2025 CCA指南：成人癌痛的管理（更新版）

ABSTRACT

Aims: The Cancer Council Australia Cancer Pain Management in Adults Clinical Guideline aimed to inform timely, evidence-based guidance for managing cancer-related pain.

Methods: The ADAPTE approach for guideline updates was adopted. Source guidelines were selected following the AGREE II criteria. The target population was adults with chronic cancer-related pain. The interventions were screening, assessment, and management of cancer-related pain. Target users and settings were all health professionals caring for adults with cancer in any healthcare setting. Outcomes are reduction in cancer-related pain.

Results: Recommendations were mostly adopted directly from source guidelines and the recommendation strength reflected those of the source guidelines. Those which were developed de novo were either based on Level 1 evidence or consensus within the context of a documented need in the Australian setting.

Conclusions: The Cancer Council Australia guideline for managing cancer pain in adults contains evidence-based recommendations to guide appropriate evidence-based care.

1 | Introduction

An estimated 45% of people with cancer experience pain [1]. In 1986, the World Health Organization (WHO) released the first global guideline on the management of cancer pain

[2]. Since then, a large number of guidelines have become available internationally [3-8]. Research has demonstrated that implementing evidence-based clinical practice guidelines for cancer pain can improve care and patient outcomes [9].

The updated Australian Cancer Pain Management in Adults Clinical Guideline was published online on June 12, 2024 [10] when a new online guideline platform was launched. A previous article reported the process used to develop the original 2013 guideline but not the guidelines' recommendations [11, 12]. Both the original guideline adaptation and update followed the ADAPTE process to adapt international guidelines for the Australian setting rather than develop de novo recommendations [13]. The most recent update included moving the guideline to the MAGICApp platform to enhance the user interface [14].

2 | Aim of the Australian Guideline

The Australian Cancer Pain Management in Adults Clinical Guideline, hereafter referred to as the guideline, aimed to inform timely, evidence-based guidance for managing cancer-related pain. It was initiated in response to a need identified by Australian health professionals and government [11, 12, 15]. In the current policy environment, guidelines are essential to advocate for the availability of opioids for cancer pain management and to provide a reliable source of information to guide prescribing. The inappropriate use of opioids in chronic pain management has resulted in government warnings intended to reduce net harm associated with this indication. These warnings have had the unintended consequence of raising concern about prescribing opioids in other settings, including for the relief of cancer-related pain where the evidence-base and guidelines support their use. Thus, the guideline plays a critical role in supporting appropriate prescribing and providing education on best evidence-based practice for cancer-related pain management. There is also a need to highlight the important role played by nonpharmacological strategies in the management of pain, which is often overlooked.

3 | Target Population

This guideline sought to provide concise, point-of-care recommendations for screening, assessment, and management of cancer-related pain in adults. Its focus is on chronic pain associated with cancer, rather than acute pain caused by treatments or chronic pain in dise-free survivors.

4 | Target Users and Settings

This guideline is intended for all Australian health professionals caring for people with cancer in all healthcare settings.

5 | Methods

5.1 | Working Party and Expert Advisory Panel

The Working Party included original members who developed the first version of the guideline as well as new members. The group included three palliative care physicians, two medical oncologists, an implementation scientist, an academic nurse, a consumer, a radiation oncologist, and two specialist pain medicine physicians. The group met twice and conducted discussion via email between meetings. Expert Advisory Panel reviews

BOX 1 | PIPOH for guideline development

|Population|People with chronic cancer-related pain| |---|---| |Intervention|Screening, assessment, management of cancer-related pain| |Professions|All health professionals looking after people with cancer| |(target users)|Reduction in cancer-related pain,| |Outcomes|guideline adherence| |Healthcare|Primary care, specialist cancer services,| |setting|palliative care|

were conducted for key sections requiring additional review by two pharmacists, a pharmacologist, a dual trained medical oncologist and palliative care physician with expertise in pharmacogenomics, and a palliative care physician with specific expertise in neuropathic cancer pain. A postdoctoral research fellow with a medical background in general practice (primary care) provided project support. Participants were selected to ensure broad interdisciplinary representation. Each group member reviewed recommendations within their fields of expertise.

The ADAPTE approach [14] for guideline updates was adopted. Reporting of the guideline update is guided by the RICHT-Ad@pt Checklist [16].

