

dd Principles of Systemic Therapy (BL-G 2 of 7).

ee Most appropriate for patients who value an opportunity to delay recurrence even if the chance of cure was not improved, and for whom the risk of side effects was acceptable.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

![CLINICAL STAGING^{\hbar} 440N& WORKUPc\nADdejuvant cisplatin-based combination chemotherapy^{\circ} or perioperative/sandwich immunotherapy with neoadjuvant cisplatin-based combination chemotherapy^{\circ} 2 or plus inseted cisplatin-based combination chemotherapy^{\circ} 2 for related by radical cystectomyd,ff (category 1)\nAdjuvant Treatment (BL-6)\nOR\nPachasing CTCT 49 of bone metastases\nSusps\n●Estimate GFR to assess eligibility\nFor patient is not a candidate for cystectomy or definitive\nFor patient is not chemoradiotherapy:RT^{\circ} \nO\nPachasing CTCT 49 of bone metastases\n●Estimate GFR to for cisplatin\n\nAcc.8\nNCCN\nNational Guidelines Version 2.2025\nNCCN\nNCCN\nCancer-Invasive Bladder Cancer\nMuscle-Invasive Bladder Cancer\nSTAGING^{\circ} 440N& WORK\nAbdovular cisplatin-based chemotherapy^{\circ} 2 for different clinical therapy\n●9\nAschologres 49 of bone metastases\n●Estimate GFR to assess eligibility\nFor patient is not a candidate for cystectomy or definitive\n●9\nCystectomy for derivative\nFor patient\nRBT\nTURB± intravesimal therapy\n●3\nDustginal\nPprinciples of Imaging for Bladder/Urothelial Cancer (BL-A)\nThe modifier "c" refers to clinical staging based on bimanual EUA, endoscopic surgery (biopsy or TUR), and imaging studies. The modifier "p" refers to pathologic staging based on cystectomy and lymph node dissection. \nAC \nOptimal candidates for bladder preservation at with chemoradiotherapy include: Co 2B). \nFor patients with borderline Therapy (BL-F). 2\nXConsider FDG-PET/CT scan (skull base to mid-thigh) (category 2B). \nYFor patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin. \n2Principles of Systemic Therapy (BL-G 1 of 7).\n2Principles of Systemic Therapy (BL-G 1 of 7).\nPrinciples of Systemic Therapy (BL-G 2 of 7).\nPrinciples of Systemic Therapy and have a response factor 2B.\nProinciples of Systemic Therapy (BL-G 2 of 7).\nPrinciples of Systemic Therapy and have a response factor 2B.\nReessess tumor status completion bb\n■\n■Surveillance\nNo tumor tumor\n■\n|Surveillance\n■Systemic therapy^# 2-3 months after treatment\n■Systemic therapy^# 2B.\n■TURB± intravavesical therapy^# 0\n■TURB+ intravavesical therapy^# 2B.\nBest supportive care (NCCN Guidelines for Palliative Care)\n■Optimal candidates for bladder preservation with chemoradiotherapy include: Co 2B.\npatients with tumors that present without moderate/severe hydronephrosis, are without concurrent extensive or multifocal CIS, and are <6 cm. Ideally, tumors should allow a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-G 2 of 7).\n3\nReport Vortical Therapy p2\nTop-RURB± intravavesical therapy^# 2B.\nBest supportive care (NCCN Guidelines for Palliative Care)\nOptimal candidates for bladder preservation with chemoradiotherapy include: Co 2B.\nwithout concurrent extensive or multifocal CIS, and are <6 cm. Ideally, tumors should allow a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-H).\n3\nFollow-up(BL-E)\nIn the following literature 2.2025, 10/10/25 @ 2025 National Comprehensive Cancer Network® (NCCN"), All rights reserved.\nR\n](2/aj0YEe4oUhYkBdfpda0fYP/figuree901aa9989de412da2e7f56eaf6a9315_0_4.png) d Principles of Surgical Management(BL-B).

P Principles of Instillation Therapy(BL-F).

Consider FDG-PET/CT scan (skull base to mid-thigh) (category 2B).For patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin.

z Principles of Systemic Therapy(BL-G 1 of 7).

aa Principles of Systemic Therapy (BL-G 5 of 7).

bb Principles of Radiation Management of Invasive Disease(BL-H).

${}^{cc}$ Optimal candidates for bladder preservation with chemoradiotherapy include patients with tumors that present without moderate/severe hydronephrosis, are without concurrent extensive or multifocal CIS, and are $<6 ~cm$. Ideally, tumors should allow a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-H).

dd Principles of Systemic Therapy (BL-G 2 of 7).

ff Patients with cN1 disease have better outcomes if they are given neoadjuvant chemotherapy and have a response.

Persistent Disease(BL-11)

![National Comprehensive Cancer Network®\n](2/aj0YEe4oUhYkBdfpda0fYP/figure0ec99917e500491a9d24f8bdc12e3964_0_1.png)

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

![CLINICAL STAGINGh WORKUP^{C}\nADDITIONAL WORKUP^{C}\nPREMIARYTREATMENT\n DOWNED\nSystemedgammadd\nAdbodomen/Pelvis CT or MRI*if not previously done\nSystaciony#if non\nMRI*if not previously previously done\nSystaciony#if non\nPriKINGH\nAbdomen/Pelvis CT or MRI*if\nSystemic therapydd\nComplete response\nConsolidation cystectomy\nConsolidation chemoradiotherapyaa,bb\nor\nFollow-up(BL-E)\nRovance24\nProgression→ Treat as metastatic disease (BL-10)\n](2/aj0YEe4oUhYkBdfpda0fYP/figurec06f6ae69725441e94fa188caa7e47ce_0_4.png) ![\nAbdomen/pelvis CT or MRI× if not previously done\n\nCT1- cT4a,N2,3)\n\nSymptoms\nb Principles of Radiation Management of Invasive DIREngability\n\nPartial response\nCystectomy“aa,bb\nConsolidation cystectomy\nConsolidation or chemoradiotherapyaa,bb\nor\nor Surveillance\nFollow-up\nPartial response\nCystectomy or Chemoradiotherapyaa,bb\n\nDLI-E)\nFollow-up BLICE 8(BL-E)\nAbdomen/pelvis CT or membrane\nStatus 2-3\nmonths after treatmenth\nd treatmenth\nProgression → Treat as metastatic disease (BL-10)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure3cdb0ba95ddb4d30b47d579d35000ad1_0_5.png) C Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

d Principles of Surgical Management(BL-B).

h The modifier "c" refers to clinical staging based on bimanual EUA, endoscopic surgery(biopsy or TUR), and imaging studies. The modifier "p" refers to pathologic staging based on cystectomy and lymph node dissection.

Consider five etalization for cisplatin.

y For patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin.

aa Principles of Systemic Therapy(BL-G 5 of 7).

bb Principles of Radiation Management of Invasive Disease(BL-H).

dd Principles of Systemic Therapy (BL-G 2 of 7).

99 See Principles of Alternative Risk Classifiers and Biomarkers (BL-I).

hh Imaging with CT of chest/abdomen/pelvis with contrast. If there is no evidence of distant disease on imaging reassessment, further cystoscopic assessment of tumor response in the bladder may be considered.

${}^{i}$ In the setting of previous complete response, if recurrence, treat according to stage of recurrent disease.

![Recurrent or Persistent\nDisease(BL-11)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure132d820b9f394bbaa8f5d60e0b345bb6_0_17.png) NCCN授权医脉通提供NCCN指南全文下载。wmIsyy于2025/10/21,23:32在医脉通平台下载，仅供个人使用，严禁分发。2025美国国家综合癌症网络版权所有。

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

![CLINICAL STAGINGh\nADDITIONAL WORKUPC\n PRIMARY TREATMENT\n No tumor\nAfter 2-3 cycles, reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy\nNo tumor\nChemoradio- and/or\nFollow-up\nFollow-up\n(BL-E)\nADdomen/pelvis CT or MRI× not previously done ● Chest imaging (CT chest)\nMONO disease\nM0 disease\nConcurrent chemoradiotherapyaa,bb\n32\nNo tumor\nAfter 2-3 cycles, reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy\nTo assess using imaging\nM1a disease → Systemic therapydd\nSystemic therapydd and imaging of abdomen/pelvisc\nTumor\nNon to 23 - cycles, reassess with reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy\nTo 23 32 433.19\nSystemic therapydd and imaging of abdomen/pelvisc\nM1a disease →Systemic therapydd and imaging of abdomen/pelvis cystoscopy\nTo 23 32 433.19\nSystemic therapydd and imaging of common periodic therapy\nFollow-up\nPUE (BL-E)\n](2/aj0YEe4oUhYkBdfpda0fYP/figurefa9493e50008486f810313681b9ff95e_0_4.png) ${}^{c}$ Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

dPrinciples of Surgical Management(BL-B).

× Consider FDG-PET/CT scan (skull base to mid-thigh) (category 2B).

y For patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin.

aa Principles of Systemic Therapy (BL-G 5 of 7).

bb Principles of Radiation Management of Invasive Disease(BL-H).

dd Principles of Systemic Therapy (BL-G 2 of 7).

99 See Principles of Alternative Risk Classifiers and Biomarkers (BL-I).

ii Non-bulky disease and no significant clinical progression.

kk See Principles of Systemic Therapy (BL-G 3 of 7 and 4 of 7).

Recurrent or Persistent Disease(BL-11)

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

CLINICAL STAGINGh

ADDITIONAL WORKUPC

PRIMARY TREATMENT

![\nBone scan or MRI if clinical suspicion\nor symptoms of bone metastases\nChest CT\nConsider central nervous system\nCNS) imagingC\nEstimate GFR to assess eligibility for cisplatin\n|Systemic therapy dd,kk\nd/or\nPalliative RTbb\nFollow-up\nPalliative\nBL-E)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure569ba4cf6c6f4025b5a7844798b23c74_0_7.png) •Consider biopsy if technically feasible

● Molecular/genomic testing99

dd Principles of Systemic Therapy(BL-G 2 of 7).

99 See Principles of Alternative Risk Classifiers and Biomarkers (BL-I).

kk See Principles of Systemic Therapy (BL-G 3 of 7 and 4 of 7).

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

FOLLOW-UPC

RECURRENT OR PERSISTENT DISEASE

TREATMENT OF RECURRENT OR PERSISTENT DISEASE

![Muscle invasive or selected metastatic disease treated with curative intent\nFollow-up(BL-E)\nPreserved bladder\nCytology positive\nImaging negative\nCystoscopy\nnegative\nMetastatic or local recurrence\nlocal recurrence\npostcystectomy\nBL-10\nppr#\ncc|Systectomy\nppr#Cystectomy\nR104\nNo\nCystectomy,d,w\nnn1\nro|Bodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\nLodder\n\n](2/aj0YEe4oUhYkBdfpda0fYP/figurea4f139b8d7004232952c3d7fce8de0e4_0_7.png) cPrinciples of Imaging for Bladder/Urothelial Cancer(BL-A).

dPrinciples of Surgical Management(BL-B).

P Principles of Instillation Therapy(BL-F).

w Follow-Up(BL-E).

aa Principles of Systemic Therapy (BL-G 5 of 7).

bb Principles of Radiation Management of Invasive Disease(BL-H).

dd Principles of Systemic Therapy (BL-G 2 of 7).

kk See Principles of Systemic Therapy (BL-G 3 of 7 and 4 of 7).

If not a cystectomy candidate, consider concurrent chemoradiotherapy (BL-G 5 of Z)(if no prior RT), change in intravesical agent, or a clinical trial.

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-A 1 OF 5

PRINCIPLES OF IMAGING FOR BLADDER/UROTHELIAL CANCER

No single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient

requirements, and may be extended beyond 5 years after shared decision-making between the patient and physician.

Non–Muscle-Invasive Bladder Cancer (NMIBC)

Chest Imaging

• Staging:

Chest imaging may not be necessary in initial staging of noninvasive disease.

• Follow-up of NMIBC:

Routine chest imaging is not recommended.1

Abdomen and Pelvis Imaging

• Staging:

CT urography (CTU) (CT of the abdomen and pelvis without and with intravenous (IV) contrast with excretory imaging).

MR urography (MRU) may be appropriate, especially in patients with poor renal function or iodinated contrast allergy but with GFR >30

and no acute renal failure. May be performed without gadolinium-based contrast utilizing T2 imaging and native image contrast to evaluate

upper tracts. Will have decreased sensitivity to plaque-like or non-obstructive lesions and metastasis.

Renal ultrasound (US) or CT without contrast may be utilized in conjunction with retrograde ureteropyelography in patients who cannot

receive either iodinated or gadolinium-based contrast material.

Consider: In sessile or high-grade tumors, MRI of the pelvis without and with IV contrast for local staging.

◊ May be performed in addition to CTU.

◊ Can be performed without contrast if renal function does not allow for contrast administration, as early data suggest T2 and diffusionweighted images may help with local staging.2,3

• Follow-up of NMIBC: (BL-E)

Upper tract (CTU, MRU, IV pyelogram [IVP], or retrograde ureteropyelography with CT or US, or ureteroscopy) and abdomen/pelvis imaging

at baseline. For patients with high-risk NMIBC, upper tract imaging also should be performed at 12 months and every 1–2 years thereafter

up to 10 years.

Evaluation for Suspected Bone Metastasis

• Bone imaging not generally recommended as bone metastasis is unlikely.

Neurologic/Brain Imaging4,5

• Staging:

Brain MRI not generally recommended.

Continued References

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-A 2 OF 5 Continued

References No single follow-up plan is appropriate for all patients. Follow-up frequency and duration should be individualized based on patient

requirements, and may be extended beyond 5 years after shared decision-making between the patient and physician.

Muscle-Invasive Bladder Cancer (MIBC)

Chest Imaging

• Staging4:

CT of the chest with or without contrast (preferred)6

Posteroanterior (PA) and lateral chest x-ray

FDG-PET/CT (category 2B) may be beneficial in selected patients with T2 (muscle-invasive disease) and in patients with ≥cT3 disease. This

will also include abdomen and pelvis if performed.7-10 FDG-PET/CT should not be used to delineate the anatomy of the upper urinary tract.

• Follow-up with or without cystectomy: (BL-E)

Chest CT with or without IV contrast (preferred)

◊ May be performed without contrast if IV contrast cannot be given.

◊ Consider performing with the abdomen and pelvis for a single exam in patients who also need imaging of the abdomen and pelvis.

PA and lateral chest x-ray

FDG-PET/CT (category 2B) may be performed if not previously done or if metastasis is suspected in selected patients. This examination

will also include the abdomen and pelvis. FDG-PET/CT should not be used to delineate the anatomy of the upper urinary tract.

• Follow-up of cT4b (BL-E) and metastatic disease:

Chest CT with or without IV contrast (preferred)

◊ May be performed without contrast if IV contrast cannot be given.

◊ Consider performing with the abdomen and pelvis for a single exam in patients who also need imaging of the abdomen and pelvis.

PA and lateral chest x-ray

FDG-PET/CT (category 2B) may be performed if not previously done or in patients with high-risk MIBC in whom metastatic disease is

suspected. This could also be used to guide biopsy in certain patients. FDG-PET/CT should not be used to delineate the anatomy of the

upper urinary tract.

PRINCIPLES OF IMAGING FOR BLADDER/UROTHELIAL CANCER

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-A 3 OF 5

Muscle-Invasive Bladder Cancer (continued)

Abdomen and Pelvis Imaging

• Staging:

CTU (CT of the abdomen and pelvis without and with IV contrast with excretory imaging).11

MRU may be appropriate in patients with poor renal function or iodinated contrast allergy but with GFR >30 and no acute renal failure.

Renal US and CT without contrast (particularly when FDG-PET/CT is not utilized) may be utilized in conjunction with retrograde evaluation

in patients who cannot receive either iodinated or gadolinium-based contrast material.

Ureteroscopy if suspected upper tract lesions.

FDG-PET/CT (category 2B) may be useful in selected patients with ≥cT2 disease and may change treatment in patients with ≥cT3 disease.1

FDG-PET/CT should not be used to delineate the anatomy of the upper urinary tract.

CT or MRI of the abdomen and pelvis with IV contrast if not performed with initial evaluation.

MRI of the pelvis without and with IV contrast for local staging.

◊ May be performed in addition to CTU.

