Chronic pain in cancer survivors – a growing issue

With Dr Marieke van den Beuken-van Everdingen   |  11 Feb 2015  |  Print

Chronic pain in cancer survivors – a growing issue

Dr Marieke van den Beuken-van Everdingen is an internist and consultant in palliative care and oncologic pain at the University Pain Centre Maastricht (UPCM), University Hospital Maastricht, The Netherlands.

Advances in early detection and treatment of cancer have resulted in a growing group of cancer survivors. With a decrease in cancer mortality, a rise in cancer incidence and an ageing population, the number of people living with and beyond cancer will continue to grow by more than 3% a year.[1]

There has been little research regarding the problems faced by cancer survivors. We have some knowledge of the prevalence and nature of depression, pain and fatigue. However, the evidence is mostly of moderate quality and most often only for breast cancer and it focuses almost exclusively on the early phase of survivorship.[2]

Epidemiology

A review of pain in patients with cancer revealed that 33% of cancer survivors have pain (the review included seven studies and a total of 726 patients).[3] In other studies of short-term cancer survivors (six months to five years) pain was present in breast cancer survivors in 19-41%[4] and moderate to severe pain was present in 20% of a mixed group of cancer survivors.[5]

In long-term survivors (more than five years) studies show different results: pain was found in 27% of colorectal cancer survivors,[4] up to 35% in a mixed group of former cancer patients[6] and ‘quite a bit’ or ‘very much’ pain was found in 6% of another mixed group of cancer survivors. No differences in the rate of pain between different cancer types was found.[7]

Impact of pain

The literature is ambivalent when it comes to interpreting the impact of pain in long-term survivors. In long-term survivors, persistent pain may be particularly difficult to deal with. Often these patients have not anticipated having to deal with chronic pain after they no longer were actively involved with cancer care. Some cancer survivors may never fully appreciate being cancer free because of issues associated with chronic pain.

Furthermore, there can be serious economic stressors associated with constant cancer pain. One study, designed to evaluate the socioeconomic impact of head and neck cancer, showed that more than 40% of patients experienced a significant drop in income, with 30% being unable to work.[8

In contrast there is a growing body of research that has found that by five years post-diagnosis, global QoL generally appears to return to levels similar to those experienced by the general population or even better.[7] This increase in global QoL of long-term survivors could suggest that a response shift occurred. That is, as a result of cancer the survivors may have a different concept of the meaning of QoL compared with the general population. However, Zucca et al[7] conclude that self-reported QoL may just reflect high levels of well-being in long-term survivors, as there are consistently high levels of QoL and there are numerous comments from patients that they had ‘no issues’ and were ‘doing well’.

Causes and treatment of chronic pain in cancer survivors

As with all patients, cancer survivors may experience pain from common conditions unrelated to cancer, such as low back pain. In addition, survivors may experience comorbid chronic pain acquired or exacerbated during cancer treatment, including postherpetic neuralgia and painful diabetic neuropathy.[9] However, most chronic pain in cancer survivors is treatment-related. Surgery, radiotherapy, chemotherapy, hormonal therapy and other treatments, in combination or alone, have the potential to lead to severe persistent pain states.[10]

Persistent pain as a consequence of surgical treatment has been established for several common surgical procedures and represents a medical entity with potentially detrimental effects on quality of life. Incidences for common surgical procedures have been estimated as: 25-50% for thoracotomy and approximately 25-60% after breast cancer treatment (as a comparison, rates are approximately 10% for inguinal herniotomy).[11]

Chemotherapy-induced peripheral neuropathies (CIPN) are becoming increasingly more common as more neurotoxic agents are introduced to treat cancer. The incidence and time course depends on the agent and dose (Table). Patients typically under-report symptoms as they fear they may be removed from what they imagine to be a potentially curative agent. To date, no drug has been proven to prevent CIPN in human trials. Despite the lack of support for the efficacy of these drugs in treating CIPN, clinicians facing patients with severe, painful CIPN often rely on agents commonly used for other neuropathic conditions, including anticonvulsants, antidepressants, opioids, local anesthetics and other pharmacologic therapies.[10]

Radiation-induced pain syndromes include plexopathies, osteoradionecrosis and fractures, and pelvic pain. Delayed painful brachial and lumbosacral plexopathies have been described after radiotherapy, with the overall prevalence ranging from 2-5%. The onset is typically delayed from six months to as long as 30 years after radiotherapy, with peak onset from two to four years. Again, treatment options have not been systematically evaluated. Pharmacologic therapies, including opioids and adjuvant analgesics, are often recommended, but have not been studied.[10]

Table. Chemotherapeutic agents known to induce peripheral neuropathy[10]

