Cancer survivors and cancer pain

Learning objectives.

By reading this article you should be able to:

• •Describe the mechanisms of cancer treatments and how these may relate to pain in survivors.
• •Explain the causes of acute and chronic pain in patients with cancer.
• •Recall the current and potential future treatment options available for pain in cancer survivors.
• •Discuss how the available advanced interventional cancer pain treatments fit into an interdisciplinary pain strategy.

Key points.

• •Cancer pain is highly complex and each patient will require a personalised approach to their management.
• •The number of cancer survivors continues to increase because of advances in cancer care
• •Whilst the progress in novel therapeutics and advanced interventional techniques for pain is exciting, effective interdisciplinary working remains the key to effective cancer pain management.

Cancer is a significant cause of morbidity and mortality globally. In the UK a diagnosis of cancer is made every 2 min, with an annual incidence of ∼375,000 cases.¹ ‘Cancer survivor’ is a widely used term but is one with a somewhat fluid definition. The most commonly accepted definition is ‘anyone who has ever been diagnosed with cancer no matter where they are in the course of their disease’.² In clinical practice, the more pragmatic definition of ‘those who have finished primary treatment and are living with or beyond the disease’ may be used. For the purpose of this paper we have adopted this definition.

Since 1990, the incidence of cancer in the UK has increased by 12% and it is projected that by 2038 there will be 506,000 cases of cancer per year.¹ Medical advances have transformed cancer care, with 10-yr survival doubling in the last 40 yrs. Approximately 50% of those diagnosed with cancer today will live longer than a decade, meaning that cancer often now represents a long-term condition.³

Improvement in cancer survival has been achieved for several reasons, including earlier detection, advances in radiation oncology, surgical techniques and the introduction of novel, personalised systemic anticancer therapy (SACT) treatment models. This situation, whilst undoubtedly positive, presents new challenges, one being pain. Moderate-to-severe pain is experienced by ∼10–40% of cancer survivors, affecting their function and reducing quality of life.^4,5

Survivors of leukaemia, lymphoma, lung, breast and colorectal cancer generally experience more pain than survivors of other cancers.⁵ Age also appears to be a factor, with those aged >65 yrs at diagnosis less likely to report pain than those aged <65 yrs. Other environmental factors associated with more intense pain include cigarette smoking and insomnia.⁵

Genetic risk factors for cancer can now be identified using DNA sequencing, enhanced surveillance instigated and preventative measures undertaken, for example performing a risk-reduction mastectomy in females carrying a pathogenic mutation in the BRCA1/2 genes.

Multiomic analyses of cancer cells have demonstrated cancer is not a homogenous disease, rather a collection of multiple cancer subtypes, with differential response to treatment. This has led to individually tailored SACT that uses targeted therapy and immunotherapy to exploit genotypic or phenotypic susceptibilities in an individual's cancer. The heterogenous nature of cancer contributes to the challenge in managing pain. No two patients are the same, and no two cancers will have the same genetic makeup, leading to differential responses to treatment and mandating an individualised approach. The growing number of cancer survivors, individuals often experiencing pain, will present a significant challenge to the specialty of pain medicine over the coming decades.

Causes of pain in cancer survivors

Patients with cancer are diagnosed with a life-changing condition and then rapidly treated with a combination of aggressive surgical, radiotherapeutic and chemotherapeutic interventions, often on a background of concurrent complex psychosocial needs. Anxiety, depression, emotional distress and uncertainty are common in cancer survivors and these psychological factors all have potential to enhance pain. The causes of pain in cancer survivors are therefore broad and multidimensional.

Oncological treatment, whilst improving survival, may also have harmful physical and psychological effects. Patients are therefore at risk of developing disease-related pain, but also treatment-related pain and pain caused by associated conditions. Frequently, cancer survivors have significant comorbidity and are therefore susceptible to a range of non-cancer-related pain syndromes. The causes of pain in cancer survivors are summarised in Figure 1.

Fig 1.

Causes of pain in cancer survivors.