◊ May also be performed without contrast if there is a contraindication to contrast.1

• Follow-up (BL-E):

Upper tract and abdomen/pelvis imaging with contrast as defined previously at 3- to 6-month intervals for 2 years, then abdomen/pelvis

imaging with contrast annually for up to 5 years and as indicated thereafter.

FDG-PET/CT (category 2B) may be performed if not previously done or in patients with high-risk MIBC in whom metastatic disease is

suspected. This could also be used to guide biopsy in certain patients. FDG-PET/CT should not be used to delineate the anatomy of the

upper urinary tract.

Evaluation for Suspected Bone Metastasis

• Symptomatic, or patients at high risk, or those with laboratory indicators of bone metastasis may be imaged with MRI, FDG-PET/CT (category 2B), or bone scan. FDG-PET/CT (category 2B) may also be considered in cases when additional sites of extraosseous metastatic disease are suspected or previously documented.

Metastatic Disease - Patients Being Observed

• See Follow-Up (BL-E 6 of 6)

Neurologic/Brain Imaging4,5

• Staging

Brain MRI without and with IV contrast is recommended only in symptomatic or selected patients at “high risk” (eg, small cell histology) .

CT with IV contrast is considered only when symptomatic patients cannot undergo MRI (ie, non-MRI–compatible cardiac pacer, implant or

foreign body, end-stage renal disease).

Continued References PRINCIPLES OF IMAGING FOR BLADDER/UROTHELIAL CANCER

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-A 4 OF 5 References

Upper Tract (renal pelvis and urothelial carcinoma of the ureter)12

• Staging and follow-up of ≤T1 disease (see recommendations for NMIBC bladder cancer).

• Staging and follow-up of ≥T2 disease (see recommendations for MIBC bladder cancer).

Urothelial Carcinoma of the Prostate/Primary Carcinoma of the Urethra

• Staging:

Chest CT (preferred) or PA and lateral chest x-ray.

Consider abdomen CT or MRI in high-risk T1 disease or patients with ≥T2 disease.13

MRI of the pelvis without and with IV contrast for local staging.

• Additional staging if urothelial carcinoma of prostate:

Imaging of upper tracts and collecting system.

CTU (CT of the abdomen and pelvis without and with IV contrast with excretory imaging).

MRU may be appropriate in patients with poor renal function or iodinated contrast allergy but with GFR >30 and no acute renal failure.

Ureteroscopy

Renal US or CT without contrast may be utilized in conjunction with retrograde evaluation in patients who cannot receive either iodinated

or gadolinium-based contrast material.

• Additional staging if primary carcinoma of the urethra:

In the setting of palpable inguinal lymph nodes:

◊ Biopsy of palpable nodes.

◊ CT of the chest, abdomen, and pelvis for additional staging, if not yet performed.

• Follow-up:

Low-risk T1 or <T1 disease:

◊ MRI or CT of pelvis with and without IV contrast.

High-risk T1 or ≥T2:

◊ May consider more extensive follow-up based on risk factors; 3–6 months for 2 years and then yearly.

– Chest imaging with x-ray and/or CT as previously discussed.

– Imaging of abdomen and pelvis with MRI or CT with and without contrast.

PRINCIPLES OF IMAGING FOR BLADDER/UROTHELIAL CANCER

Note: All recommendations are category 2A unless otherwise indicated. NCCN Guidelines Index Table of Contents Discussion 5 OF 5 PRINCIPLES OF IMAGING FOR BLADDER/UROTHELIAL CANCER REFERENCES

Abstract

Fluorodeoxyglucose -positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy.

References

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-B 1 OF 4

PRINCIPLES OF SURGICAL MANAGEMENT

TURBT for Staging

• Adequate resection with muscle in specimen

Muscle may be omitted in cases of documented low-grade Ta disease

In cases of suspected or known CIS:

◊ Biopsy adjacent to papillary tumor

◊ Consider prostate urethral biopsy

Papillary appearing tumor (likely non-muscle invasive)

◊ Early repeat TURBT (within 6 weeks) if:

– Incomplete initial resection

– No muscle in original specimen for high-grade disease

– Large (≥3 cm) or multifocal lesions

– Any T1 lesion

Transurethral resection (TUR) for sessile or invasive appearing tumor (likely muscle invasive)

◊ Repeat TURBT if:

– Prior resection did not include muscle in the setting of high-grade disease

– Any T1 lesion

– First resection does not allow adequate staging/attribution of risk for treatment selection

– Incomplete resection and considering tri-modality bladder preservation therapy

• Enhanced (blue light and narrow-band imaging) cystoscopy may be helpful in identifying lesions not visible using white light cystoscopy.

TURBT/Maximal TURBT for Treatment

• Maximally complete and safe TURBT is an essential part of bladder preservation. See Principles of Radiation Therapy (BL-H).

• TURBT alone can be considered for non-cystectomy candidates.

• A visually complete TURBT is associated with improved patient outcomes in non-metastatic settings.

Continued

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-B 2 OF 4

Transurethral Resection of the Prostate (TURP)

• Primary treatment option for urothelial carcinoma of the prostate with ductal/acini or prostatic urethral pathology.

• Postsurgical intravesical BCG is recommended (Principles of Instillation Therapy [BL-F]).

TUR of the Urethral Tumor

• Primary treatment of CIS, Ta, T1 primary carcinoma of the urethra.

• Patients with a prior radical cystectomy and a cutaneous diversion should consider a total urethrectomy.

• Consider postsurgical intraurethral therapy (Principles of Instillation Therapy [BL-F]).

Partial Cystectomy

• May be used for cT2 muscle-invasive disease with solitary lesion in location amenable to segmental resection with adequate margins, in

appropriately selected patients. May also be appropriate in other select situations including cancer in a bladder diverticulum.

• No CIS as determined by random biopsies.

• Bilateral pelvic lymphadenectomy should be performed.

Radical Cystectomy/Cystoprostatectomy

• In non–muscle-invasive disease, radical cystectomy is generally reserved for residual high-grade cT1, aggressive histopathologic subtypes,lymphovascular invasion, concomitant CIS, and BCG-unresponsive disease (Bladder Cancer: Non-Urothelial and Urothelial with Subtype

Histology [BL-D]).

• Cystectomy should be done within 3 months of diagnosis if no therapy is given.

• Primary treatment option for cT2, cT3, and cT4a disease. Highly select patients with cT4b disease that responds to primary treatment may be eligible for cystectomy.

• Bilateral pelvic lymphadenectomy should be performed.

• In appropriately selected patients, approaches that preserve the uterus, vagina, and/or ovaries should be employed when feasible.

Radical Nephroureterectomy with Cuff of Bladder

• Primary treatment option for non-metastatic high-grade upper GU tract tumors.

Continued

PRINCIPLES OF SURGICAL MANAGEMENT

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-B 3 OF 4

Regional Lymphadenectomy

• Endoscopic lymph node dissections should be equivalent to open dissection.

• For bladder, recommend pelvic lymph node dissection; for upper tract recommend regional lymph node dissection for high-grade tumors.

Urethrectomy

• Distal urethrectomy may include inguinal lymph node dissection in selected cases.

• Total urethrectomy may include inguinal lymphadenectomy in selected cases.

• Male patients with T2 primary carcinoma of the urethra in the bulbar urethra may be treated with a urethrectomy with or without a

cystoprostatectomy.

• Male patients

with T2 primary carcinoma of the urethra in the pendulous urethra may receive a distal urethrectomy. Alternatively, a partial penectomy can

be considered. A total penectomy may be necessary in cases of recurrence.

• Female patients

with T2 primary carcinoma of the urethra may be treated with urethrectomy and cystectomy with organ-sparing approaches when feasible

in appropriately selected cases.

Pelvic Exenteration (category 2B)

• Therapy for recurrence in female patients with ≥T2 primary carcinoma of the urethra.

• Ilioinguinal lymphadenectomy and/or chemoradiotherapy can be considered in patients with ≥T3 disease.

Continued PRINCIPLES OF SURGICAL MANAGEMENT

NCCN recommendations have been developed to be inclusive of individuals of all sexual and gender identities to the greatest extent possible. On this page, the terms male and female refer to sex assigned at birth.

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-B 4 OF 4

Endoscopic Management of Upper Tract Urothelial Cancer (UTUC)

• Favorable clinical and pathologic criteria for nephron preservation:

Low-grade tumor based on cytology and biopsy

Papillary architecture

Tumor size <1.5 cm

Unifocal tumor

Cross-sectional imaging showing no concern for invasive disease

• For favorable tumors - ureteroscopic and percutaneous management provide similar survival outcomes compared to nephroureterectomy

• Less favorable clinical and pathologic criteria for nephron preservation:

Multifocal tumors

Flat or sessile tumor architecture

Tumor size >1.5 cm

High-grade tumors

cT2–T4 tumors

Mid and proximal ureteral tumor due to technical challenges

Tumor crossing infundibulum or ureteropelvic junction

• Imperative indications for conservative therapy of UTUC

Bilateral renal pelvis and/or urothelial carcinoma of the ureter

Solitary or solitary functioning kidney

Chronic kidney disease/renal insufficiency

• Percutaneous or ureteroscopic surgical procedures

Tumor fulguration/cautery

Tumor resection incorporating electrical energy, baskets, or cold cup devices with fulguration of the tumor bed

Laser therapies Extirpative surgical procedures

Segmental ureterectomy ± ureteral reimplantation for distal ureteral tumors

Complete ureterectomy with ileal ureter replacement (proximal/mid-ureteral tumors)

• Topical immunotherapy and chemotherapy management (see Principles of Instillation Therapy [BL-F 3 of 4] for more information).Patients

with renal pelvis and urothelial carcinoma of the ureter managed with nephron-preserving procedures and adjunctive therapies require

long-term surveillance, including cross-sectional urography or endoscopic visualization. Treatment can be associated with patient anxiety,tumor seeding, and the need for multiple procedures and ultimate nephroureterectomy with bladder cuff. Clinical/pathologic understaging is problematic. Recurrence or tumor persistence might be life-threatening due to disease progression.

PRINCIPLES OF SURGICAL MANAGEMENT

NCCN Guidelines Index Table of Contents Discussion

National Comprehensive Cancer Network®

PRINCIPLES OF PATHOLOGY MANAGEMENT

2022 WHO Classification of Tumors of the Urothelial Tract1,2

Urothelial Tumors

Mesenchymal Tumors

●Invasive urothelial carcinoma subtypes

Squamous Cell Neoplasms

●Rhabdomyosarcoma

Conventional urothelial carcinoma

●Pure squamous cell carcinoma

●Leiomyosarcoma

Infiltrating urothelial carcinoma with squamous differentiation

●Verrucous carcinoma

●Angiosarcoma

●Squamous cell papilloma

●Malignant inflammatory myofibroblastic tumor

Infiltrating urothelial carcinoma with glandular differentiation

Glandular Neoplasms

●Malignant perivascular epithelioid cell tumor

Infiltrating urothelial carcinoma with trophoblastic differentiation

●Adenocarcinoma,NOS

● Malignant solitary fibrous tumor

Mucinous

Mixed

●Villous adenoma

Urothelial Tract Hematopoietic and Lymphoid Tumors

Miscellaneous Tumors

Micropapillary urothelial carcinoma

Lymphoepethielioma-like urothelial carcinoma

Urachal Carcinoma

●Epithelial tumors of the upper urinary tract

Plasmacytoid urothelial carcinoma

Tumors of Müllerian Type

●Tumors arising in a bladder diverticulum

Sarcomatoid urothelial carcinoma

●Clear cell carcinoma

●Malignant melanoma

Giant cell urothelial carcinoma

●Endometrioid carcinoma

●Carcinoma of Skene,Cowper,and Littre glands

Lipid-rich urothelial carcinoma

Neuroendocrine Tumors

Clear cell (glycogen rich) urothelial carcinoma

●Small cell neuroendocrine carcinoma

●Metastatic tumors and tumors extending from other organs

Poorly differentiated urothelial carcinoma

●Large cell neuroendocrine carcinoma

●Noninvasive urothelial neoplasms Urothelial CIS

●Well-differentiated neuroendocrine tumor

●Paraganglioma

Noninvasive papillary urothelial carcinoma, low grade

1Moch H,Amin MB,Berney DM,et al.The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs- Part A: Renal, Penile, and Testicular Tumours.Eur Urol 2022;82;458-468.

aThe term “urothelial dysplasia” is very rarely used. Its morphologic features are poorly defined and interobserver reproducibility of this diagnosis is very low.

Note: All recommendations are category 2A unless otherwise indicated.

Continued

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PRINCIPLES OF PATHOLOGY MANAGEMENT

Note: All recommendations are category 2A unless otherwise indicated.

BL-C 2 OF 2

3 CAP Cancer Protocol Templates (https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates).4 Cheng L, et al. Non-invasive papillary urothelial carcinoma, high-grade. In: WHO Classification of Tumors. 5th: Urinary and Male Genital Tumors. WHO Classification of Tumors Editorial Board; International Agency for Research on Cancer; 2022:143-146.

5 Bochner BH, et al. Urinary Bladder. In: Amin MB, ed. AJCC Cancer Staging Manual. 8th Springer; 2017:757-765.

• The pathology report on biopsy/TURBT specimens should:

Include items listed in the College of American Pathologists (CAP) Cancer Protocol for reporting results (tumor site, histologic subtype,

histologic grade, tumor extent, and lymphovascular invasion if present)3

Example:

◊ Urinary bladder, tumor, TUR:

– High-grade urothelial carcinoma

▪ Carcinoma infiltrates lamina propria

▪ Muscularis propria present with invasion by tumor

▪ Lymphovascular space invasion present

▪ pT2

For tumors with intratumoral grade heterogeneity: tumors should be classified as high grade if the high-grade component represents

>5% of the tumor. If the high-grade component is <5%, the tumor should be classified descriptively as “low grade with <5% high-grade

component” as these may have a prognosis that is closer to low-grade tumors.4

Detail if muscularis propria (detrusor muscle) is present or absent (in addition to describing if invasion is present as per the reporting

protocol).

Describe if adjacent urothelial CIS is present.

Urothelial carcinomas with an inverted growth pattern should be graded similar to the system for papillary tumors as described above.

Mixed neuroendocrine carcinoma of the bladder should specify the type(s) and percentage of the neuroendocrine component(s) present.

In addition to presence or absence of lamina propria invasion, the report should attempt to describe the extent of lamina propria invasion

as early invasion/microinvasion or more extensive invasion. The exact method for characterizing early invasion versus more extensive

invasion of lamina propria has not been defined/optimized; however, any of the following methods could be used as detailed in the 8th

edition of the AJCC Cancer Staging Manual.5

◊ <1 high power field or greatest invasive tumor diameter of ≤1 mm or invasive tumor above muscularis mucosae extending to a depth of≤2 mm

• The pathology report on cystectomy specimens should:

Include items listed in the CAP Cancer Protocol for reporting results.3

• Consultation/re-review from an experienced genitourinary (GU) pathologist should be obtained as required for confirming clinically

significant rare subtype histology, confirming metastatic carcinoma of urothelial origin, and in clinically discrepant scenarios.

NCCN Guidelines Index Table of Contents Discussion

National NCCN Comprehensive NCCN Guidelines Version 2.2025 Bladder Cancer

BLADDER CANCER: NON-UROTHELIAL AND UROTHELIAL WITH SUBTYPE HISTOLOGY

Mixed Histology:

combination chemotherapy with paclitaxel, ifosfamide, and cisplatin may be considered.7

●Urothelial carcinoma plus squamous differentiation or adenocarcinoma differentiation should be identified because of the potential to have a more aggressive natural history.

●Consider postoperative RT in selected cases(positive margins).8

●These are usually treated in a similar manner to pure urothelial carcinoma of the bladder.

Pure Adenocarcinoma Including Urachal Carcinoma:

●There is no proven role for neoadjuvant/advjuvant chemotherapy for pure adenocarcinomas of the bladder, including urachal carcinoma.

Aggressive Subtype Histologies:

●Micropapillary,1,2 plasmacytoid,3 small cell/neuroendocrine, and sarcomatoid histologies(in pure or mixed form with associated urothelial carcinoma) are generally at higher risk for progression to muscle-invasive disease and a more aggressive approach should be considered.

●Local control with surgery or RT and best supportive care are recommended. See NCCN Guidelines for Palliative Care.

●For urachal carcinoma with localized disease, a partial or complete cystectomy with en bloc resection of the urachal ligament with umbilicus and lymph node dissection is recommended.

Pure Small Cell Carcinoma or Mixed Histology with Any Small Cell Component(or neuroendocrine features):

●Neurologic/brain imaging is recommended (BL-A 3 of 5).