5.2 | Source Guidelines

Guidelines were included based on the agreed Population, Intervention, Professions, Outcomes and Health care system (PIPOH) outlined in Box 1 and requirements for currency and evidence using the Appraisal of Guidelines Research and Evaluation Instrument (AGREE II) criteria [17]. To be included as sources, guidelines had to have a primary focus on adults with chronic cancer pain, relevance across tumor types and stages, inclusion of recommendations for assessment and/or management of pain by pharmacological or nonpharmacological interventions, capacity to be used in an interdisciplinary setting, be published in the previous 7 years, have national or international coverage, be available in English, and be independently rated as "recommended" or "strongly recommended" by two members of the Working Party based on AGREE II criteria. New guidelines considered as sources in the update that had not been available when the original guidelines were adapted were the World Health Organization (WHO) (2018) Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents [6] and American Society of Clinical Oncology (ASCO) publication in 2016 entitled Management of Chronic Pain in Survivors of Adult Cancers [7]. Previously, the guideline development group had referenced the Scottish Intercollegiate Guideline Network (SIGN) and the European Association of Palliative Care (EAPC) but, in the absence of updates from these organizations, these were no longer included.

For the 2019 guideline update, in order to include recommendations from new editions of the source guidelines or new guidelines that met criteria for quality and applicability, a comprehensive

BOX 2 | Key questions addressed in the guideline

How should a comprehensive assessment of cancer pain be conducted?

What self-management and nonpharmacological strategies for pain in people with cancer are effective?

Which pharmacological treatment should be initiated and titrated for cancer-related pain including breakthrough pain, neuropathic pain, and bone pain?

How should treatment be modified in people with renal impairment?

How should potential adverse effects be prevented and managed?

What interventional pain management strategies are effective for cancer pain?

What cancer-directed therapies are effective for cancer pain?

Is pharmacogenomic testing recommended prior to cancer pain management?

search was undertaken in January 2019. A series of Medline searches using keywords for cancer, pain, opioids, NSAIDs, acupuncture and constipation, and limiting to reviews, randomized controlled trials, humans, adults, and English-language were undertaken to identify articles published since first June 2015.

The following guidelines (Box 2) met all criteria and were considered for adaptation in the 2024 revision, and the authors of all these guidelines were contacted.

The source guideline which was adopted and adapted for the Australian guideline is noted for each recommendation.

5.3 | Key Questions

Key questions were constructed to address screening, assessment, and management of cancer pain (Box 3).

5.4 | Source Recommendations and Evidence Synthesis

Source recommendations were tabulated within a matrix against the key questions. Updates in the source guidelines were identified. Draft recommendations were presented to the Working Group and Expert Advisory Panel. The Working Group and the Expert Advisory Panel feedback was discussed via email and incorporated into the guideline updates. The recommendations were then endorsed by the Working Group and Expert Advisory Panel. The adapted recommendations were based on the existing evidence from the source guideline. The source of each recommendation was identified in the updated guideline.

BOX 3 | Guidelines included in the update

National Institute of Health and Care Excellence Guideline Development Group. Palliative Care for Adults: Strong Opioids for Pain Relief. NICE Clinical Guideline WHO Guidelines 2016

Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology (ASCO) Clinical Practice Guideline 2016

Management of Cancer Pain in Adult Patients: European Society of Medical Oncology (ESMO) Clinical Practice Guidelines 2018

World Health Organization (WHO) Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents 2018

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Adult Cancer Pain 2023

Use of Opioids for Adults with Pain from Cancer or Cancer Treatment: ASCO Guideline. 2023

6 | Results

Recommendations were mostly adopted directly from source guidelines and the recommendation strength reflects those of the source guidelines. Those which were developed de novo were either based on Level 1 or consensus within the context of a documented need in the Australian setting. For example, occupational therapists can assess and support activities of daily living, energy conservation, anxiety management, relaxation, and provide diversional therapy, splints, role support, advice on functional ability, positional and seating assessment and advice, wheelchair, assistive equipment, and home modifications. While no international guideline mentions occupational therapists, in Australia, occupational therapists are considered core members of the multidisciplinary team, and so a related recommendation was drafted [10]. Recommendations are listed in Tables 1 and 2.