Tumour-related pain

Tumours are metabolically active and secrete numerous chemicals including ATP, cytokines, protons, endothelin and neurotrophic factors which sensitise nociceptors.⁶ These chemical mediators induce and upregulate proteins that control nociceptor excitability at transcriptional or post-translational level, thereby decreasing nociceptor firing threshold.⁷ Tumours may also cause mechanical compression of surrounding structures, including nerves and organs, to produce a variety of neuropathic, nociceptive and visceral pain syndromes.

Cancer-induced bone pain (CIBP) represents a discrete pathological condition that has elements of both neuropathic and inflammatory pain, and encompasses pain caused by either primary bone malignancy or secondary bone metastases.⁸ Normal bone homeostasis is disrupted by increased osteoclast activity in cancer states driven by the amplified expression of the receptor activator of nuclear factor kappa-B (RANK)-ligand.⁸ Increased formation of abnormal periosteal microneuromas, stimulated by nerve growth factor (NGF) secretion also occurs.^8,9 These neuronal fibres are further sensitised by the release of inflammatory mediators by tumour cells.⁹ The combination of these factors commonly leads to severe pain that is challenging to manage.

Treatment-related pain

The treatment approaches adopted for specific tumour types vary, but can broadly be categorised as surgery, radiotherapy/nuclear medicine and SACT. These treatments are commonly delivered in combination and may all generate pain.

Surgery-related pain

Surgical management can lead to a range of acute and chronic pain syndromes. Chronic post-surgical pain syndrome is defined as ‘pain that started or worsened post-surgery, at the site of surgery or the innervation of involved nerves, that lasts for longer than 3 months’.¹⁰ Its incidence depends on a number of risk factors and site of surgery, with breast, thoracic and limb amputation surgery being particularly high risk. It often has neuropathic features including hyperalgesia, allodynia and dysaesthesia.¹⁰

Radiotherapy-related pain

Radiotherapy is used in ∼50% of patients with cancer. The incidence of radiotherapy adverse effects has decreased as a result of improvements in the precision of treatment. However, it can still cause significant morbidity.

Radiotherapy induces tissue damage via inflammation, oxidative stress and by triggering an innate immune response. Ionising radiation causes direct cell injury and induces reactive oxygen species that produce further oxidative damage.⁶ The radiation can also alter gene expression, which can lead to the release of proinflammatory cytokines such as interleukin-1 and tumour necrosis factor-α, triggering inflammation and nociceptor sensitisation.⁶

A range of painful conditions may arise after radiotherapy; the proinflammatory state induced in healthy tissue can lead to fibrosis. This can present as acute radiation fibrosis syndrome (ARFS)—manifesting within days to weeks of treatment or as chronic radiation fibrosis syndrome (CRFS)—which develops months to years after treatment radiation fibrosis syndrome can cause chronic pain, through multiple mechanisms such as dermatitis, ulceration, muscle contractures, mucositis and direct neuronal fibrosis (Table 1).⁶

Table 1.

Examples of radiotherapy-induced pain syndromes and associated symptoms.

Acute phase radiation-related pain	Symptoms	Late phase radiation-related pain	Symptoms
Enteritis	Abdominal pain Diarrhoea Vomiting	Radiation fibrosis syndrome	Dependent on area affected -dystonia -muscle spasm -lymphoedema
Oesophagitis	Dysphagia Vomiting Reflux Cough	Osteoradionecrosis of jaw	Pain Trismus Orocutaneous fistula Non-healing ulcers
Oral mucositis	Oral Pain Ulcers Dysgeusia Weight loss (secondary decreased oral intake)	Oesophageal stricture	Reflux Bitter/acid taste Hiccups Dysphagia Weight loss
Proctitis	Tenesmus Pus/blood in stool Diarrhoea Abdominal pain	Dyspareunia	Painful intercourse
Dermatitis	Colour changes Swelling Desquamation/skin breakdown	Lower GI tract stricture	Painful defaecation (anal stricture) Bowel obstruction
		Peripheral neuropathy	Gain or loss of function neuropathic symptoms

Radiation-induced peripheral neuropathy is a progressive and irreversible peripheral neuropathy that can present years after treatment cessation. Radiotherapy can cause direct axonal injury and demyelination, and injury to vasculature and consequently ischaemic damage. This, when coupled with the fibrosis observed with CRFS leads to a chronic peripheral neuropathy.