●Concurrent chemoradiotherapy or neoadjuvant systemic therapy followed by local treatment(cystectomy or RT) is recommended for any patient with small cell component histology with localized disease regardless of stage(including non-muscle-invasive disease).

●Consider metastatic chemotherapy regimens seen in the NCCN Guidelines for Colon Cancer).

●For node-positive disease, consider regimens recommended for advanced or metastatic disease in the NCCN Guidelines for Colon Cancer or GemFLP[5-FU, leucovorin, gemcitabine, and cisplatin]). Consider post-chemotherapy surgical consolidation in responding disease.

●Neoadjuvant systemic therapy

Regimens recommended in the NCCN Guidelines for Small Cell Lung Cancer-Principles of Sytemic Therapy or

●For advanced disease, clinical trial is preferred. For selected patients, regimens recommended for advanced or metastatic disease in the NCCN Guidelines for Colon Cancer, regimens for metastatic injury, ifosfamide, and cisplatin), are options.

Alternating ifosfamide+ doxorubicin with etoposide+ cisplatin4-6

●Metastatic systemic therapy

●For non-urachal pure adenocarcinoma, consider additional metastatic workup. See NCCN Guidelines for Occult Primary.

Regimens recommended in the NCCN Guidelines for Small Cell Lung Cancer-Principles of Systemic Therapy or

Alternating ifosfamide+ doxorubicin with etoposide+ cisplatin4-6

Primary Bladder Sarcoma:

Pure Squamous Carcinoma:

●Treatment as per NCCN Guidelines for Soft Tissue Sarcoma.

●There is no proven role for neoadjuvant/adjuvant chemotherapy for pure squamous cell carcinoma of the bladder.

●Local control with surgery or chemoradiotherapy and best supportive care(NCCN Guidelines for Palliative Care) are recommended.

●For advanced disease, clinical trial is preferred. For selected patients,

Note: All recommendations are category 2A unless otherwise indicated. NCCN Guidelines Index Table of Contents Discussion 2 OF 2 BLADDER CANCER: NON-UROTHELIAL AND UROTHELIAL WITH SUBTYPE HISTOLOGY

References

NCCN Guidelines Index Table of Contents Discussion

National Comprehensive Cancer Cancer Network®

FOLLOW-UP

No single follow-up plan is appropriate for all patients. The follow-up tables are to provide guidance, and should be modified for the individual patient based on sites of disease, biology of disease, and length of time on treatment. Reassessment of disease activity should be performed in patients with new or worsening signs or symptoms of disease, regardless of the time interval from previous studies. Further study is required to define optimal follow-up duration.

Table 1: AUA Risk Stratification for Non-Muscle-Invasive Bladder Cancer*

|Low Risk|Intermediate risk|High Risk| |---|---|---| |● Papillary urothelial neoplasm of low malignant potential ● Low-grade urothelial carcinoma|● Low-grade urothelial carcinoma|● High-grade urothelial carcinoma| |● Paad 10 and|>3 cm or|T1 or| |● Ta and|Multifocal or|>3 cm or| |● ≤3cm and|Recurrence within 1 year|Multifocal| |● Solitary|● High-grade urothelial carcinoma|● Very-high-risk features(any): BCG unresponsivea| ||Ta and|BCG unresponsivea Certain histopathologic subtypesb| ||Solitary|Lymphosvascular invasion|

Adapted with permission from Chang SS, Boorjian SA, Chou R,et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016;196:1021-1029.

*Within each of these risk strata an individual patient may have more or less concerning features that can influence care.

Table 2: Low-Risk,6 Non-Muscle-Invasive Bladder Cancer

|Test|Year|Year|Year|Year|Year|| |---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10| |Cystoscopy|3,12|Annually|Annually|Annually|Annually|Annually| |Upper tract and abdomen/pelvis imaging|Baseline imaging|As clinically indicated||||| |Blood tests|N/A|N/A|N/A|N/A|N/A|N/A| |Urine tests|N/A|N/A|N/A|N/A|N/A|N/A| |Intermediate Risk,Non-Muscle Invasive (BL-E 2 of 6)|Post-Bladder Sparing (BL-E 5 of 6)|||||| |High-Risk,Non-Muscle Invasive (BL-E 2 of 6)|Metastatic Disease: Surveillance (BL-E 6 of 6)|||||| |Post-Cystectomy Non-Muscle-Invasive Bladder Cancer (BL-E 3 of 6)|Recurrent or Persistent Disease (BL-11)||||||

Intermediate Risk, Non-Muscle Invasive (BL-E 2 of 6)High-Risk, Non-Muscle Invasive (BL-E 2 of 6)

Post-Bladder Sparing (BL-E 5 of 6)Metastatic Disease: Surveillance (BL-E 6 of 6)Recurrent or Persistent Disease (BL-11)

Post-Cystectomy Non-Muscle-Invasive Bladder Cancer (BL-E 3 of 6)Post-Cystectomy Muscle-Invasive Bladder Cancer (BL-E 4 of 6)

a Kamat AM, et al. J Clin Oncol 2016;34:1935-1944.

b See aggressive subtype histologies listed on Bladder Cancer: Non-Urothelial and Urothelial with Subtype Histology(BL-D).

See NCCN Guidelines for Survivorship

c See AUA Risk Stratification for Non-Muscle-Invasive Bladder Cancer definitions on BL-2.

d Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

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Table 3: Intermediate Risk,c Non-Muscle-Invasive Bladder Cancer

|Test|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10| |Cystoscopy|3,6,12|Every 6 mo|Annually|Annually|As clinically indicated|| |Upper tract and abdomen/pelvis imagingd|Baseline imaging|As clinically indicated||||| |Blood tests|N/A|N/A|N/A|N/A|N/A|N/A| |Urine tests|Urine cytology 3,6,12|Urine cytology every 6 mo|Annually|Annually|As clinically indicated||

Table 4: High-Risk, ${ }^{C}$ Non-Muscle-Invasive Bladder Cancer

|Test|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10| |Cystoscopy|Every 3 mo|Every 3 mo|Every 6 mo|Every 6 mo|Annually|As clinically indicated| |Upper tract imagingd|Baseline imaging, and at 12 mo|Every 1-2 y|Every 1-2 y|Every 1-2 y|Every 1-2 y|As clinically indicated| |Abdomen/pelvis imagingd|Baseline imaging|As clinically indicated||||| |Blood tests|N/A|N/A|N/A|N/A|N/A|N/A| |Urine tests|●Urine cytology every 3 mo ●Consider urinary urothelial tumor markers (category 2B)|Urine cytology every 6 mo|Annually||||

C See AUA Risk Stratification for Non-Muscle-Invasive Bladder Cancer definitions on BL-2.

d Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

Note: All recommendations are category 2A unless otherwise indicated.

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FOLLOW-UP

Table 5: Post-Cystectomy Non-Muscle-Invasive Bladder Cancer

|Test|Year|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10|>10| |Cystoscopy|N/A|N/A|N/A|N/A|N/A|N/A|N/A| |Imagingd|·CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) annually|CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) annually|Renal US annuallye|As clinically indicated|||| |Blood tests|·Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFT every 3-6 mo ●CBC,CMP every 3-6 mo if received chemotherapy|●Renal function testing (electrolytes and creatinine) annually ●LFTf annually ●B12 annually based on clinical judgment|B12 annually based on clinical judgment||||| |Urine tests|·Consider urine cytology every 6-12 mo ●Consider urethral wash cytology every 6-12 mo9|Urine cytology as clinically indicated Urethral wash cytology as clinically indicated||||||

Post-Cystectomy MIBC(BL-E 4 of 6)

Post-Bladder Sparing(BL-E 5 of 6)

Recurrent or Persistent Disease(BL-11)

d Principles of Imaging for Bladder/Urothelial Cancer(BL-A).

e Renal US to look for hydronephrosis.

f Liver function testing(LFT) includes aspartate aminotransferase(AST), alanine aminotransferase(ALT), bilirubin,and alkaline phosphatase.

9 Urethral wash cytology is reserved for patients with high-risk disease. High-risk disease includes: positive urethral margin, multifocal CIS, and prostatic urethral invasion.

See NCCN Guidelines for Survivorship

Note: All recommendations are category 2A unless otherwise indicated.

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Table 6: Post-Cystectomy Muscle-Invasive Bladder Cancer

|Test|Year|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10|>10| |Cystoscopy|N/A|N/A|N/A|N/A|N/A|N/A|N/A| |Imagingd|●CTU or MRU (image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo ●CT chest (preferred) or chest x-ray annually or every 3-6 mo ●FDG-PET/CT (category 2B) only if metastatic disease suspected|●Abdomen/pelvis CT or MRI annually ●CT chest (preferred) or chest x-ray annually or ●FDG-PET/CT (category 2B) only if metastatic disease suspected|Renal US annually e|As clinically indicated|||| |Blood tests|●Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFTf every 3-6 mo ●BCT2 every 3-6 mo 3-6 mo if received chemotherapy|●Renal function testing (electrolytes and creatinine) annually ●LFTf annually by 12 annually based on clinical judgment|Renal US annually e|As clinically indicated|||| |Urine tests|●Consider urine cytology every 6-12 mo ●Consider urethral wash cytology every 6-12 mo9|Urine cytology as clinically indicated Urethral wash cytology as clinically indicated||||||

Post-Bladder Sparing(BL-E 5 of 6)

Recurrent or Persistent Disease(BL-11)

d Principles of Imaging for Bladder/Urothelial Cancer(BL-A).

e Renal US to look for hydronephrosis.

fLFT includes AST,ALT,bilirubin,and alkaline phosphatase.

9 Urethral wash cytology is reserved for patients with high-risk disease. High-risk disease includes: positive urethral margin, multifocal CIS, and prostatic urethral invasion.

See NCCN Guidelines for Survivorship

NCCN

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FOLLOW-UP

Table 7: Post-Bladder Sparing (ie, Partial Cystectomy or Chemoradiation"h)

|Test|Year|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10|>10| |Cystoscopy|Every 3 mo|Every 3 mo|Every 6 mo|Every 6 mo|Annually|Annually|As clinically indicated| |lmagingd|●CTU or MRU (image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo for MIBC ●CT chest (preferred) or chest x-ray every 3-6 mo for MIBC ●FDG-PET/CT (category 2B) only if metastatic disease suspected|●Abdomen/pelvis CT or MRI annually ●CT chest (preferred) or chest x-ray annually or ●FDG-PET/CT (category 2B) only if metastatic disease suspected|As clinically indicated||||| |Blood tests|·Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFT f every 3-6 mo ●CBC.MMP every 3-6 mo if received chemotherapy|●Renal function testing (electrolytes and creatinine) as clinically indicated|||||| ||||||||| |Urine tests|Urine cytology every 6-12 mo|Urine cytology as clinically indicated||||||

d Principles of Imaging for Bladder/Urothelial Cancer(BL-A).

f LFT includes AST, ALT, bilirubin, and alkaline phosphatase.

h For patients who are not eligible for aggressive therapy, less frequent surveillance may be warranted(eg, cystoscopy every 6 months, extended to annually over time).i PET/CT not recommended for NMIBC.

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FOLLOW-UP

Table 8: Metastatic Disease: Surveillance

|Test|Year|Year|Year|Year|Year|Year|Year|Year| |---|---|---|---|---|---|---|---|---| |Test|1|2|3|4|5|5-10|>10|| |Cystoscopy|●As clinically indicated|||||||| |Imagingd|●CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo if clinically indicated and with any clinical change or new symptoms ●CT chest/abdomen/pelvis every 3-6 mo and with any clinical change or new symptoms or ●FDG-PET/CT(category 2B)|||||||| |Blood tests|●CBC,CMP every 1-3 mo ●B12 annually for patients who had undergone a cystectomy based on clinical judgment|||||||| |Urine tests|●Urine cytology as clinically indicated||||||||

d Principles of Imaging for Bladder/Urothelial Cancer(BL-A).

Note: All recommendations are category 2A unless otherwise indicated.

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PRINCIPLES OF INSTILLATION THERAPY

Indications: Based on probability of recurrence and progression to muscle-invasive disease, such as size, number, and grade.

Intravesical Therapy for Bladder Cancer

Immediate Postoperative Intravesical Chemotherapy

• Clinical Presentation and Initial Evaluation (BL-1)

• A single instillation of chemotherapy is administered within 24 hours of surgery (ideally within 6 hours).

• Gemcitabine (category 1) (preferred)1 and mitomycin (category 1)2 are the most commonly used agents in the United States for intravesical chemotherapy. Thiotepa does not appear to be effective.3

• Immediate postoperative intravesical chemotherapy reduces the 5-year recurrence rate by approximately 35% and has a number needed to

treat to prevent a recurrence of 7. However, it does not reduce the risk of progression or the risk of cancer mortality.3

• It is not effective in patients with an elevated EORTC recurrence risk score (≥5). This includes patients with ≥8 tumors and those with

≥1 recurrence per year.

• Most efficacious in patients with low-grade, low-volume Ta urothelial cancer.

• Contraindications include: bladder perforation, known drug allergy.

Induction (Adjuvant) Intravesical Chemotherapy or BCG

• Treatment option for NMIBC.

• The most commonly used agents are BCG, mitomycin, and gemcitabine.

• Initiated 3–4 weeks after TURBT with or without maintenance.

• Weekly instillations during induction are given for approximately 6 weeks.

• Maximum of 2 consecutive cycle inductions without complete response.

• Withhold if traumatic catheterization, bacteriuria, persistent gross hematuria, persistent severe local symptoms, or systemic symptoms.

Maintenance Intravesical BCG

• Although there is no standard regimen for maintenance BCG, many NCCN Member Institutions follow the SWOG regimen consisting of a

6-week induction course of BCG followed by maintenance with 3 weekly instillations at months 3, 6, 12, 18, 24, 30, and 36.4

• Ideally maintenance should be given for 1 year for intermediate-risk and 3 years for high-risk NMIBC.

• BCG would be withheld if traumatic catheterization, bacteriuria, persistent gross hematuria, persistent severe local symptoms, or systemic

symptoms.

• Dose reduction is encouraged if there are substantial local symptoms during maintenance therapy.

• Data suggest the benefit of maintenance BCG therapy through a decreased rate of recurrence for NMIBC.4

Continued References

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BL-F 2 OF 4 References

Intravesical BCG Principles During Time of BCG Shortage:

• BCG induction and maintenance should be prioritized for patients at high risk for recurrence (eg, high-grade T1 and CIS), especially in the

early maintenance period (ie, 3 and 6 months post-induction).

• BCG maintenance for patients with intermediate-risk NMIBC can be risk adapted to prioritize patients with high-risk NMIBC.

• BCG maintenance for patients with high-risk NMIBC should be stopped at 1 year.

• Consider induction with alternative agents if BCG is completely not available.

Alternative options include: sequential gemcitabine/docetaxel, mitomycin, gemcitabine, epirubicin, valrubicin, docetaxel, or sequential

gemcitabine/mitomycin.

• Consider a clinical trial if available.

• If feasible, the dose of BCG may be split (1/3 or 1/2 dose) so that multiple patients may be treated with a single vial (for induction or highpriority maintenance therapy).

Continued PRINCIPLES OF INSTILLATION THERAPY

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BL-F 3 OF 4

Indications: Based on probability of recurrence and progression to muscle-invasive disease, such as size, number, and grade.

Topical or Percutaneous Administration of Chemotherapy or BCG• Although the target site differs, the principles of this treatment are similar to intravesical therapy. Topical chemotherapeutic agents aredelivered by instillation. Administration can be percutaneous or through a retrograde approach using a catheter. There is no standardregimen and patients should be referred to an institution with experience in this treatment or a clinical trial.• Topical immunotherapy and chemotherapy management

BCG, mitomycin

Route of administration might include percutaneous antegrade (preferred) or retrograde ureteral catheters.

Induction and maintenance therapy regimens, similar to intravesical therapy, can be used.

Postsurgical Intraprostatic BCG for Urothelial Carcinoma of the Prostate• Treatment for patients with ductal + acini, or prostatic urethra involvement. See Urothelial Carcinoma of the Prostate (UCP-1).• Induction (adjuvant) therapy should be initiated 3–4 weeks after TURP.• Induction BCG should be followed with maintenance BCG.• Data indicate a reduction in recurrence in the prostate in patients with superficial disease.5-11

Postsurgical Intraurethral Therapy for Primary Carcinoma of the Urethra• Consider as primary treatment for select patients with CIS, Ta, or T1 disease. See Primary Carcinoma of the Urethra (PCU-2).• Induction (adjuvant) therapy should be initiated 3–4 weeks after TUR.• The most commonly used agents are BCG, mitomycin, and gemcitabine.• Role of maintenance in this context is uncertain.• Efficacy of this treatment in primary carcinoma of the urethra has not been established.