7 | Discussion

The robust adaptation process enabled publication of recommendations to guide clinicians in managing cancer-related pain. Further research could examine extending the guideline to be suitable for the Oceanic region or exploring the utility of the guideline in supporting policy and practice in low- and middle-income countries in our region especially with respect to opioid availability to meet the need for optimal, evidence-based cancer-related pain management.

Implementation strategies and knowledge translation plans are needed for guideline adoption and adherence [18]. The challenges for implementing cancer pain guidelines even in Australia are well documented [19, 20]. Implementation frameworks such as the Capability, Opportunity and Motivation Behaviour (COM-B) Model provide a structured approach to identifying factors which influence behavior and ways to mitigate or leverage these. Extensive stakeholder engagement in the development of clinical

TABLE 1 | Recommendations for person-centered care, screening, assessment, self-management, and nonpharmacological strategies for cancer-related pain.

|Domain|Recommendation ID|Recommendation| |---|---|---| |Person-centered care (PCC)|PCC1|Adopt a person-centered approach to pain management (NICE, NCCN), which: takes into account the person's needs and preferences; involves the person in developing treatment plans and setting meaningful, realistic expectations and measurable functional goals; enables the person to make informed decisions about their care and treatment; provides culturally safe assessment, care and information involves the person's partner, carer, or family in treatment decisions, if the person wishes.| |PCC2|Routinely establish a multidisciplinary team approach to pain management that involves allied care health professionals and primary care health professionals according to the person's pain management needs and preferences. (NCCN)|Routinely establish a multidisciplinary team approach to pain management that involves allied care health professionals and primary care health professionals according to the person's pain management needs and preferences. (NCCN)| |Screening (S)|S1|For people who can communicate their level of pain: At each clinical encounter, assess current, worst, least, and average pain intensity during the previous 24 h using a self-reported (NCCN, ESMO): numerical rating scale from 0 to 10, where 0 represents "no pain" and 10 represents "worst pain you can imagine";| |S2|S2|Categorical scale such as "nil," "mild" (corresponding to 1–3), "moderate" (4–6), "severe" (7–10), or faces pain rating scale.| |Assessment (A) How should a comprehensive assessment of cancer pain be conducted?|A multi-faceted approach is recommended that combines direct observation, family/caregiver input, and evaluation of response to pain medicines or nonpharmacological interventions. (NICE)|A multi-faceted approach is recommended that combines direct observation, family/caregiver input, and evaluation of response to pain medicines or nonpharmacological interventions. (NICE)| |Assessment (A)|A1|Al Complete a comprehensive assessment if either of the following apply: if the person reports a pain score of 2 or more on a self-reported numerical rating scale of 0–10, or pain-related behaviors or discomfort in people with cognitive impairment (see Screening); if the person reports a new pain or a sudden, unexpected change in the intensity of pain. (Consensus) Assess all the following to determine the individual's pain management needs. The assessment should characterize the pain, clarify its etiology, and make inferences about pathophysiology. Assessment will include: Disease status and treatment; (Consensus) Pain severity (using a validated tool); (NCCN) Pain experience (location, interference, timing, description, aggravating and relieving factors, and associated distress); (ESMO, NCCN) Current and previous management of pain including adverse effects of analgesics (ESMO, NCCN) and other symptoms; (Consensus) Pain meaning for the person and their beliefs and knowledge (NCCN), including concern about pain and its treatment (e.g., perceived addictiveness of opioids); (NICE)| |Psychosocial status; (ESMO, NCCN) Risk factors for opioid misuse; (NCCN) Cognitive functioning; (Consensus) Physical examination and, where needed, further investigations; (NCCN)|Psychosocial status; (ESMO, NCCN) Risk factors for opioid misuse; (NCCN) Cognitive functioning; (Consensus) Physical examination and, where needed, further investigations; (Continues)|Chinues|

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TABLE 1 | (Continued)

