Cancer Pain

The curriculum asks us to describe "the basic assessment and management of cancer pain in adults".

Advanced cancer pain was a new SAQ in March 2018 and had the best pass rate of the paper (85.5%).

In a 2026 CRQ on chronic back pain, candidates dropped marks on the red flags for cancer pain.

Resources

Pain is a common symptom in those with malignant disease
With improving survival, cancer is increasingly a long-term condition; ~50% of those diagnosed today will live for more than 10 years

Moderate-to-severe pain affects ~10 - 40% of cancer survivors

Its aetiology is multifactorial and therefore may be difficult to treat
Each patient requires a personalised, multidisciplinary approach; no two patients or cancers are the same

Pre-existing and unrelated conditions

~10 - 15% of pain in cancer patients is unrelated to the cancer or its treatment, e.g.:

Musculoskeletal conditions, worsened by deconditioning
Chronic primary pain
Headache, pancreatitis, renal colic

Depression (~20%) and anxiety (~10%) are more common in cancer survivors and amplify the perception of pain

Tumour-related

(Mass) effects of the tumour itself

Inflammation
Compression e.g. of nerves
Ischaemia e.g. impinging on vasculature
Oedema e.g. interrupted venous/lymphatic drainage

Tumours secrete chemical mediators (ATP, cytokines, protons, endothelin, neurotrophic factors) which sensitise nociceptors and lower their firing threshold

Cancer-induced bone pain: from primary bone malignancy or metastases; has both inflammatory and neuropathic components

↑ RANK-ligand expression drives ↑ osteoclast activity, disrupting bone homeostasis
Nerve growth factor stimulates formation of abnormal periosteal microneuromas, which are further sensitised by tumour inflammatory mediators

Paraneoplastic phenomena

Production of anti-Hu and anti-Yo neuronal antibodies causes peripheral neuropathy/neuritis

Central sensitisation

Treatment-related

Surgery: chronic post-surgical pain, especially after breast, thoracic and amputation surgery

Radiotherapy (used in ~50% of cancer patients)

Causes inflammation, oxidative stress (reactive oxygen species) and pro-inflammatory cytokine release (IL-1, TNF-α)
Radiation fibrosis syndrome may be acute (days to weeks) or chronic (months to years)
Radiation-induced peripheral neuropathy is progressive and irreversible and may present years later

Acute radiotherapy-related pain	Late radiotherapy-related pain
Oral mucositis	Radiation fibrosis syndrome e.g. muscle spasm, lymphoedema
Oesophagitis	Osteoradionecrosis of the jaw
Enteritis and proctitis	Oesophageal and lower GI tract strictures
Dermatitis	Peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN)

Length-dependent sensory neuropathy in a glove and stocking distribution, with both loss (paraesthesia) and gain (allodynia, hypersensitivity) of function
Incidence ~60% at 3 months and ~30% at 6 months
Causative agents: vinca alkaloids (vincristine), platinum compounds (cisplatin, oxaliplatin) and taxanes (paclitaxel, docetaxel)
Risk factors: pre-existing neuropathy, diabetes, renal failure, smoking

Immunotherapy

Abdominal pain, colitis, pancreatitis, arthralgia, myalgia and neuropathic pain
Immune checkpoint inhibitors cause rheumatological reactions (e.g. inflammatory arthritis, myositis, vasculitis) in up to 10%

Hormonal therapy

Aromatase inhibitors (breast cancer) cause a polyarthralgia of the hands, wrists and knees in ~50% of patients, which may affect compliance

Associated conditions

Hypercalcaemia e.g. from parathyroid hormone-related peptide
Osteoporosis ± pathological fractures
Prolonged immobility and pressure sores
Immunosuppression: skin abscesses, infection of damaged tissue, herpes zoster reactivation

Pain in cancer has physical, psychological, social and spiritual components and should be assessed within a biopsychosocial framework
Establish the likely mechanism(s): nociceptive (somatic/visceral), neuropathic or mixed, as this guides treatment
Always consider non-oncological causes

Red flags

Features suggesting spinal malignancy or metastatic spinal cord compression should prompt urgent investigation:

Past history of cancer
Unexplained weight loss
Thoracic pain
Progressive, severe or nocturnal pain
New neurological deficit or sphincter disturbance

General principles

Multidisciplinary team input: pain and palliative care specialists, oncologists, specialist nurses and allied health professionals
Prehabilitation before painful treatments (e.g. major surgery) reduces post-operative pain and improves function

A full programme may not be feasible given the time-critical nature of cancer surgery, but physiotherapy and psychology input should ideally occur beforehand

Psychological and physical

Grief counselling
Cognitive behavioural therapy
Relaxation techniques
Pain management programmes
Physiotherapy and massage therapy
Hypnotherapy and music therapy

Complementary therapies

Acupuncture: releases opioid peptides and serotonin; more effective combined with drug therapy than drug therapy alone
TENS: evidence is conflicting, but it is cheap and low-risk so is worth considering as part of a multimodal strategy
Reflexology
Herbal remedies
Reiki

WHO analgesic ladder

Stepwise escalation from paracetamol/NSAID ± adjuncts to strong opioids ± adjuncts; strong opioids may be needed earlier

Has several limitations:

Most effective for acute nociceptive cancer pain but less suited to the chronic pain seen in survivors
Built around opioid escalation and not designed for neuropathic pain e.g. gabapentinoids and SNRIs are not included
Best viewed as a starting point for the non-specialist rather than a definitive approach