Intrapelvic and Intravesical Therapy for Upper Tract Tumors• Primary Therapy

Complete or near complete endoscopic resection or ablation is recommended prior to mitomycin ureteral gel application, which is mostsuitably indicated for a residual, low-grade, low-volume (5–15 mm), solitary tumor in the upper urinary tract for a patient who is not a candidate for or not seeking nephroureterectomy as a definitive treatment. Mitomycin for pyelocaliceal application may be administered via ureteral catheter or a nephrostomy tube.• Postsurgical Therapy Consider intrapelvic therapy for patients with non-metastatic, low-grade tumors of the renal pelvis. See Upper GU Tract Tumors: RenalPelvis (UTT-1).◊ Intrapelvic induction (adjuvant) therapy should be initiated 3–4 weeks after endoscopic resection.◊ The most commonly used agents for intrapelvic therapy are BCG, mitomycin C, and gemcitabine.◊ Role of maintenance following intrapelvic therapy in this context is uncertain.◊ Efficacy of intrapelvic therapy in upper urinary tract cancer has not been established.12-14 Perioperative intravesical chemotherapy should be strongly considered following nephroureterectomy with cuff of bladder resection asrandomized trials have shown a decrease in intravesical recurrence.15-18 References PRINCIPLES OF INSTILLATION THERAPY

Note: All recommendations are category 2A unless otherwise indicated. NCCN Guidelines Index Table of Contents Discussion BL-F 4 OF 4

References

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National Comprehensive Cancer Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY

Neoadjuvant Chemotherapy(preferred for bladder)

Preferred regimen

●DDMVAC(dose-dense methotrexate,vinblastine,doxorubicin,and cisplatin) with growth factor support for 3-6 cycles1,2

Useful in certain circumstances

●Gemcitabine and cisplatin for 4 cycles3,4

|Adjuvant Therapy|Adjuvant Therapy| |---|---| |No previous platinum-based neoadjuvant therapy(pT3, pT4a, pN+)|Previous platinum-based neoadjuvant therapy(ypT2-ypT4a or ypN+)| |Preferred regimen|Other recommended regimen| |●DDMVAC with growth factor support for 3-6 cycles1,2|●Nivolumab6| |Other recommended regimens|●Pembrolizumab7| |●Nivolumab6|| |●Pembrolizumab7||

●For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative chemotherapy.

●Randomized trials and meta-analyses show a survival benefit for cisplatin-based neoadjuvant chemotherapy (3 or 4 cycles) for MIBC.1,8,9

●Meta-analysis suggests overall survival benefit with adjuvant cisplatin-based chemotherapy for pathologic T3, T4 or N+ disease at cystectomy, if it was not given as neoadjuvant.9

●Neoadjuvant chemotherapy is preferred over adjuvant-based chemotherapy on a higher level of evidence data.

●DDMVAC is preferred over standard MVAC based on category 1 evidence for metastatic disease showing DDMVAC to be better tolerated and more effective than conventional MVAC in advanced disease.2,10 Based on these data, the traditional dose and schedule for MVAC is no longer recommended.

●Perioperative gemcitabine and cisplatin is a reasonable alternative to DDMVAC based on category 1 evidence for metastatic disease showing equivalence to conventional MVAC in the setting of advanced disease.4,11

●For gemcitabine/cisplatin, a 21-day cycle is preferred. Better dose adherence may be achieved with fewer delays in dosing using the 21-day schedule.12

●Neoadjuvant chemotherapy is preferred for patients with UTUC, particularly for higher stage and/or grade tumors or concerning radiographic findings, as renal function will decline after nephroreterectomy and may preclude adjuvant therapy.

Multicenter data support the use of neoadjuvant, split-dose cisplatin-based chemotherapy(gemcitabine and cisplatin) for patients with high-grade UTUC.13 Staging for UTUC is less precise than for bladder cancer and understaging is common, necessitating discussion on the risk of under- versus over-treatment.

Adjuvant therapy should be considered if neoadjuvant therapy was not given for UTUC.14

●Carboplatin should not be substituted for cisplatin in the perioperative bladder cancer setting.

For patients with borderline renal function or minimal dysfunction, a split-dose administration of cisplatin may be considered(such as 35 mg/m2 on days 1 and 2 or days 1 and 8)(category 2B).While safer, the relative efficacy of the cisplatin-containing combination administered with such modifications remains undefined.

●For patients with borderline renal function, estimate GFR to assess eligibility for cisplatin. Consider timed urine collection, which may more accurately determine eligibility for cisplatin.

●Nivolumab and hyaluronidase-nvhy subcutaneous injection may be substituted for IV nivolumab. Nivolumab and hyaluronidase-nvhy has different dosing and administration instructions compared to IV nivolumab.

●Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV pembrolizumab. Pembrolizumab and berahyaluronidase alfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.

Note: All recommendations are category 2A unless otherwise indicated.

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Note: All recommendations are category 2A unless otherwise indicated.

BL-G 2 OF 7 References Continued

PRINCIPLES OF SYSTEMIC THERAPY

• Atezolizumab and hyaluronidase-tqjs subcutaneous injection may be substituted for IV atezolizumab. Atezolizumab and hyaluronidasetqjs has different dosing and administration instructions compared to atezolizumab for IV infusion.

• Nivolumab and hyaluronidase-nvhy subcutaneous injection may be substituted for IV nivolumab. Nivolumab and hyaluronidase-nvhy has different dosing and administration instructions compared to IV nivolumab.

• Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV pembrolizumab. Pembrolizumab and berahyaluronidase alfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.

First-Line Systemic Therapy for Locally Advanced or Metastatic Disease (Stage IV)

Preferred regimen

• Enfortumab vedotin-ejfv15,16 and pembrolizumab (category 1)

Other recommended regimens

• Gemcitabine and cisplatin4 (category

1) followed by avelumab maintenance therapy (category 1)a,17

• Gemcitabine, cisplatin, and nivolumab(category 1) followed by nivolumab

maintenance therapy18 (category 1)

• DDMVAC with growth factor support2,10(category 1) followed by avelumab

maintenance therapy (category 1)a,17

Useful in certain circumstances (cisplatin-ineligible)

• Gemcitabine and carboplatin19 followed by

avelumab maintenance therapy (category 1)a,17

• Pembrolizumab (for the treatment of patients

with locally advanced or metastatic urothelial

carcinoma who are not eligible for any platinumcontaining chemotherapy)20

• Atezolizumab21 (only for patients whose tumors

express PD-L1b or who are not eligible for any

platinum-containing chemotherapy regardless of PD-L1 expression) (category 2B)

a Maintenance therapy with avelumab only if there is no progression on first-line platinum-containing chemotherapy.b Atezolizumab: SP142 assay, PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area.

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National Comprehensive Cancer Network®

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PRINCIPLES OF SYSTEMIC THERAPY

|Second-Line Systemic Therapy for Locally Advanced or Metastatic Disease (Stage IV)||| |---|---|---| |Previous immunotherapy and entorumab vedotin-ejfv (no previous chemotherapy)||| |Preferred regimens|Other recommended regimens|Useful in certain circumstances| |●DDMVAC with growth factor support2|●Paclitaxel22 or docetaxel23|●Gemcitabine, cisplatin, and nivolumab (category 2B)| |●Gemcitabine and cisplatin4||| |●Gemcitabine and carboplatin (category 2B)||| |●Biomarker-directed therapy (see biomarker-directed therapy table, BL-G 4 of 7)||| |Previous chemotherapy (no previous immunotherapy or enfortumab vedotin-ejfv)${}^{c}$||| |Preferred regimens|Other recommended regimens|Useful in certain circumstances-| |●Pembrolizumab(category 1 post-platinum)25|●Paclitaxel22 or docetaxel23|●DDMVAC with growth factor support2| |●Enfortumab vedotin-ejfv and pembrolizumab ${}^{16}$|●Paclitaxel22 or docetaxel23|(category 2B)| |●Enfortumab vedotin-ejfv26||●Ifosfamide,doxorubicin,and gemcitabine30| |●Nivolumab27 (category 2B)||(category 2B)| |●Avelumab28,29 (category 2B)||●Gemcitabine and paclitaxel31 (category 2B)| |●Biomarker-directed therapy (see biomarker-directed therapy table,BL-G 4 of 7)||●Gemcitabine and cisplatin4 (category 2B)| |Previous immunotherapy (no previous chemotherapy or enfortumab vedotin-ejfv)||| |Preferred regimens|Other recommended regimens|Useful in certain circumstances| |●Enfortumab vedotin-ejfv and pembrolizumab|●Paclitaxel22 or docetaxel23|●Gemcitabine,cisplatin,and nivolumab (category 2B)| |●Gemcitabine and carboplatin||●fosfamide, doxorubicin,and gemcitabine30| |●Demcitabine and cisplatin4||| |●DDMVAC with growth factor support2||●fosfamide, doxorubicin,and gemcitabine30 (category 2B)| |●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)||| |Previous chemotherapy and immunotherapy (no previous enfortumab vedotin-ejfv)d,e||| |Preferred regimens|Other recommended regimens|Useful in certain circumstances| |●Enfortumab vedotin-ejfv32,33 (category 1)|●Enfortumab vedotin-ejfv and pembrolizumab|●Sacituzumab govitecan-hziy34| |●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)|●Paclitaxel22 or docetaxel23|| |●Gemcitabine and bisplatin 24||| |●DDMVAC with growth factor support2||| |●Enfortumab vedotin-ejfv32,23 (category 1)|●|| |●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)|●Paclitaxel22 or docetaxel23|●Sacituzumab govitecan-hziy34|

●Pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection may be substituted for IV nivolumab. Nivolumab and berahyaluronidase alfa-pmph has different dosing and administration instructions compared to IV pembrolizumab.

Note: All recommendations are category 2A unless otherwise indicated.

Footnotes

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National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

PRINCIPLES OF SYSTEMIC THERAPY

|Subsequent-Line Systemic Therapy for Locally Advanced or Metastatic Disease (Stage IV)d,e||| |---|---|---| |Previous chemotherapy,immunotherapy, and enfortumab vedotin-ejfv||| |Preferred regimen|Other recommended regimens|Useful in certain circumstances| |●Biomarker-directed therapy Biomarker-directed therapy (see biomarker-directed therapy table)|$\bullet$ Gemcitabine 24 ●Paclitaxel22 or docetaxel23 ●fosfamide, doxorubicin, and gemcitabine 30(category 2B). ● Gemcitabine and paclitaxel31 (category 2B)|$\bullet$ Sacituzumab govitecan-hzi ${}^{34}$|

Biomarker-Directed Therapy (regardless of previous therapy) (pan-cancer tumor-agnostic treatments can be considered for patients with actionable mutations)

●Erdafitinib (susceptible FGFR3 genetic alterations)f,35

●Fam-trastuzumab deruxtecan-nxki (HER2-positive, IHC 3+)^{36}

cIf progression-free survival>12 months after platinum (eg, cisplatin or carboplatin), consider re-treatment with platinum if the patient is still platinum eligible.

d Patient should have already received platinum and a checkpoint inhibitor, if eligible.

e These therapies are appropriate for patients who received a first-line platinum-containing chemotherapy followed by checkpoint inhibitor maintenance therapy or first-line therapy containing both platinum chemotherapy and an immune checkpoint inhibitor.

f Category 1 for patients who have already received platinum and a checkpoint inhibitor if eligible.

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National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

PRINCIPLES OF SYSTEMIC THERAPY

|Radiosensitizing Chemotherapy Regimens||| |---|---|---| |Preferred regimens · Cisplatinh alone37,38 ● Low-dose gemcitabine39-41 ● 5-FU and mitomycin42|Other recommended regimens · Cisplatin and 5-FU39,43 ● Cisplatin and paclitaxel39,44|Useful in certain circumstances (not generally used for curative-intent chemoradiotherapy for organ preservation) ●Taxane (docetaxel or paclitaxel) (category 2B) ●5-FU (category 2B) ●Capecitabine(category 3)|

gIn select cases these regimens may be used with palliative intent.

h Carboplatin is not an effective radiation sensitizer and should not be substituted for cisplatin with radiation(Rödel C, Grabenbauer GG, Kühn R, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002;20:3061-3071).

References

NCCN

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

PRINCIPLES OF SYSTEMIC THERAPY-REFERENCES

1Grossman HB, Natale RB, Tangen CM,et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.N Engl J Med 2003;349:859-866.

11 von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate,vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23:4602-4608.

2Sternberg CN, de Mulder PH, Schornagel JH, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin(MVAC)chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924, J Clin Oncol 2001;19:2638-2646.

12 Soto Parra H, Cavina R, Latteri F, et al. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol 2002;13:1080-1086.

13 Coleman J, Yip W, Wong N, et al. Multicenter phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for patients with high-grade upper tract urothelial carcinoma. J Clin Oncol 2023;41:1618-1625.

3Dash A, Pettus JA, Herr HW, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 2008;113:2471-2477.

14 Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma(the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet 2020;395:1268-1277.

4Von der Maase H, Hansen SW, Roberts JT,et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational multicenter, phase III study. J Clin Oncol 2000;18:3068-3077.

15 Powles T, Valderrama B, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 2024;390:875-888.

16 Hoimes C,Flaig T,Milowsky M,et al.Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. J Clin Oncol 2023;49:22-31.

5 Powles T, Catto JWF, Galsky MD, et al. Peroperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med 2024;391:1773-1786.

17 Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med 2020;383:1218-1230.

6Bajorin D,Witjes JA,Schwendj G,et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 2021;384:2102-2114.

18 van der Heijden MS, Sonpavde G, Powles T,et al. Nivolumab plus gemcitabine cisplatin in advanced urothelial carcinoma. N Engl J Med 2023;389:1778-1789.

7 Apolo AB, Ballman KV, Sonpavade G, et al. Adjuvant Pembrolizumab versus observation in Muscle-Invasive Urothelial carcinoma. N Engl J Med.2025;392(1):45-55

19 De Santis M, Bellmunt J, Mead G, et al. Randomized phase I/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy:EORTC study 30986.J Clin Oncol 2012;30:191-199.

8 Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: Update of a systematic review and meta-analysis of individual patient data advanced bladder cancer(ABC) meta-analysis collaboration. Eur Urol 2005;48:202-205; discussion 205-206.

20 Powles T, Csoszi T, Ozguroglu M,et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma(KEYNOTE-361):a randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:931-945.

21 Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017;389:67-76.

10 Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF

10 Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 2006;42:50-54.

22 Sideris S, Auon F, Zanaty M, et al. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer. Mol Clin Oncol 2016;4:1063-1067.

${}^{23}$ McCaffrey JA, Hilton S, Mazumdar M, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol 1997;15:1853-1857.

Note: All recommendations are category 2A unless otherwise indicated. NCCN Guidelines Index Table of Contents Discussion BL-G 7 OF 7 PRINCIPLES OF SYSTEMIC THERAPY -REFERENCES

References

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Note: All recommendations are category 2A unless otherwise indicated.

BL-H 1 OF 3

PRINCIPLES OF RADIATION MANAGEMENT OF INVASIVE DISEASE

Carcinoma of the Bladder: Unless otherwise stated, doses are 1.8–2.0 Gy daily fractionation.

• Precede RT alone or concurrent chemoradiotherapy by maximal TUR of the tumor when safely possible.

• Simulating and treating patients when they have an empty bladder is preferred for daily reproducibility (bladder full for tumor boosts is acceptable with

image guidance).

• Use multiple fields from high-energy linear accelerator beams.

• For invasive tumors, consider low-dose preoperative RT prior to segmental cystectomy (category 2B).

• Concurrent chemoradiotherapy or RT alone is most successful for patients without moderate/severe hydronephrosis and without extensive CIS associated with their muscle-invading tumor.

• For patients with stage Ta, T1, or CIS, external beam RT (EBRT) alone is rarely appropriate. For patients with recurrent Ta–T1 disease usually following

BCG therapy but without extensive CIS who are not candidates for cystectomy, concurrent chemoradiotherapy may be considered as a potentially curative alternative to radical cystectomy, which is the standard treatment by NCCN Guidelines.