SACT-related pain: chemotherapy

Chemotherapy is effective at destroying malignant cells, but also causes cellular death in healthy tissues. Chemotherapy may cause a range of unpleasant symptoms including hair loss, nausea and fatigue, which may contribute to the development of psychological morbidity; these in turn can worsen any pain state that may have developed.

A number of agents can cause chemotherapy-induced peripheral neuropathy (CIPN). Chemotherapy-induced peripheral neuropathy presents as a length-dependent sensory neuropathy, typically in a glove and stocking distribution with some fine motor and balance effects because of abnormal proprioception. It can have both loss of function (paraesthesia, dysaesthesia) and gain of function (hypersensitivity, allodynia) symptoms. The incidence of CIPN varies depending on the drug, but is ∼60% at 3 months after treatment and 30% at 6 months.¹¹ There are a number of identified risk factors (pre-existing neuropathy, smoking, renal failure, diabetes) and underlying genetic risk. Agents commonly associated with CIPN include vinca alkaloids (vincristine), platinum compounds (cisplatin and oxaliplatin) and taxanes (paclitaxel and docetaxel). The cause of CIPN is thought to be multifactorial, representing a combination of mitochondrial toxicity, proteosome inhibition, anti-angiogenesis and microtubule disruption.¹²

SACT-related pain: immunotherapy

Immunotherapy has arguably made the largest contribution to the recent improvements in cancer survival rates. The main modalities include:

• (i)Monoclonal antibodies: synthetic antibodies that target specific antigens.
• (ii)Immune checkpoint inhibitors: these block surface proteins primarily expressed on immune cells that partially restore anticancer immune mechanisms.
• (iii)Adoptive T-cell therapy: genetically trained host T cells against cancer cells.
• (iv)Immune system modulators: these destroy cancer cells by increasing circulating cytokines or minimise the effects of cancer treatment.

Immunotherapy can cause a wide range of pain symptoms, including abdominal pain, arthralgia and myalgia, arthritis, colitis, pancreatitis, dermatological blisters/sores and neuropathic pain. Immune checkpoint inhibitors are particularly implicated in the development of rheumatological adverse reactions in up to 10% of patients.¹³ These rheumatological complications include arthralgia, inflammatory myositis, systemic lupus erythematosus (SLE)/Sicca syndrome, sarcoidosis and vasculitis with associated neuropathy. The intensity of these reactions can be mild, responding to simple analgesics, but can also be severe, requiring the of cessation of treatment and initiation of immunosuppression.¹³

SACT-related pain: adjunctive treatment

Whilst many non-chemotherapeutic SACTs have favourable tolerability characteristics, there are a few exceptions.

Aromatase inhibitors (AIs) are drugs used to treat and prevent recurrence of oestrogen receptor-positive breast cancer. They work by inhibiting the enzyme aromatase which converts androgens into oestrogens. Their use may result in the development of aromatase inhibitor-associated arthralgia which is a polyarthralgia affecting mainly the wrists, hands and knees.¹⁴ It affects around 50% of those taking AIs and may have an impact on treatment compliance in 20% of those affected.¹⁴ The aetiology of this condition remains poorly understood, but it is believed to be related to oestrogen depletion, with cytokine release and vitamin D deficiency contributing.

Pain from associated non-oncological conditions

Cancer survivors have a severe systemic disease, are treated aggressively for years and are susceptible to a range of painful secondary conditions. Survivors are often physically deconditioned and may experience weight loss and have prolonged immobility placing them at risk of pressure-related skin damage—a painful and therapeutically challenging situation. Prolonged immobility, SACT adverse effects and nutritional deficiency can also lead to osteoporosis and osteoporotic fractures. In certain cancers, hypercalcaemia can be a problem as a result of activity of parathyroid hormone-related peptides, which may lead to pain and emotional instability amongst other symptoms. Patients are often immunosuppressed which can lead to painful primary infections (such as skin abscesses), secondary infection of damaged tissue (as a result of radiotherapy or surgery) and reactivation of previous infection (herpes zoster).