ESMO recommendations

Pain	Recommendation
Mild	WHO ladder: paracetamol and/or NSAIDs
Moderate	Weak opioid plus non-opioid, or low-dose strong opioid
Severe	Oral morphine first-line; fentanyl/buprenorphine safest if eGFR <30; SC route if others fails; IV for rapid control
Breakthrough	Immediate-release opioids
Bone	External beam radiotherapy (8Gy single dose); denosumab
Neuropathic	Gabapentinoid, tricyclic or duloxetine

Opioids

Opioids are, in general, very effective, particularly for acute nociceptive pain
Start at the lowest possible dose, initially as an immediate-release preparation, before converting to long-acting opioids

The dose is up-titrated e.g. by 30 - 50% over a few days until symptom control is achieved
Breakthrough pain can be managed with shorter-acting variants e.g. PRN oral morphine dose at 1/6th total daily morphine dose

Morphine doses >90mg associated with increased side effects without additional benefit

Patients on high doses (e.g. >60mg morphine/24hrs) may benefit from fentanyl patches

In patients with a low eGFR, oxycodone (<30ml/min) or alfentanil CSCI (<20ml/min) are used instead

Problems with opioids

Side-effects e.g. constipation, nausea, sedation
Less appropriate for long-term use in survivors due to addiction potential and opioid-induced hyperalgesia
Opioid-induced hyperalgesia can cause a paradoxical increase in pain

Reduction in opioid dose should be the first action in this case
Administration of alternative analgesics and pharmacotherapy for side-effects should follow
Opioid rotation to oxycodone may be necessary

Retrospective data suggest opioids may worsen cancer survival (?TLR4 interaction) although this is controversial and must be balanced against the pro-oncogenic effects of untreated pain itself

Antineuropathic agents

Neuropathic pain affects 15 - 44% of cancer patients
Gabapentinoids, tricyclic antidepressants and SNRIs; duloxetine has the most robust evidence
Topical agents, mostly used for CIPN:

Menthol: TRPM8 agonist
Capsaicin: TRPV1 agonist; depletes substance P and desensitises the receptor
Local anaesthetics e.g. lidocaine patches, EMLA
Doxepin: a topical tricyclic

Other adjuncts

NSAIDs: generally well tolerated in palliative care
NMDA antagonists e.g. ketamine, methadone
Anti-spasmodics e.g. hyoscine
Steroids to reduce local mass effects
Cannabinoids (not licensed in the UK): no conclusive benefit in cancer pain, and may worsen outcomes in patients receiving immunotherapy
Bisphosphonates for bone pain due to metastases or osteoporosis

Do not target solitary metastases and may be more appropriate when there is scattered pain
Only modest pain reductions; less effective than radiotherapy
Poor PO bioavailability and should be given as IV infusion
Best evidence is in bony metastases from breast cancer, multiple myeloma and prostate cancer

Denosumab (RANK-ligand inhibitor) for bone pain

Oncological

Chemotherapy
Radiotherapy

Localised external beam radiotherapy (e.g. 8 Gy single dose) to target individual metastases, especially if opioid-refractory

Initial flare in pain from skin reaction to radiotherapy for 7 - 10 days
Subsequent reduction in pain as bony sclerosis occurs over 4 - 6 weeks
80% of patients respond

Wide field radiotherapy can be efficacious for localised bone pain, with response in 60% of patients (NNT 3.6)

Hormonal therapy e.g. tamoxifen
Immunotherapy e.g. trastuzumab (Herceptin)
Radio-isotope treatment for multiple bony metastases e.g. IV strontium-89 is as efficacious as wide field radiotherapy but with fewer side effects

Surgical

Curative surgery
CSF shunt procedures
Management of pathological fractures, but no benefit to fixation without fracture
Management of bowel obstruction

Interventions are usually reserved for pain refractory to conventional management
Patients with cancer may be at higher risk of complications (e.g. immunosuppression, coagulopathy) and may have limited life expectancy, so risks and benefits must be weighed carefully

Botulinum toxin

Prevents ACh release at the neuromuscular junction: useful in musculoskeletal pain
Inhibits neurotransmitter and inflammatory mediator release from sensory nerves: useful in localised neuropathic pain

Neuromodulation

Peripheral nerve stimulation: implanted electrodes targeting discrete nerves; may be used in CIPN though evidence is limited
Spinal cord stimulation: epidural electrodes; recommended for neuropathic pain in the UK but limited evidence specific to cancer pain
Intrathecal drug delivery via an externalised or implanted pump

Opioids act directly on central μ receptors, avoiding peripherally mediated side-effects; oral:intrathecal morphine ratio is ~300:1
Allows use of drugs only effective intrathecally e.g. ziconotide (N-type calcium channel blocker derived from cone snail toxin), which does not cause tolerance and can be stopped abruptly

Advantages	Disadvantages
Much smaller opioid doses required	Resource intensive; only available in specialist centres
Fewer systemic side-effects	Procedural risks e.g. infection, bleeding
Allows delivery of novel drugs e.g. ziconotide	Ongoing pump refills and maintenance

Neuroablative procedures

Mainly used in the terminal phase, where the risk/benefit balance favours more invasive options
One can target neural pathways at different levels:

Central e.g. IT neurolysis, neuraxial infusions, cervical cordotomy (should be available for refractory cases)
Visceral (autonomic nervous system) e.g. coeliac plexus block (indicated in pancreatic cancer), superior hypogastric block, ganglion impar block
Peripheral (somatic) e.g. radiofrequency ablation or pulsed radiofrequency, nerve block using phenol

Cancer pain care is often fragmented between primary, secondary and tertiary services with poor communication
The Faculty of Pain Medicine framework (2018) recommends specialist cancer pain services which integrate with primary and secondary care

Provides a referral route for complex patients to access advanced therapies such as intrathecal drug delivery and cordotomy

Key themes: multidisciplinary working, effective communication and personalised care