• Treat the whole bladder with or without pelvic nodal RT 39.6–50.4 Gy using conventional or accelerated hyperfractionation. Elective treatment to the lymph nodes is optional and should take into account patient comorbidities and the risks of toxicity to adjacent critical structures. Then boost either the whole

or partial bladder between 60–66 Gy. For node-positive disease, consider boosting grossly involved nodes to the highest achievable dose that does not

violate dose-volume histogram (DVH) parameters based on the clinical scenario. Reasonable alternatives to conventional fractionation include taking the whole bladder to 55 Gy in 20 fractions, or using simultaneous integrated boosts to sites of gross disease.

• When irradiating the bladder only or bladder tumor boost, consider daily image guidance.

• Concurrent chemoradiotherapy is recommended for added tumor cytotoxicity, and can be given without significant increased toxicity over RT alone.

Concurrent 5-FU and mitomycin C or low-dose gemcitabine can be used instead of cisplatin-containing regimens in patients with low or moderate renal

function. Such therapy is optimally given by dedicated multidisciplinary teams.

• Concurrent chemoradiotherapy (preferred) or RT alone should be considered as potentially curative therapy for patients who are medically inoperable.

Concurrent chemoradiotherapy or RT alone should be considered for local palliation in patients with metastatic disease.

• When giving palliative radiation for metastatic bladder cancer or for recurrent pelvic tumor, combining radiation with radiosensitizing chemotherapy should be considered. See BL-G 5 of 7 for agents. Chemotherapy should not be used concurrently with high-dose (>3 Gy per fraction) palliative radiation.

• Treatment field should include whole bladder and all sites of gross disease plus or minus uninvolved regional lymph nodes. Regional lymph nodes include the hypogastric, obturator, internal and external iliac, perivesical, sacral, and presacral nodes. For involved nodal disease, the common iliac nodes are a

site of secondary involvement.

• For patients with pT3/pT4 pN0–2 urothelial (pure urothelial or primary urothelial mixed with other subtypes) bladder cancer following radical cystectomy

with ileal conduit, consider postoperative adjuvant pelvic RT (category 2B). Treatment field should encompass areas at risk for harboring residual

microscopic disease based on pathologic findings at resection and may include cystectomy bed and pelvic lymph nodes with doses in the range of 45 to

50.4 Gy. Involved resection margins and areas of extranodal extension could be boosted to 54–60 Gy if feasible based on normal tissue constraints.

• Conduct tumor status assessment after completion of full-dose primary chemoradiotherapy. See Table 7 on BL-E 5 of 6.

• In highly selected T4b tumor cases, may consider intraoperative RT.

• Concurrent chemoradiotherapy is generally most suitable for patients with solitary tumors, negative nodes, no extensive or multifocal CIS, no moderate/

severe tumor-related hydronephrosis, and good pre-treatment bladder function.

• For palliative RT, consider a dose of 30 Gy in 10 fractions or 21 Gy in 3 fractions.

• A meta-analysis of individual patient data from two randomized phase III studies (BC2001 and BCON) found that a hypofractionated schedule of 55 Gy in

20 fractions over 4 weeks is noninferior to the standard fractionation schedule of 64 Gy in 32 fractions over 6.5 weeks for both invasive local control and

toxicity and that the hypofractionated schedule is superior regarding invasive local control.

Continued References

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BL-H 2 OF 3

Carcinoma of the Urethra: Unless otherwise stated, doses are 1.8–2.0 Gy daily fractionation.

• Data support the use of RT for urothelial carcinoma and squamous cell carcinoma of the urethra (case series and experience treating these carcinomas arising from other disease sites); radiation can also be considered for adenocarcinomas of the urethra.

• Definitive Radiation Therapy (organ preservation)

cT2 cN0

◊ 66–70 Gy EBRT delivered to gross disease with a margin to encompass areas of potential microscopic spread. Concurrent chemotherapy with regimens used for bladder cancer is encouraged for added tumor cytotoxicity.

◊ Strongly consider prophylactic radiation treatment of regional-nodal basins (inguinal and low pelvic nodes for female and distal male tumors; pelvic lymph nodes for proximal male tumors).

cT3–T4, or lymph node positive

◊ 45–50.4 Gy EBRT delivered to gross disease with a margin to encompass areas of microscopic spread and to regional-nodal basins

(inguinal and low pelvic nodes for female and distal male tumors; pelvic lymph nodes for proximal male tumors). Boost gross primary

disease to 66–70 Gy and gross nodal disease to 54–66 Gy, if feasible. Dose delivered to gross nodal disease may be limited secondary to normal tissue dose constraints. Concurrent chemotherapy should be administered for added tumor cytotoxicity.

Postoperative adjuvant RT

◊ Treatment field should encompass areas at risk for harboring residual microscopic disease based on pathologic findings at resection and may include resection bed, inguinal lymph nodes, and pelvic lymph nodes. Areas at risk for harboring residual microscopic

disease should receive 45–50.4 Gy EBRT. Involved resection margins and areas of extranodal extension should be boosted to 54–60 Gy if feasible based on normal tissue constraints. Areas of gross residual disease should be boosted to 66–70 Gy, if feasible based on normal tissue constraints. Concurrent chemotherapy with regimens used for bladder cancer should be considered for added tumor cytotoxicity.

Recurrent disease

◊ Clinical target volume (CTV) should include gross disease in any suspected areas of spread at 66–74 Gy (higher dose up to 74 Gy for larger tumor and non-urothelial histology) and consideration can be given to elective regional-nodal basins (45–50.4 Gy) as discussed

above, if feasible based on normal tissue constraints.

PRINCIPLES OF RADIATION MANAGEMENT OF INVASIVE DISEASE

References

Note: All recommendations are category 2A unless otherwise indicated. NCCN Guidelines Index Table of Contents Discussion BL-H 3 OF 3

Abstract

Selective bladder preservation with twice-daily radiation plus 5-flourouracil/cisplatin (FCT) or daily radiation plus gemcitabine (GD) for patients with muscle invasive bladder cancer: Primary results of NRG/RTOG 0712-A randomized phase 2 multicenter trial [Abstract].

References

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

PRINCIPLES OF ALTERNATIVE RISK CLASSIFIERS AND BIOMARKERS

• A physician’s expertise and patient's preferences are critical when considering the diagnosis of bladder cancer, frequency of surveillance,

and treatment intensification or deintensification decisions. The NCCN Guidelines provide an evidence-based expert consensus that applies

to most patients, but cannot capture all the nuances of any individual patient case. The NCCN Bladder Cancer Panel acknowledges that

risk classifiers may provide additional prognostic information for estimating the risk of various outcomes after diagnosis or treatment.

These risk classifiers include, but are not limited to, staging systems derived from routinely available clinical information and nomograms,commercially available molecular tests, radiologic evaluations, and emerging artificial intelligence models. These risk classifiers should be

restricted to use in cases where there is concern that delivering guideline-directed practices or therapy may lead to over- or under-treatment or unacceptable toxicity.

Prognostic Biomarkers

• Since prognostic biomarkers are agnostic to the treatments received, evidence supporting their use may be derived from retrospective

studies, prospective registries, or prospective clinical trials. The NCCN Bladder Cancer Panel has elected not to list all the available and

emerging prognostic risk classifiers, regardless of the evidence level. The Panel encourages physicians and patients to carefully weigh

the quality and size of the studies that led to their development and validation when using them as clinical tools to aid in determining the

frequency of surveillance monitoring, treatment intensification, or deintensification decisions. To be clinically useful, the test should inform

the patient of the absolute risk of the event of interest (eg, metastasis or progression). Prognostic biomarkers may be used in considering

treatment intensification or deintensification decisions.

Predictive Biomarkers

• Predictive biomarkers inform decisions on whether specific interventions may be beneficial, futile, or harmful, regardless of the absolute

risk. To be classified as a predictive biomarker, a risk classifier must prove that a change in management alters the risk of an outcome of

interest. To do so, the risk classifier must be tested in data derived from prospectively randomized trials, where the randomization question was the management change, and the pre-specified endpoints of the trial were the outcome of interest.

Note: All recommendations are category 2A unless otherwise indicated.

BL-I 1 OF 3

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

Disease Contexts

• Germline Testing

The Panel recommends inquiring about the family and personal history of cancer and known germline variants at the time of initial

diagnosis. The criteria for germline testing should be reviewed at the time of the initial diagnosis and, if relevant, at recurrence.

• Non–Muscle-Invasive Bladder Cancer (NMIBC)

Biomarkers have a limited role in the initial evaluation and management of NMIBC. Any suspected patient with bladder cancer should

undergo cystoscopy, TURBT, and EUA for diagnosis/disease risk stratification, which will drive subsequent treatment options offered to

patients.

Office cystoscopy at recommended intervals is a critical diagnostic and surveillance tool for NMIBC. Omission or delay of cystoscopy is

acceptable only if a predictive biomarker has been tested and found to be non-inferior in a prospective randomized clinical trial.

Currently, there is no routine role for obtaining urine cytology or other urinary biomarkers in low-risk NMIBC.a

The ability of biomarkers to replace urine voided cytology, most notably in the surveillance of NMIBC (in the intermediate or greater risk

stratification groups), remains uncertain, and randomized clinical trials are required to conclusively address such questions.

The use of certain biomarkers can be considered in the evaluation and workup of gross hematuria, but this is outside the scope of this

guideline.

Biomarkers have the greatest clinical value in the further evaluation of patients with subjective findings at the time of office cystoscopy

(eg, focal or diffuse redness raising concern most notably in a patient with previous intravesical treatment that could explain such findings)

or in the context of abnormal voided cytology (most notably when the upper tract diagnostic imaging evaluation is negative). However, we

leave this to the discretion and clinical judgment of board-certified practicing urologists to determine if and when such biomarkers may be

clinically used in their practice.

• Muscle-Invasive Bladder Cancer (MIBC)/Resectable:

The Panel does not recommend routine somatic tumor testing unless it enables a patient to be considered for an available clinical trial.

The Panel recognizes that some ultrasensitive circulating tumor DNA (ctDNA) assays may have prognostic value after cystectomy.

However, to date, the Panel has concluded that there are insufficient data for ctDNA results to determine the course of surveillance or

therapy after complete surgical resection.

PRINCIPLES OF ALTERNATIVE RISK CLASSIFIERS AND BIOMARKERS

Note: All recommendations are category 2A unless otherwise indicated.

BL-I 2 OF 3

a See AUA Risk Stratification for Non–Muscle-Invasive Bladder Cancer definitions on BL-2.

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PRINCIPLES OF ALTERNATIVE RISK CLASSIFIERS AND BIOMARKERS

Disease Contexts (cont.)

• Locally Advanced Unresectable/Metastatic Bladder Cancer:

The Panel recommends somatic tumor testingb for all patients with unresectable or metastatic bladder cancer at the time of initial

diagnosis and, if relevant, at recurrence. Somatic tumor testing assays should cover FGFR3 alterations. A larger panel may be preferred to

identify rare mutations that may have approved therapies or allow for clinical trial eligibility.

The Panel recommends evaluation of microsatellite instability-high (MSI-H) and/or mismatch repair (MMR) status.

The Panel recommends immunohistochemistry (IHC) testing for HER2.

• Advanced Disease

Studies have demonstrated that ultrasensitive ctDNA assays may track the response to therapy and progression. However, there are

insufficient data that changes in therapy based on ctDNA significantly improve outcomes. Additionally, there are no data to date that ctDNA

clearance should be used to make decisions to alter or discontinue therapy.

Note: All recommendations are category 2A unless otherwise indicated.

BL-I 3 OF 3

b Molecular/genomic testing in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory, including FGFR RGQ reverse transcriptase polymerase chain reaction (RT-PCR) for FGFR3 genetic alterations and IHC for HER2 overexpression.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Upper GU Tract Tumors

NCCN Guidelines Index Table of Contents Discussion

![WORKUP\nPRIMARY TREATMENT^d\nEndoscopic resectione±postsurgical intrapelvic chemotherapy\nor or parenchymal in invasion\nNephrouterrectomy with perioperative intravesical chemotherapy\nAdjuvant Treatment and Discussion\nLow gradec\nRenal pelvis\nImaging of upper tract collecting systema· Cytology· Ureteroscopy and biopsy or percutaneous biopsy and/or selective washings\nNon-metastatic\nHigh grade,cl large,or parenchymal invasion\nNephrouterrectomy with perioperative intravesical chemotherapyf\nAn\nTreatment and Discussion\nAdjuvant Treatment and Contents Discussion\nRenal pelvis\nTREATMENT\nPRIMARY TREATMENT\n\nEndoscopic resectione±postsurgical intrapelvery chemotherapy of or parenchymal and chemotherapy of chemotherapy\nNephroureterectomy with cuff of bladder +regional lymphadenectomy ± perioperative intravesical chemotherapyf and cisplatin based neoadjuvant chemotherapy9in selected patients\nMetastatic\nSystemic therapyhym\nHigh grade,c large,or parenchymal invasion\nNephrouterrectomy with cuff of bladder output and general treatment. Mitomycin for pyelocaliceal application may be administered via ureteral catheter or a nephrostomy tube.\n4\n3\n4\n5\n6\n7\n8\n9\n6\n3\n4\n5\n6\nInstitute\mathttan\nararctivesd\npenual\nOpen $$\text{In aumary in Urothe7}\text{In}$$In aum.4\n3\n4\n5\n6\n4\n5\n6\n3\n4\n5\n6\nIn aum.4\n6\n3\n4\n5\n6\n4\n5\n6\n3\n4\n5\n6\nIn aum.5\nNCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal.\nEndometrial, and Gastric-Criteria for the Evaluation of Lynch Syndrome Based on Personal or Family History of Cancer.\nMontironi R, Lopez-Beltran A. The 2004 WHO classification of bladder tumors: A summary and commentary. Int J Surg Pathol 2005;13:143-153. See Principles of Pathology Management(BL-C).\nPrinciples of Sympal Management(BL-B).\ngPrinciples of Systemic Therapy(BL-G1 of 7\nPrinciples of Systemic Therapy(BL-G1 of 7\nPrinciples of Systemic Therapy(BL-G1 of 7\nPrinciples of Systemic Therapy(BL-G1 of 7\nThis systemic therapy's\nUnplature 2022, 10/10/25 @2025 National Comprehensive Cancer Network®(NCCN®),All rights reserved.NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.\n](2/aj0YEe4oUhYkBdfpda0fYP/figure92b41fb2d6ee47dc8512b3a6fa745035_0_4.png) a Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

bNCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal.Endometrial, and Gastric-Criteria for the Evaluation of Lynch Syndrome Based on Personal or Family History of Cancer.

cMontironi R, Lopez-Beltran A. The 2004 WHO classification of bladder tumors: A summary and commentary. Int J Surg Pathol 2005;13:143-153. See Principles of Pathology Management(BL-C).

dPrinciples of Surgical Management (BL-B).

`e Complete or near complete endoscopic resection or ablation is recommended prior to mitomycin ureteral gel application, which is most suitably indicated for a residual,low-grade, low-volume (5-15 mm), solitary tumor in the upper urinary tract for a patient who is not a candidate for or not seeking nephroutererectomy as a definitive treatment. Mitomycin for pyelocaliceal application may be administered via ureteral catheter or a nephrostomy tube.`

f Principles of Instillation Therapy(BL-F).

gPrinciples of Systemic Therapy (BL-G 1 of 7).

hSee Principles of Systemic Therapy (BL-G 2 of 7,3 of 7, and 4 of 7).

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Upper GU Tract Tumors

NCCN Guidelines Index Table of Contents Discussion

![WORKUP\nImaging of upper tract collecting system\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n×\n←\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n>-\n\n](2/aj0YEe4oUhYkBdfpda0fYP/figureacb5dff7504e452a83018b34a158258f_0_4.png) H See Principles of Systemic Therapy (BL-G 2 of 7, 3 of 7, and 4 of 7).

Metastatic→Systemic therapy

Note: All recommendations are category 2A unless otherwise indicated.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Upper GU Tract Tumors

NCCN Guidelines Index Table of Contents Discussion

PATHOLOGIC ADJUVANT TREATMENT STAGING

FOLLOW-UP

![\nAdjuvant treatment for renal pelvis and urothelial carcinoma of the ureter\npT0, pT1\npT0, pT3, pT4, pN+\n\nNon\nNone\nPTO, pT1\n\nIf no platinum neoadjuvant treatment given and pT3,pT4, or pN+\nAdjuvant platinum-based chemotherapy should be discussed9,j or 2B)\nConsider adjuvant nivolumab$g, j, k\ (Catérata\n4pT4, pN+\nR\n](2/aj0YEe4oUhYkBdfpda0fYP/figuree56ac6430037441cb819613cb75074c7_0_6.png) a Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

gPrinciples of Systemic Therapy(BL-G 1 of 7).

i The modifier "p" refers to pathologic staging based on surgical resection and lymph node dissection.