Pain unrelated to cancer

Cancer survivors also experience painful conditions that affect the non-cancer population. Around 10–15% of pain in cancer patients is unrelated to the cancer or its treatment.¹⁵ Cancer survivors have a higher prevalence of mental health conditions than the general population (depression 20%, anxiety 10%) which alters and amplifies the perception of pain. Pre-existing musculoskeletal conditions are also exacerbated by the significant deconditioning that may occur as a result of disease or treatment.¹⁶ When assessing pain in cancer survivors it is therefore important to also consider non-oncological causes.

Management

Pain, particularly pain encountered in patients with cancer, extends beyond purely physical sensations, and involves social, emotional and spiritual elements. The role of a multidisciplinary team, including allied health professions, pain and palliative care specialists, oncologists and specialist nurses is important. Patients should be treated holistically as individuals with the majority of cancer pain being treated with a multimodal, multidisciplinary approach. A range of non-pharmacological adjunctive strategies have been shown to be effective in patients with cancer including, massage therapy, physiotherapy, hypnotherapy and music therapy.¹⁷

The European Society for Medical Oncology (ESMO) has made recommendations for the pharmacological management of cancer pain, which are summarised in Table 2.¹⁹ Cancer is a heterogenous disease where the same condition can be genetically and phenotypically different in different patients. Patients with cancer are therefore individuals who do not follow algorithms, and whilst guidelines provide a useful starting point they are neither definitive nor universal.

Table 2.

Summary of ESMO clinical practice guidelines.¹⁸ eGFR, estimated glomerular filtration rate; TD, transdermal.

Condition	Recommendation	Level of recommendation
Mild pain	WHO ladder Paracetamol—no evidence to support or refute NSAID—no evidence to support or refute	II, B I, C I, C
Moderate pain	Weak opioids in combination with non-opioids Low-dose strong opioids is alternative	III, C II, C
Severe pain	Oral morphine first line Fentanyl/buprenorphine safest in eGFR <30 Subcutaneous route considered if failed p.o. or TD I.V. infusion only considered when s.c. contraindicated For rapid pain control use i.v. opioid	I, A III, B III, B III, B III, B
Breakthrough pain	Immediate-release opioids	I, A
Bone pain	External beam radiotherapy (8 Gy single dose) Denosumab	I, A III, A
Neuropathic pain	First line: gabapentinoid, tricyclic or duloxetine Interventional treatments have inconclusive evidence	I, A II, C
Interventions	Cordotomy should be available in refractory cases Coeliac plexus block indicated in pancreatic cancer	V, C II, B

Pre-emptive treatment

Prehabilitation and risk stratification are important strategies to try and reduce the risk of chronic pain developing and can be used before any potentially painful treatment.

Prehabilitation is the process of optimising physical and psychological health before an invasive treatment such as major surgery. It has been demonstrated to decrease postoperative pain and increase functional levels.²⁰ A full prehabilitation programme may not always be feasible in cancer patients because of the time-critical nature of surgery, but physiotherapy and psychology input should ideally occur before cancer treatment.

Pharmaceutical approaches

In 1986, in response to the recognition that cancer pain is commonly poorly controlled, the World Health Organization (WHO) proposed the first WHO pain ladder which has since been updated, but remains largely unchanged.²¹ It advocates a stepwise progression in treatment from paracetamol/NSAID with or without adjuncts at the base to strong opioids with or without adjuncts.

The guidelines are most effective at treating acute nociceptive cancer pain. However, with the changing nature of cancer pain from an acute to more chronic condition, the ladder may not represent the optimal approach in all patients.

The WHO guidelines are based around opioid escalation (both strength and dose), and are not written specifically for neuropathic pain. Antineuropathic agents are recommended in the updated WHO guidelines, but as adjunctive therapies with limited guidance on how or when they should be used.²¹ The ladder also does not include gabapentinoids and serotonin noradrenaline reuptake inhibitors (SNRIs), which have a role in the treatment of neuropathic pain. Rigid adherence to the WHO guidelines when treating cancer pain with neuropathic features could lead to suboptimal management. The WHO guidelines should therefore be viewed as a good starting suggestion for the non-specialist managing cancer pain, rather than the definitive approach.

