Advances in Pharmacologic- and Non-pharmacologic Interventions for Cancer Pain: A Narrative Review.

opinion statementCancer pain is common, heterogeneous, and multidimensional. The management of cancer pain is evolving toward a personalized, mechanism-informed, and multimodal paradigm. In my practice, systematic pain assessment is performed early, and individualized analgesic therapy is initiated promptly rather than deferred until tumor-directed therapy achieves measurable effects. Opioids remain essential but are limited by toxicity, tolerance, and incomplete control of mixed nociceptive-neuropathic mechanisms. Careful agent selection, dose titration, proactive management of constipation and neurotoxicity, and early consideration of opioid rotation are essential to sustain efficacy and safety. Evidence questions routine acetaminophen add-on to strong opioids and supports individualized risk stratification when using nonsteroidal anti-inflammatory drugs (NSAIDs). For neuropathic and treatment-related pain, gabapentinoids and duloxetine remain key adjuvants. Emerging options, including cannabinoids, novel gabapentinoids (mirogabalin and criligabalin), anti-nerve growth factor (NGF) antibodies, and transient receptor potential vanilloid 1 (TRPV1)-targeted therapies (intrathecal resiniferatoxin and high-concentration capsaicin patches), show variable efficacy and require further evaluation before routine use. For refractory pain, neurolytic blocks, intrathecal drug delivery, and neuromodulation may provide meaningful opioid-sparing analgesia in selected patients. These strategies can provide meaningful analgesia and reduce systemic opioid exposure. Nonpharmacologic modalities, including cognitive-behavioral therapy, mindfulness-based interventions, exercise, acupuncture, and transcutaneous electrical nerve stimulation, should be incorporated whenever feasible to reduce symptom burden, improve physical function, and support patient coping and overall well-being. This approach ensures that pharmacologic and nonpharmacologic strategies are applied in an integrated, patient-centered manner. Ultimately, optimal cancer pain management requires coordinated multidisciplinary care, shared decision-making, and ongoing reassessment to align analgesic strategies with disease trajectory, patient goals, and quality of life.