|Domain|Recommendation|Recommendation|Recommendation| |---|---|---|---| |Domain|Recommendation ID|Recommendation|Recommendation| |Domain|Functional status; (ESMO)Risk factors for poorly controlled pain including nonadherence to pain management strategies; (NCCN)Patient and family preferences (goals and expectations for comfort); (NCCN)Cultural factors; (NCCN)Factors suggesting an oncological emergency. (NCCN)Reassess whenever there is a change in pain or a new pain is reported.||| |Self-management (SM) and other nonpharmacological (N) evidence-based strategies|||| |What self-management and nonpharmacological strategies for pain in people with cancer are effective?|||| |Self-management (SM) SM1 SM1 Patients with pain should be provided with verbal and written information on pain and its management, including:pain causes;common experiences of cancer pain and pain is different for everyone (e.g., onset, timing);effective treatments (including medicines and nonpharmacological management strategies);effect of medicines including breakthrough analgesia (e.g., onset and duration of effect; when to take them);side-effects of medicines such as opioid-related constipation and how to prevent or manage them;any safety concerns (e.g., mixing with alcohol, driving);ways to ensure patients have adequate access to and supply of prescribed opioids;how to work with health professionals to achieve the best pain control possible (e.g., the importance of reporting rather than concealing pain, side-effects, and other concerns about medication);common attitudes and beliefs that may prevent people with cancer from receiving effective pain control (e.g., fears that opioids are addictive and used only at the end-of-life, and that patients will develop tolerance over time requiring dose escalation);when to seek help (e.g., if vomiting and unable to keep down fluids for 1 day, bowels not open 3 days,new pain, change in pain, or pain not relieved by medication, difficulty arousing the patient from sleep easily during the daytime, confusion, difficulty accessing the medications). (Consensus)Include the person's family, carers, and significant others in education about pain and its management,if appropriate. (Consensus)Optimize the use of evidence-based nonpharmacological strategies for all people with cancer-related pain. See recommendations on self-management.Modalities recommended in international guidelines:Acceptance-based training (NCCN); Acupuncture (ASCO); Bed/bath/walking aids (NCCN);Biofeedback (NCCN); Cognitive-behavioral therapy (NCCN); Distraction therapy (NCCN); Energy conservation (NCCN); Exercise: therapeutic and conditioning (NCCN); Graded task assignment, setting goals, pacing, prioritizing (NCCN); Heat/ice therapy (NCCN); Imagery/hypnosis (NCCN); Massage (NCCN); Mindfulness-based stress reduction (NCCN); Transcutaneous electrical nerve stimulation (TENS) (NCCN); Relaxation (NCCN); Ultrasonic stimulation (NCCN)Consider referral to a physiotherapist for assessment of functional ability and provision of exercise and other physical strategies including treatment of lymphoedema. (NCCN)Provide support for any psychosocial and spiritual concerns identified during comprehensive assessment which may be contributing to cancer-related pain. (NCCN)|||| |Self-management (SM) SM1 SM1 Patients with pain should be provided with verbal and written information on pain and its management, including:pain causes;common experiences of cancer pain and pain is different for everyone (e.g., onset, timing);effective treatments (including medicines and nonpharmacological management strategies);effect of medicines including breakthrough analgesia (e.g., onset and duration of effect; when to take them);side-effects of medicines such as opioid-related constipation and how to prevent or manage them;any safety concerns (e.g., mixing with alcohol, driving);ways to ensure patients have adequate access to and supply of prescribed opioids;how to work with health professionals to achieve the best pain control possible (e.g., the importance of reporting rather than concealing pain, side-effects, and other concerns about medication);common attitudes and beliefs that may prevent people with cancer from receiving effective pain control (e.g., fears that opioids are addictive and used only at the end-of-life, and that patients will develop tolerance over time requiring dose escalation);when to seek help (e.g., if vomiting and unable to keep down fluids for 1 day, bowels not open 3 days,new pain, change in pain, or pain not relieved by medication, difficulty arousing the patient from sleep easily during the daytime, confusion, difficulty accessing the medications). (Consensus)Include the person's family, carers, and significant others in education about pain and its management,if appropriate. (Consensus)Optimize the use of evidence-based nonpharmacological strategies for all people with cancer-related pain. See recommendations on self-management.Modalities recommended in international guidelines:Acceptance-based training (NCCN); Acupuncture (ASCO); Bed/bath/walking aids (NCCN);Biofeedback (NCCN); Cognitive-behavioral therapy (NCCN); Distraction therapy (NCCN); Energy conservation (NCCN); Exercise: therapeutic and conditioning (NCCN); Graded task assignment, setting goals, pacing, prioritizing (NCCN); Heat/ice therapy (NCCN); Imagery/hypnosis (NCCN); Massage (NCCN); Mindfulness-based stress reduction (NCCN); Transcutaneous electrical nerve stimulation (TENS) (NCCN); Relaxation (NCCN); Ultrasonic stimulation (NCCN)Consider referral to a physiotherapist for assessment of functional ability and provision of exercise and other physical strategies including treatment of lymphoedema. (NCCN)Provide support for any psychosocial and spiritual concerns identified during comprehensive assessment which may be contributing to cancer-related pain. (NCCN)|SM2 SM2 Use of of use of evidence-based nonpharmacological strategies for all people with cancer-related pain. See recommendations on self-management.Modalities recommended in international guidelines:Acceptance-based training (NCCN); Acupuncture (ASCO); Bed/bath/walking aids (NCCN);Biofeedback (NCCN); Cognitive-behavioral therapy (NCCN); Distraction therapy (NCCN); Energy conservation (NCCN); Exercise: therapeutic and conditioning (NCCN); Graded task assignment, setting goals, pacing, prioritizing (NCCN); Heat/ice therapy (NCCN); Imagery/hypnosis (NCCN); Massage (NCCN); Mindfulness-based stress reduction (NCCN); Transcutaneous electrical nerve stimulation (TENS) (NCCN); Relaxation (NCCN); Ultrasonic stimulation (NCCN)Consider referral to a physiotherapist for assessment of functional ability and provision of exercise and other physical strategies including treatment of lymphoedema. (NCCN)Provide support for any psychosocial and spiritual concerns identified during comprehensive assessment which may be contributing to cancer-related pain. (NCCN)|||