Topical agents

A number of topical agents are available for the treatment of neuropathic pain. In cancer survivors, they are most commonly used for the treatment of CIPN. Menthol cream acts on the transient receptor potential melastatin 8 (TRPM8), which is upregulated in neuropathic pain and the use of menthol cream can reduce neuropathic symptoms.²² Local anaesthetics can be delivered topically either via patches or cream (EMLA/AMETOP) and although randomised controlled trial evidence supporting use is limited, it has been shown to be effective in individual studies.²³ Capsaicin is an agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1). It depletes neuronal substance P and therefore desensitises the TRPV1 receptors resulting in analgesia. Topical capsaicin via cream or patch is effective in reducing neuropathic pain.²⁴ Doxepin is a tricyclic antidepressant that can be delivered topically and can reduce the intensity of CIPN.²⁵

Opioids

Opioids remain an important component of analgesic treatment for cancer pain in most patients and are particularly effective for acute nociceptive pain. However, opioids are less appropriate for the chronic pain often seen in survivors of cancer because of their adverse effects, including the potential for addiction, and the development of opioid-induced hyperalgesia syndrome.

Whilst being potent analgesics, they may pose specific issues in cancer patients. Limited retrospective evidence suggests that opioid use may lead to worsening cancer survival outcomes.²⁶ However prospective evidence is currently lacking and this remains controversial. The mechanisms for this potential association were initially thought to be the immunological and proangiogenic properties of opioids, but more recently it has been proposed that an interaction with TLR4 receptors may be responsible.

Despite this, contradictory evidence demonstrates that opioids can be used safely in cancer survivors when monitored appropriately.²⁷ Using the lowest possible dose, initially in an immediate-release preparation, is supported by recent guidelines.¹⁸ The potential concerns around opioids should be weighed against the potential pro-oncogenic properties of pain itself, related to adrenergic effects on cancer cells.²⁸ Effective pain management therefore remains a priority, and a pragmatic multimodal approach to pain management, including the use of opioids, represents current best practice.

Non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs are effective non-opioid drugs for a variety of acute and chronic pain syndromes. Because of adverse effects they are not always appropriate for long-term use, but recent data suggest they are tolerated well in (mainly oncological) palliative care and remain an important drug class to consider.²⁹

Antineuropathic agents

Neuropathic pain is common and affects between 15% and 44% of cancer patients.³⁰ The International Association for the Study of Pain (IASP), ESMO and WHO have each assessed the evidence for different drugs for neuropathic pain, and their findings are summarised in Table 3, Table 4, Table 5.^19,21,31 A recent Cochrane review of antidepressants for non-cancer neuropathic pain demonstrated that the use of duloxetine was supported by the most robust evidence.³²

Table 3.

IASP NeupSIG recommendations for the management of neuropathic pain in adults.³¹ NMDA, N-methyl-d-aspartate; SSRI, selective serotonin reuptake inhibitor; TCAD, tricyclic antidepressant drugs.

Recommended	Inconclusive evidence	Weak against	Strong against
TCADs SNRIs Pregabalin Gabapentin Lidocaine patch Capsaicin patch Tramadol Botulin toxin A	Capsaicin cream Carbamazepine Topical clonidine Lamotrigine NMDA antagonists Oxycarbazepine SSRI antidepressants Tapentadol Topiramate Zonisamide	Cannabinoids Sodium valproate	Levetiracetam Mexiletine

Table 4.

Summary of WHO recommendations regarding medication for neuropathic pain in cancer.³⁰ TCAD, tricyclic antidepressant drugs.

Recommended	No recommendation for or against	Recommended against
Nil	TCADs SRNIs Gabapentin Pregabalin Carbamazepine Sodium valproate	Nil

Table 5.