Follow recommendations for adjuvant chemotherapy after ensuring that patient is fully staged to rule out metastatic disease.

k Most appropriate for patients who value an opportunity to delay recurrence even if the chance of cure was not improved, and for whom the risk of side effects was acceptable.

Note: All recommendations are category 2A unless otherwise indicated.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Urothelial Carcinoma of the Prostate

NCCN Guidelines Index Table of Contents Discussion

WORKUP

PATHOLOGY

PATHOLOGY ADDITIONAL PRIMARY TREATMENTb

THERAPY FOR RECURRENCE

![Urothelial carcinoma of the prostate\ncarcinoma of the prostate\nDigital rectal examination (DRE)\n● Digital rectal examination (DRE)\nor prostate to include stroma\nstroma\nstroma\n● Prostate-specific antigen (PSA)\n● Needle biopsy if\n● Prostate at problems)\n● Needle biopsy if\n● Imaging of upper tract collecting system\n\n\nprostate at upper distance in the 2970s with 2000009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500\n](2/aj0YEe4oUhYkBdfpda0fYP/figuref3ff1e484574414981c11a0f963fb972_0_8.png) aPrinciples of Imaging for Bladder/Urothelial Cancer (BL-A).

bPrinciples of Surgical Management(BL-B).

cPrinciples of Systemic Therapy (BL-G 1 of 7).

d See Principles of Systemic Therapy (BL-G 2 of 7, 3 of 7, and 4 of 7).

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Primary Carcinoma of the Urethra

NCCN Guidelines Index Table of Contents Discussion

WORKUPa DIAGNOSIS

![Urothelial carcinoma of prostate UCP-1\n Urothelial carcinoma of prostate\nUCP-2\nPrimary carcinoma of non-prostatic male urethra or female urethra\n UCRAP\n DiAGNOSIS\n Susicion of carcinoma of the urethra\n Cystourethroscopy\n EUA\nTUR or transvaginal biopsy\nChest x-ray or CT\nMRI of pelvis with and without contrastb\nUrothelial Cancer of prostate of cST or or CTER\n SiC Ta, T1\n UCRAP\n CIS Ta, T1\n PCU-2\n\n T3, T4\n Palapable inguinal lymph nodes\n Distant metastasis\n PCU-3\n](2/aj0YEe4oUhYkBdfpda0fYP/figure003afaaf5eeb4ad0a9a48b3ddb6bbf83_0_5.png) aReferral to a specialized center is recommended.

bPrinciples of Imaging for Bladder/Urothelial Cancer (BL-A).

Note: All recommendations are category 2A unless otherwise indicated.

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Primary Carcinoma of the Urethra

NCCN Guidelines Index Table of Contents Discussion

CLINICAL ADDITIONAL PRIMARY $10$ ADJUVANT TREATMENT ${}^{C}$ ADJUVANT TREATMENT ${}^{N}$

CIS, Ta, T1 $\cdot$ $+$ Followed by intraurethral chemotherapy or BCG${}^{e}$ (selected cases)

![\nT2\nFemale\nFemale\n\nFemale\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n](2/aj0YEe4oUhYkBdfpda0fYP/figure4a3fe98c58494025a5a7414cd7009ac6_0_6.png) cPrinciples of Surgical Management(BL-B).

dIn patients with a prior radical cystectomy and a cutaneous diversion, consider a total urethrectomy.

e Principles of Instillation Therapy(BL-F).

f Consider neoadjuvant chemotherapy (category 2B) or chemoradiation.

9Principles of Systemic Therapy(BL-G 5 of 7).

hPrinciples of Radiation Management of Invasive Disease - Carcinoma of the Urethra(BL-H 2 of 3).

i Principles of Systemic Therapy (BL-G 1 of 7).

${}^{i}$ Chemotherapy regimen based on histology(Dayyani F, et al. Urol Oncol 2013;31:1171-1177). Also see Non-Urothelial Cell and Urothelial with Subtype Histology(BL-D).

${}^{k}$ Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

1Principles of Systemic Therapy (BL-G 2 of 7).

m See Principles of Systemic Therapy (BL-G 3 of 7 and 4 of 7).

${}^{n}$ Consider for local recurrence(± chemotherapy).

![National Comprehensive Currenta 构号\nNCCN 2025\nNCCN 2025\nNCCN 2025\nPrimary Carcinoma of the Urethra\nNCCN Guidelines Version 2.2025\nSUNCC\nCurrent 2025\nPrimary Carcinoma of the Urethra\n](2/aj0YEe4oUhYkBdfpda0fYP/figure34071d3040b44c96b54ab360a07d314e_0_1.png) NCCN Guidelines Index Table of Contents Discussion

![CLINICAL STAGING\nADDITIONAL WORKUP\nCNO\nT3, T4\nPalpable inguinal\nChest/abdomen/lympelis CT with contrast nodes\nCN2\nSurgery alone for non-urothelial histology\nPRIMARY TREATMENTC\nChemoradiotherapy9,h(preferred)±consolidative surgery\nor\nNeoadjuvant chemotherapy1,o (if urothelial carcinoma) and consolidation with surgery or RTH\nor\nRTHth\nSurgery alone for non-urothelial histology\nFollow-up→Recurrence→\nimaging\nHPLG\nRetourghk\n→ 依\nPelvic exenteration(category 2B)\n±ilioinguinal lymphadenectomy\nSurgery algorithm\n→ 依题意\nPelvicexenteration(category 2B)\nlymphadenectomy\nand/or\nChemoradiotherapy9,h\n→Systemic therapy J,l± sonidative surgery\nSystemic therapy j,l± sonidative surgery\nor\nNLP\nSurgery\nertual\ncRNA\nor\nMetastatic Disease (BL-10)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure3077a4bb74b042858162bec048ad6718_0_3.png) ![Distant metastasis\nMetastatic Disease(BL-10)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure890c1a6f7f1a401c857e72cf7fc29102_0_4.png) ${}^{c}$ Principles of Surgical Management(BL-B).

gPrinciples of Systemic Therapy(BL-G 5 of 7).

h Principles of Radiation Management of Invasive Disease- Carcinoma of the Urethra(BL-H 2 of 3).

i Principles of Systemic Therapy (BL-G 1 of 7).

Chemotherapy regimen based on histology(Dayyani F,et al. Urol Oncol 2013;31:1171-1177).Also see Non-Urothelial Cell and Urothelial with Subtype Histology(BL-D).

k Principles of Imaging for Bladder/Urothelial Cancer (BL-A).

${}^{1}$ Principles of Systemic Therapy (BL-G 2 of 7).

m See Principles of Systemic Therapy (BL-G 3 of 7 and 4 of 7).

°Data support neoadjuvant chemotherapy only for urothelial carcinoma.

Note: All recommendations are category 2A unless otherwise indicated.

NCCN Guidelines Index

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

Table 1. American Joint Committee on Cancer (AJCC)

TNM Staging System for Bladder Cancer 8th ed., 2017)

T Primary Tumor

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Ta Noninvasive papillary carcinoma

CIS Urothelial carcinoma in situ:“flat tumor”(Tis)

T1 Tumor invades lamina propria (subepithelial connective tissue)

T2 Tumor invades muscularis propria

pT2a Tumor invades superficial muscularis propria (inner half)

pT2b Tumor invades deep muscularisular propria (outer half)

T3 Tumor invades perivesical tissue

pT3a Microscopically

pT3b Macroscopically (extravesical mass)

T4 Extravesimal tumor directly invades any of the following:prostatic stroma, seminal vesicles,uterus, vagina, pelvic wall,abdominal wall

T4a Extravesimal tumor invades prostatic stroma, seminal vesicles,uterus, vagina

T4b Extravesimal tumor invades pelvic wall, abdominal wall

N Regional Lymph Nodes

NX Lymph nodes cannot be assessed

N0 No lymph node metastasis

N1 Single regional lymph node metastasis in the true pelvis(perivesical, obturator, internal and external iliac, or sacral lymph node)

N2 Multiple regional lymph node metastasis in the true pelvis(perivesical, obturator, internal and external iliac, or sacral lymph node metastasis)

N Regional Lymph Nodes

N3 Lymph node metastasis to the common iliac lymph nodes

M #Distant Metastasis

M0 No distant metastasis

M1 Distant metastasis

M1a Distant metastasis limited to lymph nodes beyond the common iliacs

M1b Non-lymph-node distant metastases

Histologic Grade(G)

For urothelial histologies, a low- and high-grade designation is used to match the current World Health Organization/International Society of Urological Pathology (WHO/ISUP) recommended grading system:

LG Low-grade

HG High-grade

For squamous cell carcinoma and adenocarcinoma, the following grading schema is recommended:

GX Grade cannot be assessed

G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

Table 2. AJCC Prognostic Groups

||T|N|M|T|T|N|M| |---|---|---|---|---|---|---|---| |Stage 0a|Ta|NO|M0||T1-T4a|N1|M0| |Stage 0is|CIS|NO|M0|Stage III|T1-T4a|N2,N3|M0| |(Tis)|||Stage IVA|T4b|Any N|M0|| |Stage I|T1|NO|M0||Any T|Any N|M1a| |Stage II|T2a|NO|M0|Stage IVB|Any T|Any N|M1b| ||T2b|NO|MO||||| |Stage IIIA|T3a|NO|MO||||| ||T3b|NO|MO||||| ||T4a|NO|MO|||||

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition(2017) published by Springer International Publishing.

NCCN Guidelines Index

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

Table 3. American Joint Committee on Cancer (AJCC)

TNM Staging System for Renal Pelvis and Ureter Cancer (8th ed., 2017)

T Primary Tumor

TX Primary tumor cannot be assessed

TO No evidence of primary tumor

Ta Papillary noninvasive carcinoma

CIS (Tis)

T1 Tumor invades subepithelial connective tissue

T2 Tumor invades the muscularis

T3 For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or the renal parenchyma.

For ureter only: Tumor invades beyond muscularis into periueric fat.

T4 Tumor invades adjacent organs, or through the kidney into the perinephric fat.

N Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed

NO No regional lymph node metastasis

N1 Metastasis ≤2 cm in greatest dimension, in a single lymph node

N2 Metastasis >2 cm in a single lymph node; or multiple lymph nodes

M Distant Metastasis

M0 No distant metastasis

M1 Distant metastasis

Histologic Grade(G)

For urothelial histologies, a low- and high-grade designation is used to match the current WHO/ISUP recommended grading system:

LG Low-grade

HG High-grade

For squamous cell carcinoma and adenocarcinoma, the following grading schema is recommended.

GX Grade cannot be assessed

G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

Table 4. AJCC Prognostic Groups

|T|N|M| |---|---|---| |Stage 0a|Ta|NO M| |Stage Ois|CIS|NO M| |(Tis)||(Tis)| |Stage I|T1|NO M| |Stage II|T2|NO M| |Stage III|T3|NO M| |Stage IV|T4|NX,NO M| |Any T|N1|M0| |Any T|N2|M0| |Any T|Any N|M1|

NCCN Guidelines Index

National Comprehensive Cancer Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

Table 5. American Joint Committee on Cancer (AJCC)

TNM Staging System for Urethral Carcinoma (8th ed.,2017)

Male Penile Urethra and Female Urethra

T Primary Tumor

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Ta Non-invasive papillary carcinoma

CIS (Tis)

T1 Tumor invades subepithelial connective tissue

T2 Tumor invades any of the following: corpus sponiosum, periurethral muscle

T3 Tumor invades any of the following: corpus cavernosum, anterior vagina

T4 Tumor invades other adjacent organs (e.g., invasion of the bladder wall)

Prostatic Urethra

T Primary Tumor

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Ta Non-invasive papillary carcinoma

CIS Carcinoma in situ involving the prostatic urethra or(Tis) perihurest or prostatic ducts without stromal invasion

T1 Tumor invades urethral subepithelial connective tissue immediately underlying the urothelium

T2 Tumor invades the prostatic stroma surrounding ducts either by direct extension from the urothelial surface or by invasion from prostatic ducts

T3 Tumor invades the periprostatic fat

T4 Tumor invades other adjacent organs(e.g.,extraprostatic invasion of the bladder wall, rectal wall)

N 2 Regional lymph Nodes

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Single regional lymph node metastasis in the inguinal region or true pelvis[periverical, obturator, internal(hypogastric) and external iliac], or presacral lymph node

N2 Multiple regional lymph node metastasis in the inguinal region or true pelvis[pervestical, obturator, internal(hypogastric) and external iliac], or presacral lymph node

M Distant Metastasis

M0 No distant metastasis

M1 Distant metastasis

Histologic Grade(G)

Grade is reported by the grade value. For urothelial histology, a low- and high-grade designation is used to match the current WHO/ISUP recommended grading system:

LG Low grade

HG High grade

For squamous cell carcinoma and adenocarcinoma, the following grading schema is recommended:

GX Grade cannot be assessed

G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual,

NCCN

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

ABBREVIATIONS

|ALT|alanine aminotransferase|MMR|mismatch repair| |---|---|---|---| |AST|aspartate aminotransferase|MRU|magnetic resonance| |BCG|Bacillus Calmette-Guérin||urography| |CAP|College of American Pathologists|NMIBC|microsatellite instability-high| |CBC|complete blood count||nMIBC| |CIS|carcinoma in situ|NOS|not otherwise specified| |CLIA|Clinical Laboratory|PA|posteroanterior| |Improvement Amendments|Improvement Amendments|PSA|prostate-specific antigen| |CMP|comprehensive panel|RT-PCR|reverse transcriptase polymerase chain reaction| |CNS|central nervous system|TUR|transurethral resection| |ctDNA|circulating tumor DNA|TUR|transurethral resection of bladder tumor| |CTU|computed tomography urography|TURP|transurethral resection of the prostate| |CTV|clinical target volume|UTUC|upper tract urothelial cancer| |DRH|dose-volume histogram||| |EBRT|external beam radiation therapy||| |EUA|examination under anesthesia||| |FDG|fluorodeoxyglucose||| |GFR|glomerular filtration rate||| |GU|genitourinary||| |H&P|history and physical||| |IHC|immunohistochemistry||| |IVP|intravenous pyelogram||| |LFT|liver function test||| |MIBC|muscle-invasive bladder cancer|||

|MMR|mismatch repair magnetic resonance urography| |---|---| |MSI-H|microsatellite instability-high| |NMIBC|non-muscle-invasive bladder cancer| |NOS|not otherwise specified| |PA|posteroanterior| |PSA|prostate-specific antigen| |RT-PCR|reverse transcriptase polymerase chain reaction| |TUR|transurethral resection| |TURBT|transurethral resection of bladder tumor| |TURP|transurethral resection of the prostate| |UTUC|upper tract urothelial cancer|

National Comprehensive Cancer Network®

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

|NCCN Categories of Evidence and Consensus|| |---|---| |Category 1|Based upon high-level evidence (≥1 randomized phase 3 trials or high-quality, robust meta-analyses), there is uniform NCCN consensus(≥85% support of the Panel) that the intervention is appropriate.| |Category 2A|Based upon lower-level evidence, there is uniform NCCN consensus(≥85% support of the Panel) that the intervention is appropriate.| |Category 2B|Based upon lower-level evidence, there is NCCN consensus(≥50%, but <85% support of the Panel) that the intervention is appropriate.| |Category 3|Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.|

All recommendations are category 2A unless otherwise indicated.

|NCCN Categories of Preference|| |---|---| |Preferred intervention|Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.| |Other recommended intervention|Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data; or significantly less affordable for similar outcomes.| |Useful in certain circumstances|Other interventions that may be used for selected patient populations (defined with recommendation).|

All recommendations are considered appropriate.