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TABLE 1 | (Continued)

|Domain|Recommendation|| |---|---|---| |Domain|N4|Consider referral to an occupational therapist for assessment and management. (Consensus)| |Domain|N5|Consider referral to a clinical psychologist for psychological therapies and support. (Consensus)| |Domain|N6|Consider music, either prerecorded or with a music therapist. (NCCN, ASCO 2022)| |Domain|N7|Offer to discuss any complementary therapies the person may wish to consider and provide reliable information about the evidence for their effectiveness and risks. (Consensus)|

Abbreviations: ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network; NICE, National Institute for Health and Care Excellence.

TABLE 2 | Summary of recommendations for pharmacological, interventional management, cancer-directed therapies, and pharmacogenomic recommendations.

|Domain|Recommendation|Recommendation| |---|---|---| |Domain|Recommendation|Recommendation| |Pharmacological management (P)|Pharmacological management (P)|Which pharmacological treatment be initiated and titrated for cancer-related pain including breakthrough pain, neuropathic pain, and bone pain? How should treatment be modified in people with renal impairment? How should potential adverse effects be prevented and managed?| |Pharmacological management (P)|P1|Analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate to the severity of pain. (ESMO)| |Pharmacological management (P)|P2|In adults (including older persons) and adolescents with pain related to cancer, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and opioids generally should be used at the stage of initiation of pain management, either alone or in combination, depending on the clinical assessment and pain severity, in order to achieve rapid, effective, and safe pain control. (WHO) As an alternative to weak opioids, low doses of strong opioids could be an option. (ESMO) (There is no high-quality evidence to support or refute the use of paracetamol and/or an NSAID either by themselves or in combination with opioids; however, they are recommended in source guidelines. (ESMO, NCCN)| |Pharmacological management (P)|P2|P2 If pain is constant and is moderate or severe or continues despite treatment with paracetamol or NSAIDs, consider a regular oral opioid. (ESMO, NCCN)| |Individual titration, for example, normal-release morphine administered every 4 h plus rescue doses (up to hourly) for breakthrough cancer pain is recommended in clinical practice. (ESMO) For people with intermittent pain, opioids should be initiated as immediate release and PRN (as needed) to establish an effective dose, with early assessment and frequent titration. (ASCO 2016, ASCO 2022) If 3-4 doses are needed per day consistently, consider the addition of a long-acting opioid. (NCCN) In older or frail people, starting doses should be lower. Prior to initiating opioid therapy, clinicians, people with cancer pain, and caregivers should discuss goals regarding functional outcomes, and pain intensity, as well as any concerns about opioids (ASCO 2016, ASCO 2022) and shared expectations including opioid down titration and cessation. (Consensus) For people who are candidates to begin opioid treatment, clinicians may offer any of the opioids available. Qualifying statement: The decision of which opioid is most appropriate should be based on factors such as pharmacokinetic properties, including bioavailability, route of administration, half-life, neurotoxicity, and the cost of the different drugs. Tramadol and codeine have limitations that may make them less desirable than other opioids in this setting. Tramadol is a prodrug that has limitations in dose titration related to a low threshold for neurotoxicity and has potential interactions with other drugs at the level of cytochrome P450 (CYP) 2D6, 2B6, and 3A4. Codeine is a prodrug, requiring CYP2D6 to allow it to be metabolized to morphine to achieve analgesic effects. (ASCO 2022)|||