Summary of ESMO cancer pain guidelines regarding medication for neuropathic cancer pain.¹⁸ TCAD, tricyclic antidepressant drugs.

Recommended	No recommendation for or against	Recommended against
TCAD		Ketamine
Gabapentin		Levetiracetam
Pregabalin		Mexiletine
Duloxetine
Opioids

Cannabinoids

There is some interest regarding the use of cannabinoids or agents acting on the endocannabinoid system for the management of pain and other symptoms including emesis, anorexia and insomnia. As the field matures, there is developing evidence for using cannabinoid in non-cancer chronic pain. However, despite animal model studies demonstrating benefit of cannabinoids in CIPN, a recent meta-analysis specifically focussing on cannabinoids in cancer pain did not show conclusive benefit.³³ Furthermore, because of the immunomodulatory effects of cannabinoids, there is some evidence of negative survival outcomes in patients receiving immunotherapy.³⁴ This is an area in which further research in line with the IASP recommendations is undoubtedly required.

Interventional approaches: botulinum toxin

Botulinum toxin is being increasingly used in chronic pain, where it has a dual mechanism of action. At the neuromuscular junction it works to prevent the release of acetylcholine and can therefore be useful in pain of musculoskeletal origin. It also has an action on sensory nerves whereby it inhibits the release of neurotransmitters and inflammatory agents and is therefore useful in localised neuropathic pain, with clinical evidence demonstrating both efficacy and safety.³⁵

Interventional approaches: neuromodulation

Neuromodulation is the process by which nerve function can be altered by the direct application of electricity or biochemicals to neurones.

Acupuncture

Medical acupuncture may be used as an initial neuromodulatory therapy. Acupuncture is thought to work by mediating the release of opioid peptides, serotonin and other local and systemic signalling molecules. A systematic review has demonstrated acupuncture plus drug therapy is more effective than conventional drug therapy alone for cancer-related pain and its use in an integrated fashion in cancer pain is recommended by the American Society of Clinical Oncology.^36,37

Transcutaneous electrical nerve stimulation

Transcutaneous electrical nerve stimulation (TENS) is a noninvasive neuromodulation technique that involves placing small skin electrodes over peripheral nerves or the spinal cord. Evidence supporting TENS in cancer pain is contradictory. A Cochrane review found insufficient evidence to support its routine use. However, more evidence has since been published. In one study TENS was effective in 70% of patients with cancer pain.^38,39 As it has a favourable risk–benefit profile, and is low cost, TENS should be considered as part of a multimodal analgesic strategy.

Peripheral nerve stimulation

Where pain is limited to discrete locations or dermatomes, specific nerves can be targeted using stimulators implanted percutaneously under image guidance. Nerves can then be directly stimulated providing analgesia to the innervated area. It is an emerging analgesic therapy for chronic pain. It has been shown that potentially two-thirds of patients with chronic neuropathic pain will gain >50% pain relief with peripheral nerve stimulation.⁴⁰ With regards to pain in cancer survivors, peripheral nerve stimulation may be used in CIPN, but data on efficacy are limited.

Central neuromodulation: spinal cord stimulation

Pain signals can be modulated centrally, either via deep brain stimulation (DBS) or spinal cord stimulation (SCS). Central neuromodulation is resource intensive and has risks. However, it can be effective in managing refractory pain. Patients with cancer may be at increased risk of complications because of the effects of disease or treatment, and may have limited life expectancy. All factors need to be carefully considered before implantation.

Spinal cord stimulation involves placing electrodes into the epidural space either percutaneously or surgically. Its mechanism was initially felt to be related to the gate control theory of pain, whereby stimulation of A-β fibres prevents transmission of nociceptive input from A-δ and C fibres. However, it is now known to be more complex with a range of neurochemical and sympathetic changes observed.⁴¹ In the UK, SCS is recommended for use in neuropathic pain but there is limited specific evidence supporting use in cancer pain.⁴²

Chemical neuromodulation: intrathecal drug delivery

Systemic opioids deliver most of their therapeutic effect via central μ opioid receptors. The adverse effects are predominantly mediated by peripheral receptors that convey little or no benefit in terms of analgesia. The intrathecal delivery of opioids is therefore an attractive option. Much smaller doses of drug can be introduced (oral:intrathecal=300:1) directly to the site of action, maximising analgesia whilst minimising adverse effects. Intrathecal opioids can be delivered in a single shot (e.g. as adjunct to acute pain from surgery) or via an intrathecal catheter, and either an externalised or implanted pump for longer term use.

