Narrative review of pharmacologic and interventional strategies for cancer pain management in adults with incurable disease.

Abstract

Background and objective: Cancer pain affects 55-95% of patients with advanced malignancy and remains inadequately controlled in approximately two-thirds of those with metastatic disease. Management is shifting toward a multimodal, mechanism-based and personalised approach. This narrative review summarises current evidence and international guideline recommendations on cancer pain management in adults, with a clinical focus on incurable disease.

Methods: PubMed/MEDLINE, Embase and the Cochrane Database of Systematic Reviews were searched from 1 January 2000 to 30 April 2026, supplemented by handsearching of international oncology, palliative-care and pain-medicine guidelines and of the 2025 multi-society consensus on opioid conversion. Systematic reviews, meta-analyses, randomised trials and current guidelines were prioritised.

Key content and findings: Opioids are indicated for moderate-to-severe pain caused by cancer or its treatment and in palliative care; this indication should not be extrapolated to chronic non-cancer pain, where their benefit is small and comparable to non-opioid alternatives. The distinction is mechanistic: µ-opioid receptor agonism damps transmission from intact, continuously driven nociceptors, whereas nerve injury dismantles part of that target, so that antidepressants and anticonvulsants-not opioids-are first-line for neuropathic pain; methadone, buprenorphine, tapentadol and tramadol are partial exceptions owing to their additional non-opioid mechanisms. Titration and rotation remain central, with conversion ratios used as a starting framework rather than a fixed rule. Methadone, including intravenously, is valuable in neuropathic and opioid-refractory pain under specialist oversight. Rapid-onset transmucosal fentanyl outperforms oral morphine for breakthrough pain. Evidence does not support routine use of cannabinoids. Intrathecal drug delivery benefits carefully selected refractory patients, but the limitations of the published literature highlight the risk of premature procedural escalation before systemic optimisation. Non-pharmacologic interventions, palliative radiotherapy and pharmacogenomic-guided prescribing complete the framework.

Conclusions: Effective cancer pain management combines mechanism-based pharmacotherapy with evidence-informed interventional strategies and psychosocial support. Methadone, intrathecal therapy and emerging biased agonists each have a defined place, but none replaces clinical judgement and prior optimisation of systemic therapy. Restrictive frameworks developed for chronic non-cancer pain should not be applied to incurable cancer, where under-treatment remains the dominant risk; conversely, opioid efficacy in cancer pain does not endorse their use in non-cancer, particularly neuropathic, pain.