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TABLE 2 | (Continued)

|Domain|Recommendation|| |---|---|---| |Pharmacological management (P)|P3|P3 Evidence remains insufficient to recommend any single set of ranges for dose escalation or reduction in opioid titration. Immediate and slow-release oral morphine formulations can be used to titrate the dose. Titration schemes for both types of formulation should be supplemented with immediate release oral opioids, prescribed as required for breakthrough cancer pain. (ESMO)Note: In general, the minimum dose increase is 25-50%, but individual factors such as frailty, comorbidities, and organ function must be evaluated and considered when changing doses. (ASCO 2022)Regular dose of opioid may be increased to incorporate the rescue doses taken in previous 24 h (NCCN), then reassess pain severity and adverse effects within 48 h. (Consensus)Care should be taken when calculating a new regular dose for people who are pain free at rest but have pain on movement (incident pain). If all the analgesia for this pain is incorporated into the new regular morphine dose, such patients could be rendered opioid toxic. In particular, they will be rendered excessively sleepy at rest. This is because pain is a physiological antagonist to the sedative and respiratory depressant side effects of opioids. In such cases, optimum analgesia is achieved by maximizing background analgesia, pre-emptive analgesia for movement-related pain, maximizing nonopioid and adjuvant analgesics, and consideration of other treatment modalities such as radiotherapy, anesthetic nerve blocks, and stabilizing surgery. (NCCN)As organ function deteriorates, drug distribution and clearance change and drug dose was reduced. (Consensus)P4 Methadone should be initiated and titrated only by specialists familiar with its use. (ESMO, NCCN, ASCO 2016, ASCO 2022)ASCO 2016, ASCO 2022)P5 The transdermal route of administration can be considered as an alternative to oral administration if required. Indications for people with cancer include: inability to take oral medications, where lack of access to regular administration of other opioids acts as a barrier to pain management, or patient convenience. Due to the slow onset of effect and long duration of action, the transdermal route should be considered only when pain is stable. There is a reduced risk of constipation with transdermal preparations. (ESMO, NCCN)As organ function deteriorates, drug distribution and clearance change and drug dose will need to be reduced. Use one of the following options, referring to the eviQ Opioid Conversion Calculator:Switch to transdermal buprenorphine (suitable for patients with stable mild pain only). (NICE)Note: A 20 mcg/h buprenorphine transdermal patch is equivalent to 30 mg morphine daily orally.Switch to transdermal fentanyl. (NICE)Note: The lowest dose available (12 mcg/h) for fentanyl transdermal patch is equivalent to 45 mg morphine daily orally.| |Pharmacological management (P)|P6|P6 For people with cancer pain and renal impairment, carefully monitor for treatment-related adverse effects. If opioid-related adverse effects occur, consider the following options:Reduce the total 24-h dose of regular opioid (either by reducing dose and maintaining dose interval or increasing dose interval and maintaining dose). (ESMO)| |Pharmacological management (P)|P7|Switch from sustained release to immediate release opioid at an appropriate regular dosing interval. ASCO (2016, ASCO 2022)Switch to a different opioid (e.g., consider buprenorphine or fentanyl instead of morphine, codeine, or hydromorphone) or methadone under specialist supervision. (ESMO, NCCN)P7 Morphine should be used with caution in people with cancer pain and severe kidney disease(calculated creatinine clearance of less than 30 mL/min) in whom it may require reductions in dose and frequency. (ASCO 2016, ASCO 2022)| |Pharmacological management (P)|P7|Buprenorphine, fentanyl, hydromorphone, methadone, or oxycodone are preferred opioids in severe kidney disease and require careful titration and monitoring. (ASCO 2022) Codeine, a weak opioid often chosen as step 2 on the WHO Cancer Pain Ladder, is metabolized to morphine derivatives within the body and should, therefore, also be avoided when the patient has kidney disease. An alternative weak opioid, Tramadol, can be used with a maximal dose of 50—100 mg bd in patients with a calculated creatinine clearance of 10—30 mL/min or 50 mg bd if creatinine clearance <10 mL/min and undergoing dialysis. Tramadol is dialyzed out, so doses should be given post-dialysis. (Consensus)|