Intrathecal catheters also facilitate the delivery of novel drugs that are unavailable via other routes, because of adverse effects or lack of efficacy. For example, ziconotide, a drug derived from cone snail toxin, is an N-type voltage-gated calcium channel blocker that must be delivered intrathecally.⁴³ It can be effective for neuropathic pain and, although unlicensed, can be combined with opioids within intrathecal delivery systems. A particularly favourable property is that unlike opioids, prolonged use does not lead to tolerance, and it can be stopped abruptly without issue.

Interventional approaches: ablative procedures

Neuroablative procedures such as nerve blocks, thalamotomy and cordotomy are effective in the management of cancer pain. However, these specialised interventions are predominantly deployed in the terminal phase of cancer where the balance of risks and benefits is altered and the potential adverse effects more acceptable. As this review focuses on cancer survivors, these procedures are not discussed.

Non-clinical considerations in cancer pain

Organisation

The management of cancer pain is often disjointed and shared between numerous services located both in primary and secondary or tertiary care, a situation characterised by poor communication and limited integration. A framework for service improvement was developed in response to evidence of suboptimal treatment of cancer pain in the UK.⁴⁴ The core theme running through the framework is effective communication and collaboration between multidisciplinary teams. The framework recommends the establishment of highly specialised services, dedicated to cancer pain, that integrate with primary and secondary services to advance cancer pain care. Whilst these specialist services do currently exist, they are only within select centres meaning access can be challenging and ad hoc. The framework creates a referral route for clinically challenging patients to gain access to highly specialised cancer pain services and therefore advanced therapy such as intrathecal drug delivery (ITDD) and cordotomy.

One consequence of implementation of the framework is the requirement to train more clinicians in the management of cancer associated pain, which may prove challenging in a healthcare environment operating with limited resource.

Low-middle-income countries

Globally there is an emerging middle class in low-middle-income countries (LMICs) (also less economically developed countries [LEDCs]), which is leading to better healthcare. This has led to a decrease in childhood mortality, increasing life expectancy and therefore increasing cancer incidence and survival rates. Pain in cancer survivors is therefore a growing issue for less advanced health systems. Technological solutions with digital therapeutics as mechanisms for consultation, monitoring, support and advice may help bridge the gap in LMICs whilst services are evolving to meet the needs of the population.

Conclusions

Pain in cancer survivors is an unpleasant consequence of improved therapeutics and is in itself a complex area of clinical practice. The pain experienced is multifactorial and highly individual, which mandates a therapeutic response that is equally personalised. The key to successful cancer survivor pain management is multidisciplinary working, effective communication and personalised care. Clinicians should consider that each patient has their own individual biological, psychological and social needs, and unless all of these are fully addressed, the patient's pain will probably continue to cause emotional and physical distress. Pain in cancer survivors represents a growing challenge to healthcare systems and providers; it is a challenge that pain medicine as a specialty should strive to meet.

Financial support and sponsorship

NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Biomedical Research Centre.

Declaration of interests

MB has conducted paid consulting work for Medtronic, Phytome life sciences, Canopy, Esteve and is deputy medical director of Medefer. TC and AN declare no conflicts of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Thomas Craig AFHEA MRCP FRCA FFPMRCA is a clinical research fellow in cancer-associated pain at the Royal Marsden Hospital.

Andrea Napolitano MD PhD is a consultant medical oncologist specialising in sarcoma at the Royal Marsden Hospital.

Matthew Brown MD (Res) BSc (Hons) MRCS FRCA FFPMRCA FFCI is a consultant in pain medicine at the Royal Marsden Hospital and associate honorary faculty at the Institute of Cancer Research.

Matrix codes: 1D02, 2E03, 3E00