 DRUG INCIDENCEA SYMPTOMSB
 Platinum-based drugs
 Carboplatin 5-20% Usually only with higher doses.
 Cisplatin 30-100% Dose dependent, may progress for months after treatment discontinued; sensory ataxia with gait dysfunction, impaired proprioception; may have motor changes with weakness and cramps; may experience autonomic changesc; can produce ototoxicity; less likely to resolve.
 Oxaliplatin 85-95% acute (during infusion) Cold-induced acute parasthesias and dysthesias of hands and feet; can cause pharyngolaryngeal dysesthesias; resolves within days to one week.
15-20% long term Similar to cisplatin; reversible in 66%; usually within 3 months.
Proteasome inhibitors
Bortezomib 31-55% CIPN is leading cause of discontinuing therapy; dose dependent, may progress for months after treatment discontinued; sensory ataxia with gait dysfunction, impaired proprioception; may have motor changes with weakness and cramps; may experience autonomic changes;c resolves in 3-6 months, may persist for some individuals.
Taxanes
Docetaxel 11-64% All three agents produce symmetrical painful paresthesia of feet and hands, may progress to legs, decreased proprioception, weakness, ataxia, gait dysfunction; usually resolved in 1-3 months although may persist; docetaxel and albumin-bound paclitaxel more likely to resolve and to reverse sooner than paclitaxel.
Paclitaxel 57-83%
Albumin-bound paclitaxel 73%
Vinca alkaloids
Vinblastine 30-47% overall for these agents; 60-71% for vincristine All agents produce symmetrical painful paresthesia of feet and hands, tingling, weakness, gait dysfunction; can produce cranial neuropathies; weakness with foot drop; may have autonomic changes (20-30%); resolution within 3 months, more likely to persist with vincristine.
Vincristine
Vindesine
Vinorelbine
Other agents
Ixabepilone 20-63% Painful paresthesia and burning; resolves within 4-6 weeks.
Lenalidomide 10-23% Similar to thalidomide; resolution unknown.
Thalidomide 25-83% Symmetrical tingling or numbness, pain, weakness, sensory ataxia and gait dysfunction; persists for one year or longer.

a Incidence lists grade 3 or 4 neuropathy in most cases; may be higher incidence if given in combination with other neurotoxic agents.
b Symptoms are dose dependent in almost all cases.
c Autonomic changes include orthostatic hypotension, constipation, urinary bladder dysfunction and erectile dysfunction.

The third generation aromatase inhibitors (AIs) have become an established component of treatment for early and advanced postmenopausal hormone-sensitive breast cancer. Unfortunately, the AI-induced musculoskeletal syndrome (AIMSS) represents a substantial problem in the clinical setting. Up to 50% of AI users complain of AIMSS, leading to treatment discontinuation in one out of four patients.[12]

Conclusion

Chronic pain in cancer survivors is still a black box: prevalence figures differ greatly, and current research would suggest that the influence on quality of life seems negligible; however, a firm socioeconomic burden has been demonstrated.

For those cancer survivors suffering with chronic pain, treatment strategies are lacking. Clinicians faced with patients who have treatment-induced pain rely on existing agents with little evidence for efficacy in this particular patient group. However, the successes of cancer treatment will mean a growing number of cancer survivors, and research should focus on managing survivorship.

References:

1. Maddams J, Brewster D, et al. Cancer prevalence in the United Kingdom: estimates for 2008. Br J Cancer 2009;101:541-547.
2. Richardson A, Addington-Hall J, et al. Knowledge, ignorance and priorities for research in key areas of cancer survivorship: findings from a scoping review. Br J Cancer  2011;105(Suppl 1):S82-S94.
3. Beuken-van Everdingen van den M, Rijke de J, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007;18:1437-1449.
4. Harrington CB, Hansen JA, et al. It’s not over when it’s over: long-term symptoms in cancer survivors–a systematic review. Int J Psychiatry Med 2010;40:163-181.
5. Beuken-van Everdingen van den MHJ, de Rijke JM, et al. High prevalence of pain in patients with cancer in a large population-based study in The Netherlands. Pain2007;132:312-320.
6. Mao JJ, Armstrong K, et al. Symptom burden among cancer survivors: impact of age and comorbidity. J Am Board Fam Med 2007;20:434-443.
7. Zucca AC, Boyes AW, et al. All’s well that ends well? Quality of life and physical symptom clusters in long-term cancer survivors across cancer types. J Pain Symptom Manag 2012;43:720-731
8. Vartanian JG, Carvalho AL, et al. Socioeconomic effects of and risk factors for disability in long-term survivors of head and neck cancer. Arch Otolaryngol Head Neck Surg 2006;132:32-35.
9. Levy MH, Chwistek M, et al. Management of chronic pain in cancer survivors. Cancer J 2008;14:401-409.
10. Paice JA. Chronic treatment-related pain in cancer survivors. Pain 2011;152(3 Suppl):S84-S89.
11. Andersen KG, Kehlet H. Persistent pain after breast cancer treatment: a critical review of risk factors and strategies for prevention. J Pain 2011;12:725-746.
12. Lintermans A, Neven P. Pharmacology of arthralgia with estrogen deprivation. Steroids 2011;76:781-785.

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