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 TABLE 2 | (Continued)

|Domain|Recommendation Dation ID|Recommendation| |---|---|---| |Pharmacological management (P)|P16|P16 Manage opioid-related respiratory depression according to the severity of symptoms:Withhold the next opioid dose and recommence either at a reduced dose or less frequent dosing interval.Ensure the person is positioned to maintain an airway and provide oxygen if appropriate.If respiratory rate ≤ 8/min and the person is unrouables, use the appropriate dose of naloxone in frequent small doses with the aim to improve consciousness without worsening pain (diluting ampoule to 10 mL). (ESMO, NCCN)If the person is rousable (despite low respiratory rate), monitor them closely for reduced rousability until their respiratory rate improves. Encourage deep breathing.For people receiving fentanyl transdermal patches or methadone, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist, or clinical pharmacologist familiar with the use of the agent. (ASCO 2016, ASCO 2022).P17 Manage opioid-related pruritus (ASCO 2016, ASCO 2022):Rule out other causes (e.g., uremia, cholestasis, medications, or other illnesses).Consider switching to a different opioid.Consider symptomatic management with an H1 antihistamine (choose one of the newer, less sedating agents).P18 Consider switching to a different opioid in either of the following situations:Optimal pain relief cannot be achieved despite appropriate dose. (ESMO, NCCN, NICE)The person is experiencing unacceptable opioid-related adverse effects. (ASCO 2016, ASCO 2022)If the oral route is no longer possible, switch to subcutaneous morphine, hydromorphone, oxycodone, or fentanyl. Transdermal fentanyl is another alternative in stable pain.If switching to a different formulation or route of administration with the same agent, look up conversion for total 24-h opioid dose (ESMO, NCCN, NICE) (e.g., via the eviQ Opioid Conversion Calculator).If switching to a different agent, a starting dose lower than the equivalent total 24-h opioid dose of the previous agent should be used.19 P19 If there is reason to suspect that the person's prescribed opioids are being misused or diverted:Assess for opioid misuse risks before prescribing opioids using one of the following tools: CAGE-AID (the Cut down, Annoyed, Guilty and Eye-opener-Adapted to Include Drugs); SOAPP-R (Screener and Opioid Assessment for Patients with Pain-Revised) or SOAPP-SF (Screener and Opioid Assessment for Patients with Pain-Short Form).The clinician-patient relationship should enable the person to feel safe to self-disclose their current opioid use or opioid use history, or concern for self or family.Clinical suspicion may be raised by any of the list of identified opioid behaviors drawn from the literature including: (i) observable behaviors, for example, not keeping appointments, doctor shopping, requests for scripts via phone, claiming lost or stolen scripts, pill count irregularities, asking for drug by street name, resistance to changes in management plan; (ii) medication noncompliance, for example, self-increasing dose or frequency, self-medicating for nonanalgesic effect including euphoria; (iii) interpersonal behaviors, for example, hoarding drugs, concerns by carers/family, decreased level of functioning; (iv) illegal behaviors, for example, illicit drug use, stealing, selling or forging prescriptions, sourcing drugs illegally. (Ehrentraut et al. 2014)| |Pharmacological management (P)|Urine drug testing may be used to confirm clinical suspicion and/or monitor adherence to treatment. If there is strong suspicion or evidence of opioid misuse, establish a treatment agreement with the person, including an agreement to limit the supply of opioids to a single prescriber and pharmacy. (NCCN)|Unrine drug testing may be used to confirm clinical suspicion and/or monitor adherence to treatment. If there is strong suspicion or evidence of opioid misuse, establish a treatment agreement with the person, including an agreement to limit the supply of opioids to a single prescriber and pharmacy. (NCCN)|

(Continues)