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Index Table of Contents Discussion

表 1
Low Risk	Intermediate Risk	High Risk
● Papillary urothelial neoplasm of low malignant potential ● Low grade urothelial carcinoma ● Ta and ●≤3cm and Solitary	● Low grade urothelial carcinoma ●T1 or >3 cm or Multifocal or Recurrence within 1 year ● High grade urothelial carcinoma ● Ta and ≤3cm and Solitary	● High grade urothelial carcinoma ● CIS or T1 or >3cm or Multifocal or Multifocal ● High grade urothelial carcinoma ● Very high risk features (any): BCG unresponsive = Certain histopathologic subtypes m Lymphovascular invasion -Prostatic urethral invasion

表 2
Low Risk	Intermediate risk	High Risk
● Papillary urothelial neoplasm of low malignant potential ● Low-grade urothelial carcinoma	● Low-grade urothelial carcinoma	● High-grade urothelial carcinoma
● Paad 10 and	>3 cm or	T1 or
● Ta and	Multifocal or	>3 cm or
● ≤3cm and	Recurrence within 1 year	Multifocal
● Solitary	● High-grade urothelial carcinoma	● Very-high-risk features(any): BCG unresponsivea
	Ta and	BCG unresponsivea Certain histopathologic subtypesb
	Solitary	Lymphosvascular invasion

表 3
Test	Year	Year	Year	Year	Year
Test	1	2	3	4	5	5-10
Cystoscopy	3,12	Annually	Annually	Annually	Annually	Annually
Upper tract and abdomen/pelvis imaging	Baseline imaging	As clinically indicated
Blood tests	N/A	N/A	N/A	N/A	N/A	N/A
Urine tests	N/A	N/A	N/A	N/A	N/A	N/A
Intermediate Risk,Non-Muscle Invasive (BL-E 2 of 6)	Post-Bladder Sparing (BL-E 5 of 6)
High-Risk,Non-Muscle Invasive (BL-E 2 of 6)	Metastatic Disease: Surveillance (BL-E 6 of 6)
Post-Cystectomy Non-Muscle-Invasive Bladder Cancer (BL-E 3 of 6)	Recurrent or Persistent Disease (BL-11)

表 4
Test	Year	Year	Year	Year	Year	Year
Test	1	2	3	4	5	5-10
Cystoscopy	3,6,12	Every 6 mo	Annually	Annually	As clinically indicated
Upper tract and abdomen/pelvis imagingd	Baseline imaging	As clinically indicated
Blood tests	N/A	N/A	N/A	N/A	N/A	N/A
Urine tests	Urine cytology 3,6,12	Urine cytology every 6 mo	Annually	Annually	As clinically indicated
Test	1	2	3	4	5	5-10
Cystoscopy	Every 3 mo	Every 3 mo	Every 6 mo	Every 6 mo	Annually	As clinically indicated
Upper tract imagingd	Baseline imaging, and at 12 mo	Every 1-2 y	Every 1-2 y	Every 1-2 y	Every 1-2 y	As clinically indicated
Abdomen/pelvis imagingd	Baseline imaging	As clinically indicated
Blood tests	N/A	N/A	N/A	N/A	N/A	N/A
Urine tests	●Urine cytology every 3 mo ●Consider urinary urothelial tumor markers (category 2B)	Urine cytology every 6 mo	Annually

表 6
Test	Year	Year	Year	Year	Year	Year	Year
Test	1	2	3	4	5	5-10	>10
Cystoscopy	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Imagingd	·CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) annually	CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) annually	Renal US annuallye	As clinically indicated
Blood tests	·Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFT every 3-6 mo ●CBC,CMP every 3-6 mo if received chemotherapy	●Renal function testing (electrolytes and creatinine) annually ●LFTf annually ●B12 annually based on clinical judgment	B12 annually based on clinical judgment
Urine tests	·Consider urine cytology every 6-12 mo ●Consider urethral wash cytology every 6-12 mo9	Urine cytology as clinically indicated Urethral wash cytology as clinically indicated
Test	1	2	3	4	5	5-10	>10
Cystoscopy	N/A	N/A	N/A	N/A	N/A	N/A	N/A
Imagingd	●CTU or MRU (image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo ●CT chest (preferred) or chest x-ray annually or every 3-6 mo ●FDG-PET/CT (category 2B) only if metastatic disease suspected	●Abdomen/pelvis CT or MRI annually ●CT chest (preferred) or chest x-ray annually or ●FDG-PET/CT (category 2B) only if metastatic disease suspected	Renal US annually e	As clinically indicated
Blood tests	●Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFTf every 3-6 mo ●BCT2 every 3-6 mo 3-6 mo if received chemotherapy	●Renal function testing (electrolytes and creatinine) annually ●LFTf annually by 12 annually based on clinical judgment	Renal US annually e	As clinically indicated
Urine tests	●Consider urine cytology every 6-12 mo ●Consider urethral wash cytology every 6-12 mo9	Urine cytology as clinically indicated Urethral wash cytology as clinically indicated
Test	1	2	3	4	5	5-10	>10
Cystoscopy	Every 3 mo	Every 3 mo	Every 6 mo	Every 6 mo	Annually	Annually	As clinically indicated
lmagingd	●CTU or MRU (image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo for MIBC ●CT chest (preferred) or chest x-ray every 3-6 mo for MIBC ●FDG-PET/CT (category 2B) only if metastatic disease suspected	●Abdomen/pelvis CT or MRI annually ●CT chest (preferred) or chest x-ray annually or ●FDG-PET/CT (category 2B) only if metastatic disease suspected	As clinically indicated
Blood tests	·Renal function testing (electrolytes and creatinine) every 3-6 mo ●LFT f every 3-6 mo ●CBC.MMP every 3-6 mo if received chemotherapy	●Renal function testing (electrolytes and creatinine) as clinically indicated

Urine tests	Urine cytology every 6-12 mo	Urine cytology as clinically indicated

表 9
Test	Year	Year	Year	Year	Year	Year	Year
Test	1	2	3	4	5	5-10	>10
Cystoscopy	●As clinically indicated
Imagingd	●CTU or MRU(image upper tracts + axial imaging of abdomen/pelvis) every 3-6 mo if clinically indicated and with any clinical change or new symptoms ●CT chest/abdomen/pelvis every 3-6 mo and with any clinical change or new symptoms or ●FDG-PET/CT(category 2B)
Blood tests	●CBC,CMP every 1-3 mo ●B12 annually for patients who had undergone a cystectomy based on clinical judgment
Urine tests	●Urine cytology as clinically indicated

表 10
Adjuvant Therapy	Adjuvant Therapy
No previous platinum-based neoadjuvant therapy(pT3, pT4a, pN+)	Previous platinum-based neoadjuvant therapy(ypT2-ypT4a or ypN+)
Preferred regimen	Other recommended regimen
●DDMVAC with growth factor support for 3-6 cycles1,2	●Nivolumab6
Other recommended regimens	●Pembrolizumab7
●Nivolumab6
●Pembrolizumab7

表 11
Second-Line Systemic Therapy for Locally Advanced or Metastatic Disease (Stage IV)
Previous immunotherapy and entorumab vedotin-ejfv (no previous chemotherapy)
Preferred regimens	Other recommended regimens	Useful in certain circumstances
●DDMVAC with growth factor support2	●Paclitaxel22 or docetaxel23	●Gemcitabine, cisplatin, and nivolumab (category 2B)
●Gemcitabine and cisplatin4
●Gemcitabine and carboplatin (category 2B)
●Biomarker-directed therapy (see biomarker-directed therapy table, BL-G 4 of 7)
Previous chemotherapy (no previous immunotherapy or enfortumab vedotin-ejfv)${}^{c}$
Preferred regimens	Other recommended regimens	Useful in certain circumstances-
●Pembrolizumab(category 1 post-platinum)25	●Paclitaxel22 or docetaxel23	●DDMVAC with growth factor support2
●Enfortumab vedotin-ejfv and pembrolizumab ${}^{16}$	●Paclitaxel22 or docetaxel23	(category 2B)
●Enfortumab vedotin-ejfv26		●Ifosfamide,doxorubicin,and gemcitabine30
●Nivolumab27 (category 2B)		(category 2B)
●Avelumab28,29 (category 2B)		●Gemcitabine and paclitaxel31 (category 2B)
●Biomarker-directed therapy (see biomarker-directed therapy table,BL-G 4 of 7)		●Gemcitabine and cisplatin4 (category 2B)
Previous immunotherapy (no previous chemotherapy or enfortumab vedotin-ejfv)
Preferred regimens	Other recommended regimens	Useful in certain circumstances
●Enfortumab vedotin-ejfv and pembrolizumab	●Paclitaxel22 or docetaxel23	●Gemcitabine,cisplatin,and nivolumab (category 2B)
●Gemcitabine and carboplatin		●fosfamide, doxorubicin,and gemcitabine30
●Demcitabine and cisplatin4
●DDMVAC with growth factor support2		●fosfamide, doxorubicin,and gemcitabine30 (category 2B)
●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)
Previous chemotherapy and immunotherapy (no previous enfortumab vedotin-ejfv)d,e
Preferred regimens	Other recommended regimens	Useful in certain circumstances
●Enfortumab vedotin-ejfv32,33 (category 1)	●Enfortumab vedotin-ejfv and pembrolizumab	●Sacituzumab govitecan-hziy34
●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)	●Paclitaxel22 or docetaxel23
●Gemcitabine and bisplatin 24
●DDMVAC with growth factor support2
●Enfortumab vedotin-ejfv32,23 (category 1)	●
●Biomarker-directed therapy(see biomarker-directed therapy table,BL-G 4 of 7)	●Paclitaxel22 or docetaxel23	●Sacituzumab govitecan-hziy34

表 12
Subsequent-Line Systemic Therapy for Locally Advanced or Metastatic Disease (Stage IV)d,e
Previous chemotherapy,immunotherapy, and enfortumab vedotin-ejfv
Preferred regimen	Other recommended regimens	Useful in certain circumstances
●Biomarker-directed therapy Biomarker-directed therapy (see biomarker-directed therapy table)	$\bullet$ Gemcitabine 24 ●Paclitaxel22 or docetaxel23 ●fosfamide, doxorubicin, and gemcitabine 30(category 2B). ● Gemcitabine and paclitaxel31 (category 2B)	$\bullet$ Sacituzumab govitecan-hzi ${}^{34}$

表 13
Radiosensitizing Chemotherapy Regimens
Preferred regimens · Cisplatinh alone37,38 ● Low-dose gemcitabine39-41 ● 5-FU and mitomycin42	Other recommended regimens · Cisplatin and 5-FU39,43 ● Cisplatin and paclitaxel39,44	Useful in certain circumstances (not generally used for curative-intent chemoradiotherapy for organ preservation) ●Taxane (docetaxel or paclitaxel) (category 2B) ●5-FU (category 2B) ●Capecitabine(category 3)

表 14
	T	N	M	T	T	N	M
Stage 0a	Ta	NO	M0		T1-T4a	N1	M0
Stage 0is	CIS	NO	M0	Stage III	T1-T4a	N2,N3	M0
(Tis)			Stage IVA	T4b	Any N	M0
Stage I	T1	NO	M0		Any T	Any N	M1a
Stage II	T2a	NO	M0	Stage IVB	Any T	Any N	M1b
	T2b	NO	MO
Stage IIIA	T3a	NO	MO
	T3b	NO	MO
	T4a	NO	MO

表 15
T	N	M
Stage 0a	Ta	NO M
Stage Ois	CIS	NO M
(Tis)		(Tis)
Stage I	T1	NO M
Stage II	T2	NO M
Stage III	T3	NO M
Stage IV	T4	NX,NO M
Any T	N1	M0
Any T	N2	M0
Any T	Any N	M1

表 16
ALT	alanine aminotransferase	MMR	mismatch repair
AST	aspartate aminotransferase	MRU	magnetic resonance
BCG	Bacillus Calmette-Guérin		urography
CAP	College of American Pathologists	NMIBC	microsatellite instability-high
CBC	complete blood count		nMIBC
CIS	carcinoma in situ	NOS	not otherwise specified
CLIA	Clinical Laboratory	PA	posteroanterior
Improvement Amendments	Improvement Amendments	PSA	prostate-specific antigen
CMP	comprehensive panel	RT-PCR	reverse transcriptase polymerase chain reaction
CNS	central nervous system	TUR	transurethral resection
ctDNA	circulating tumor DNA	TUR	transurethral resection of bladder tumor
CTU	computed tomography urography	TURP	transurethral resection of the prostate
CTV	clinical target volume	UTUC	upper tract urothelial cancer
DRH	dose-volume histogram
EBRT	external beam radiation therapy
EUA	examination under anesthesia
FDG	fluorodeoxyglucose
GFR	glomerular filtration rate
GU	genitourinary
H&P	history and physical
IHC	immunohistochemistry
IVP	intravenous pyelogram
LFT	liver function test
MIBC	muscle-invasive bladder cancer

表 17
MMR	mismatch repair magnetic resonance urography
MSI-H	microsatellite instability-high
NMIBC	non-muscle-invasive bladder cancer
NOS	not otherwise specified
PA	posteroanterior
PSA	prostate-specific antigen
RT-PCR	reverse transcriptase polymerase chain reaction
TUR	transurethral resection
TURBT	transurethral resection of bladder tumor
TURP	transurethral resection of the prostate
UTUC	upper tract urothelial cancer

表 18
NCCN Categories of Evidence and Consensus
Category 1	Based upon high-level evidence (≥1 randomized phase 3 trials or high-quality, robust meta-analyses), there is uniform NCCN consensus(≥85% support of the Panel) that the intervention is appropriate.
Category 2A	Based upon lower-level evidence, there is uniform NCCN consensus(≥85% support of the Panel) that the intervention is appropriate.
Category 2B	Based upon lower-level evidence, there is NCCN consensus(≥50%, but <85% support of the Panel) that the intervention is appropriate.
Category 3	Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

表 19
NCCN Categories of Preference
Preferred intervention	Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.
Other recommended intervention	Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data; or significantly less affordable for similar outcomes.
Useful in certain circumstances	Other interventions that may be used for selected patient populations (defined with recommendation).

图示：CLINICAL PRESENTATION EVALUATIONa PRIMARY EVALUATION/SURGICAL TREATMENT PRESUMPTIVE CLINICALA CLINICALB R1P ADDITIONAL STAGINGWORKUP STAGEf,9 Non-muscle-invasive bladder cancer(NMIBC)cisternia(EUA)(bimanual) TURBtd Non-muscle-invasive bladder cancer(NMIBC)cisternia CIS Stage II(cT2, N0)h BL-5 Stage IIIIA (cT3, N0;cT4a,N0;cT1-T4a,N1)'h Stepive LIEB BL-7 Stage IIIIB (cT1-T4a,N2,3)h Bl-8 Stage III Stepive LIEB Metastatic(Stage IVB Any T, Any N, M1b) BL-10 Pransse PRESUMPTIVE CLINICALA CLINICALB R1P Stage II4(cT3, N0;cT4a,N0;cT1-T4a,N1)'h Bl-8 Stage III Stepive LIEB (cT3, N0;cT4a,N0;cT1-T4a,N1)'h Bl-8 PPT4d Stage II(BL-5 PPT6 Stage III(ICT4, N0); Stage III Stage III Stage III PPT8 Metastatic(Stage IVB Any T, Any N, M1b) BL-8 10 AV AT.7 AV NY1)

图示：Initial TURBT shows NMIBC or Visually complete resection Visually complete resection High-grade NMIBC High-grade NMIBC and JAL Carcinoma in situ(CIS) or Tai Carcinoma in NMCIB T1 or consider for select Taj Residual NMIBC or no residual cancer Visually incomplete resection High-volume tumorii

图示：AUA RISK GROUP (BL-2) Low Intermediate Intravesical therapy P,q (preferred) prferred) or (Surveillance Cystectomy (preferred) Bacillus Calmette-Guérin (BCG) naive High Bacillus Calmette-Guérin (BCG) naive Risk features No very-high-risk features Very-high-risk Nocableprint's Nocystectomy (preferred) BCGG Pystectomy 1, preferred) High Cystectomy (preferred) Intravesical chemotherapyP or or or Surveillance Cystoscopy negative BL-4 BL-4 ALA Risk and Group and manage accordingly BBCG unresponsive BCG intolerant Nodofaragene firadenove-cvng (select patients)t or Nogapendekin alfa inbakicept-pmln + BCGU (select patients)s Bembrolizumab (select patients)s,nn Nodafaragene firadenove-cvng (select patients)t Pembrolizumab (select patients)s,nn