TABLE 2 | (Continued)

|Domain|Recommendation|Recommendation| |---|---|---| |Pharmacological|P20|P20 Advise all patients and carers to ensure medicines are kept out of children's reach at all times, out of sight, and in a secure cupboard. (Consensus)| |management (P)||P21 For patients taking opioids, assess capacity to drive using current national guidelines and warn of impairment at higher doses. (Consensus)| |Pharmacological|P22|P22 If pain is not adequately controlled despite recommended pain management strategies, including analgesic medication, consult a specialist pain medicine physician or palliative medicine physician. (NICE)| |Management (P)||Interventional Pain Management Recommendations (I) What interventional pain management strategies are effective for cancer pain? I1 For people with refractory pain despite carefully titrated doses of conventional pharmacological management and optimal multidisciplinary management, consider interventional options for pain management. These include nerve block and subsequent neurolysis, neuromodulation procedure, or alternative routes of administration of medication such as neuraxial options. Clinicians must take into account pre-existing diagnoses, comorbidities, a full assessment of the type, severity, and prognosis of the pain, and balance potential benefits with the risks of adverse events. (ASCO 2016, ASCO 2022, NCCN)| |Interventional Pain Management (I)|I2|I2 For specific pain syndromes, nerve block and neuromodulation/neurolytic procedures may be considered. Nerve blocks provide minimal duration analgesia and may be employed for diagnostic clarity or to guide the likely efficacy of further intervention. Greater longevity of analgesia is subsequently provided by neuromodulation such as pulsed radiofrequency or neurolysis by chemical or electrical means. Interventional management of pain in pancreatic cancer: Coeliac plexus neurolysis appears to be safe and effective for the reduction of pain in patients with pancreatic cancer, with a significant advantage over standard analgesic therapy until 6 months. Specific interventional considerations between coeliac plexus block and neurolysis and splanchnic radiofrequency should be discussed between local providers. (ESMO) For rectal/perineal pain: Ganglion impar block and neurolysis can be considered. (NCCN)| |Interventional Pain Management (I)|I3|Cordotomy should be available to patients with refractory unilateral pain syndromes. (NCCN) I3 Consider intrathecal infusion of analgesic for patients with any of the following (ESMO, NCCN): difficult-to-control pain—escalating analgesic dose, failure of multimodal therapy, and opioid rotation;| |Cancer-Directed Therapies (C)|C1|diffuse pain; unacceptable opioid-related toxicity despite optimal use of adjuvants and a trial of switching opioids. Refer to a specialist pain medicine physician for delivery and monitoring in conjunction with a palliative medicine physician. (ESMO) Cancer-Directed Therapies (C) What cancer-directed therapies are effective for cancer pain? C1 For people with painful metastases: in bone consider single-fraction radiotherapy or radioisotopes. (ESMO, NCCN) People with recurrent bone pain after previous irradiation should be offered reirradiation with a further dose of 8 Gy. (ESMO) In oligometastatic disease, SBRT should be considered for people who have a good performance status and well-controlled primary sites, preferably within clinical trials. (ESMO) Pharmacogenomic recommendation (PG) Is pharmacogenomic testing recommended prior to cancer pain management? PG1 Pharmacogenetic testing may be considered before initiation of analgesia or if there are concerns regarding toxicity or inadequate analgesic response (NCCN) The current role of pharmacogenetic testing for strong opioids available in Australia remains limited, but with the ongoing advancements in this field and changes to opioid availability, future reassessment is essential.| |Pharmacogenomics (PG)|PG1||

pathways ensures relevance and applicability across diverse health settings. Implementation strategies [21] for the current guidelines include patient pain management plans and goal setting tools which are available on the guideline website [22]; audit of adherence to guideline recommendations and feedback to clinical teams [23]; and health professional education. Dissemination strategies include highlighting the update in peer-reviewed articles [24], conference presentations, social media posts, and on the Cancer Council website. Implementation of specific pathways such as those developed for Cancer Australia for specialist pain management for people with pancreatic cancer which are based on the guideline will also promote dissemination to relevant healthcare professionals. Resources of this kind are becoming more familiar to healthcare professionals through Cancer Australia's promotion of its online Optimal Care Pathways [25] for managing a range of tumors and their impacts on quality of life.

8 | Conclusion

The Cancer Council Australia guideline for managing cancer pain in adults contains recommendations for health professionals of all disciplines to guide appropriate evidence-based care.

Acknowledgments

The guideline update was supported by HammondCare and the University of Melbourne. Cancer Council Australia provided project support to transfer the guideline from the wiki platform to MAGICApp [10].

Funding

The authors have nothing to report.

Conflicts of Interest

There are no conflicts of interest. Clinical pathway reproduced with permission of Cancer Council Australia.

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