图示：RECURRENT OR PERSISTENT DISEASE FOLLOW-UP RESULTS EVALUATION PERSISTENT DISEASE FOLLOW-UP RESULTS RESULTS Cancer Consider: Repeat cytology within 3 months Selected mapping biopsies including transurethral biopsy of prostate Bladder positive Prostate positive Reclassify AUA Risk Group and manage accordingly (BL-3) II(1-251-4000-254000-253000-268000-240000-2711 Clystology Inaging negative Ureteroscopy Enhanced cystoscopy v(if available) Non-urinary tract source (eg, vagina, cervix, rectum) and referral to gynecology or other specialist, as appropriate Upper tract positive Urothelial Carcinoma of the Prostate(UCP-1) Upper tract tract DUTT Tumors (UTT-1)

图示：CLINICAL ADDITIONAL STAGINGh WORKUPc Reoadjuvant cisplatin-based combination chemotherapy^{2} or perioperative/sandwich immunotherapy and with neoadjuvant cisplatin-based combination chemotherapy^{2} followed by radical cystectomyd2 (category 1) Abdomen/pelvis CT or MRI if not previously done Bone scan or MRIX if clinical suspicion or symptoms of bone metastases Estimate glomerular filtration rate (GFR) to assess eligibility for cisplatinY Or Reassess tormative therapy or Bladder deflection Chodder preservation with concurrent chemotherapyua,bb,cc (category) If cis, Ta, or T1, consider TURBT +/-intravesical therapyplab cansy thorted population Asdujant-treatment Adjuvant Treatment (BL-6) Adjuvant Treatment (BL-6) Addujant Treatment (BL-6) Addujant Treatment (BL-6) Tumor Tumor For Cystectomy alone for those not eligible to receive cisplatin-based chemotherapy or Bladder preservation AAdjuvant therapyaa,bb,cc (category) Reassess tumor status 2-3 months treatment 1) and maximal TURBT If patient is not a candidate for cystectomy or definitive chemoradiotherapy: RTbb Asdujant Tothemol Adoujum Rassess tumor status 2-3 months after treatment completionbb Tumor Asdujumou Tothemol Rassess tumor on highly selected cases)' Treat as metastatic disease (BL-10) Follow-up(BL-E)

图示：If gemcitabine + cisplatin + durvalumab given preoperatively, then durvalumab should be used postoperatively. ● Based on pathologic risk, If no cisplatin neoadjuvant treatment given and pT3, pT4a, or pN+ ● Adjuvant cisplatin-based chemotherapy should be discussed (preferred)zor ● Consider adjuvant nivolumabee or pembrolizumabz,ee or If cisplatin neoadjuvant chemotherapy given and ypT2-ypT4a or ypn+, Consider nivolumabe ee or pembrolizumabz,ee ) Consider adjuvant RT in selected patients (pT3-4, positive nodes/margins at the time of surgery)bb (category 2B)

图示：CLINICAL STAGING^{\hbar} 440N& WORKUPc ADdejuvant cisplatin-based combination chemotherapy^{\circ} or perioperative/sandwich immunotherapy with neoadjuvant cisplatin-based combination chemotherapy^{\circ} 2 or plus inseted cisplatin-based combination chemotherapy^{\circ} 2 for related by radical cystectomyd,ff (category 1) Adjuvant Treatment (BL-6) OR Pachasing CTCT 49 of bone metastases Susps ●Estimate GFR to assess eligibility For patient is not a candidate for cystectomy or definitive For patient is not chemoradiotherapy:RT^{\circ} O Pachasing CTCT 49 of bone metastases ●Estimate GFR to for cisplatin Acc.8 NCCN National Guidelines Version 2.2025 NCCN NCCN Cancer-Invasive Bladder Cancer Muscle-Invasive Bladder Cancer STAGING^{\circ} 440N& WORK Abdovular cisplatin-based chemotherapy^{\circ} 2 for different clinical therapy ●9 Aschologres 49 of bone metastases ●Estimate GFR to assess eligibility For patient is not a candidate for cystectomy or definitive ●9 Cystectomy for derivative For patient RBT TURB± intravesimal therapy ●3 Dustginal Pprinciples of Imaging for Bladder/Urothelial Cancer (BL-A) The modifier "c" refers to clinical staging based on bimanual EUA, endoscopic surgery (biopsy or TUR), and imaging studies. The modifier "p" refers to pathologic staging based on cystectomy and lymph node dissection. AC Optimal candidates for bladder preservation at with chemoradiotherapy include: Co 2B). For patients with borderline Therapy (BL-F). 2 XConsider FDG-PET/CT scan (skull base to mid-thigh) (category 2B). YFor patients with borderline GFR, consider timed urine collection, which may more accurately determine eligibility for cisplatin. 2Principles of Systemic Therapy (BL-G 1 of 7). 2Principles of Systemic Therapy (BL-G 1 of 7). Principles of Systemic Therapy (BL-G 2 of 7). Principles of Systemic Therapy and have a response factor 2B. Proinciples of Systemic Therapy (BL-G 2 of 7). Principles of Systemic Therapy and have a response factor 2B. Reessess tumor status completion bb ■ ■Surveillance No tumor tumor ■ |Surveillance ■Systemic therapy^# 2-3 months after treatment ■Systemic therapy^# 2B. ■TURB± intravavesical therapy^# 0 ■TURB+ intravavesical therapy^# 2B. Best supportive care (NCCN Guidelines for Palliative Care) ■Optimal candidates for bladder preservation with chemoradiotherapy include: Co 2B. patients with tumors that present without moderate/severe hydronephrosis, are without concurrent extensive or multifocal CIS, and are <6 cm. Ideally, tumors should allow a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-G 2 of 7). 3 Report Vortical Therapy p2 Top-RURB± intravavesical therapy^# 2B. Best supportive care (NCCN Guidelines for Palliative Care) Optimal candidates for bladder preservation with chemoradiotherapy include: Co 2B. without concurrent extensive or multifocal CIS, and are <6 cm. Ideally, tumors should allow a visually complete or maximally debulking TURBT. See Principles of Radiation Management of Invasive Disease (BL-H). 3 Follow-up(BL-E) In the following literature 2.2025, 10/10/25 @ 2025 National Comprehensive Cancer Network® (NCCN"), All rights reserved. R

图示：National Comprehensive Cancer Network®

图示：CLINICAL STAGINGh WORKUP^{C} ADDITIONAL WORKUP^{C} PREMIARYTREATMENT DOWNED Systemedgammadd Adbodomen/Pelvis CT or MRI*if not previously done Systaciony#if non MRI*if not previously previously done Systaciony#if non PriKINGH Abdomen/Pelvis CT or MRI*if Systemic therapydd Complete response Consolidation cystectomy Consolidation chemoradiotherapyaa,bb or Follow-up(BL-E) Rovance24 Progression→ Treat as metastatic disease (BL-10)

图示：Abdomen/pelvis CT or MRI× if not previously done CT1- cT4a,N2,3) Symptoms b Principles of Radiation Management of Invasive DIREngability Partial response Cystectomy“aa,bb Consolidation cystectomy Consolidation or chemoradiotherapyaa,bb or or Surveillance Follow-up Partial response Cystectomy or Chemoradiotherapyaa,bb DLI-E) Follow-up BLICE 8(BL-E) Abdomen/pelvis CT or membrane Status 2-3 months after treatmenth d treatmenth Progression → Treat as metastatic disease (BL-10)

图示：Recurrent or Persistent Disease(BL-11)

图示：CLINICAL STAGINGh ADDITIONAL WORKUPC PRIMARY TREATMENT No tumor After 2-3 cycles, reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy No tumor Chemoradio- and/or Follow-up Follow-up (BL-E) ADdomen/pelvis CT or MRI× not previously done ● Chest imaging (CT chest) MONO disease M0 disease Concurrent chemoradiotherapyaa,bb 32 No tumor After 2-3 cycles, reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy To assess using imaging M1a disease → Systemic therapydd Systemic therapydd and imaging of abdomen/pelvisc Tumor Non to 23 - cycles, reassess with reassess with cystoscopy, EUA, TURBT, and imaging of abdomen/pelvis cystoscopy To 23 32 433.19 Systemic therapydd and imaging of abdomen/pelvisc M1a disease →Systemic therapydd and imaging of abdomen/pelvis cystoscopy To 23 32 433.19 Systemic therapydd and imaging of common periodic therapy Follow-up PUE (BL-E)

图示：Bone scan or MRI if clinical suspicion or symptoms of bone metastases Chest CT Consider central nervous system CNS) imagingC Estimate GFR to assess eligibility for cisplatin |Systemic therapy dd,kk d/or Palliative RTbb Follow-up Palliative BL-E)

图示：Muscle invasive or selected metastatic disease treated with curative intent Follow-up(BL-E) Preserved bladder Cytology positive Imaging negative Cystoscopy negative Metastatic or local recurrence local recurrence postcystectomy BL-10 ppr# cc|Systectomy ppr#Cystectomy R104 No Cystectomy,d,w nn1 ro|Bodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder Lodder

图示：WORKUP PRIMARY TREATMENT^d Endoscopic resectione±postsurgical intrapelvic chemotherapy or or parenchymal in invasion Nephrouterrectomy with perioperative intravesical chemotherapy Adjuvant Treatment and Discussion Low gradec Renal pelvis Imaging of upper tract collecting systema· Cytology· Ureteroscopy and biopsy or percutaneous biopsy and/or selective washings Non-metastatic High grade,cl large,or parenchymal invasion Nephrouterrectomy with perioperative intravesical chemotherapyf An Treatment and Discussion Adjuvant Treatment and Contents Discussion Renal pelvis TREATMENT PRIMARY TREATMENT Endoscopic resectione±postsurgical intrapelvery chemotherapy of or parenchymal and chemotherapy of chemotherapy Nephroureterectomy with cuff of bladder +regional lymphadenectomy ± perioperative intravesical chemotherapyf and cisplatin based neoadjuvant chemotherapy9in selected patients Metastatic Systemic therapyhym High grade,c large,or parenchymal invasion Nephrouterrectomy with cuff of bladder output and general treatment. Mitomycin for pyelocaliceal application may be administered via ureteral catheter or a nephrostomy tube. 4 3 4 5 6 7 8 9 6 3 4 5 6 Institute\mathttan ararctivesd penual Open $$\text{In aumary in Urothe7}\text{In}$$In aum.4 3 4 5 6 4 5 6 3 4 5 6 In aum.4 6 3 4 5 6 4 5 6 3 4 5 6 In aum.5 NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal. Endometrial, and Gastric-Criteria for the Evaluation of Lynch Syndrome Based on Personal or Family History of Cancer. Montironi R, Lopez-Beltran A. The 2004 WHO classification of bladder tumors: A summary and commentary. Int J Surg Pathol 2005;13:143-153. See Principles of Pathology Management(BL-C). Principles of Sympal Management(BL-B). gPrinciples of Systemic Therapy(BL-G1 of 7 Principles of Systemic Therapy(BL-G1 of 7 Principles of Systemic Therapy(BL-G1 of 7 Principles of Systemic Therapy(BL-G1 of 7 This systemic therapy's Unplature 2022, 10/10/25 @2025 National Comprehensive Cancer Network®(NCCN®),All rights reserved.NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.

图示：WORKUP Imaging of upper tract collecting system × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × × ← >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >-

图示：Adjuvant treatment for renal pelvis and urothelial carcinoma of the ureter pT0, pT1 pT0, pT3, pT4, pN+ Non None PTO, pT1 If no platinum neoadjuvant treatment given and pT3,pT4, or pN+ Adjuvant platinum-based chemotherapy should be discussed9,j or 2B) Consider adjuvant nivolumab$g, j, k\ (Catérata 4pT4, pN+ R

图示：Urothelial carcinoma of the prostate carcinoma of the prostate Digital rectal examination (DRE) ● Digital rectal examination (DRE) or prostate to include stroma stroma stroma ● Prostate-specific antigen (PSA) ● Needle biopsy if ● Prostate at problems) ● Needle biopsy if ● Imaging of upper tract collecting system prostate at upper distance in the 2970s with 2000009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500009980500

图示：Urothelial carcinoma of prostate UCP-1 Urothelial carcinoma of prostate UCP-2 Primary carcinoma of non-prostatic male urethra or female urethra UCRAP DiAGNOSIS Susicion of carcinoma of the urethra Cystourethroscopy EUA TUR or transvaginal biopsy Chest x-ray or CT MRI of pelvis with and without contrastb Urothelial Cancer of prostate of cST or or CTER SiC Ta, T1 UCRAP CIS Ta, T1 PCU-2 T3, T4 Palapable inguinal lymph nodes Distant metastasis PCU-3

图示：T2 Female Female Female

图示：National Comprehensive Currenta 构号 NCCN 2025 NCCN 2025 NCCN 2025 Primary Carcinoma of the Urethra NCCN Guidelines Version 2.2025 SUNCC Current 2025 Primary Carcinoma of the Urethra

图示：CLINICAL STAGING ADDITIONAL WORKUP CNO T3, T4 Palpable inguinal Chest/abdomen/lympelis CT with contrast nodes CN2 Surgery alone for non-urothelial histology PRIMARY TREATMENTC Chemoradiotherapy9,h(preferred)±consolidative surgery or Neoadjuvant chemotherapy1,o (if urothelial carcinoma) and consolidation with surgery or RTH or RTHth Surgery alone for non-urothelial histology Follow-up→Recurrence→ imaging HPLG Retourghk → 依 Pelvic exenteration(category 2B) ±ilioinguinal lymphadenectomy Surgery algorithm → 依题意 Pelvicexenteration(category 2B) lymphadenectomy and/or Chemoradiotherapy9,h →Systemic therapy J,l± sonidative surgery Systemic therapy j,l± sonidative surgery or NLP Surgery ertual cRNA or Metastatic Disease (BL-10)

图示：Distant metastasis Metastatic Disease(BL-10)

引用 / 出处

（2025.V2）NCCN临床实践指南：膀胱癌. 2025.

（2025.V2）NCCN临床实践指南：膀胱癌

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Version 2.2025 Bladder Cancer

RISK STRATIFICATION OF NMIBC

MANAGEMENT PER NMIBC RISK GROUP

NCCN Guidelines Version 2.2025 Management of Positive Urine Cytology

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

NCCN Guidelines Version 2.2025 Muscle-Invasive Bladder Cancer

PRINCIPLES OF PATHOLOGY MANAGEMENT

2022 WHO Classification of Tumors of the Urothelial Tract1,2

Urothelial Tumors

Squamous Cell Neoplasms

Glandular Neoplasms

Urothelial Tract Hematopoietic and Lymphoid Tumors

Miscellaneous Tumors

Urachal Carcinoma

Neuroendocrine Tumors

BLADDER CANCER: NON-UROTHELIAL AND UROTHELIAL WITH SUBTYPE HISTOLOGY

Mixed Histology:

Pure Adenocarcinoma Including Urachal Carcinoma:

Aggressive Subtype Histologies:

Pure Small Cell Carcinoma or Mixed Histology with Any Small Cell Component(or neuroendocrine features):

Primary Bladder Sarcoma:

Pure Squamous Carcinoma:

FOLLOW-UP

NCCN Guidelines Version 2.2025 Bladder Cancer

FOLLOW-UP

NCCN Guidelines Version 2.2025 Bladder Cancer

FOLLOW-UP

FOLLOW-UP

NCCN Guidelines Version 2.2025 Bladder Cancer

FOLLOW-UP

NCCN Guidelines Version 2.2025 Bladder Cancer

FOLLOW-UP

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY

Footnotes

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY

NCCN Guidelines Version 2.2025 Bladder Cancer

PRINCIPLES OF SYSTEMIC THERAPY-REFERENCES

NCCN Guidelines Version 2.2025 Upper GU Tract Tumors

NCCN Guidelines Version 2.2025 Upper GU Tract Tumors

PATHOLOGIC ADJUVANT TREATMENT STAGING

FOLLOW-UP

NCCN Guidelines Version 2.2025 Urothelial Carcinoma of the Prostate

NCCN Guidelines Version 2.2025 Primary Carcinoma of the Urethra

NCCN Guidelines Version 2.2025 Primary Carcinoma of the Urethra

NCCN Guidelines Version 2.2025 Bladder Cancer

NCCN Guidelines Version 2.2025 Bladder Cancer

TNM Staging System for Renal Pelvis and Ureter Cancer (8th ed., 2017)

N Regional Lymph Nodes

M Distant Metastasis

Histologic Grade(G)

Table 4. AJCC Prognostic Groups

NCCN Guidelines Version 2.2025 Bladder Cancer

ABBREVIATIONS

NCCN Guidelines Version 2.2025 Bladder Cancer

相关指南

引用 / 出处