Chronic pain following cancer treatment is common. In survivors with an excellent prognosis, a biopsychosocial approach to pain management is recommended. |
The use of long-term opioid therapy in this population raises the same concerns as it does in chronic non-malignant pain. |
Adjuvant analgesics have an important role, as neuropathic pain is common in cancer survivors. |
1 Introduction
2 Definition of Pain in Cancer Survivors
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Adults who have had cancer or pre-malignant tumour diagnosed and treated after the age of 18 years.
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They have completed primary/first-line treatment (typically for early-stage disease and given with curative intent).
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They do not currently have evidence of active disease.
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Their pain is attributed to the administration of anti-cancer treatment.
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The pain has persisted beyond the usual time expected for the tissue damaged by the treatment to recover.
3 Common Cancer Treatment-Related Pain Syndromes
Pain syndrome | Treatment modality | Incidence/prevalence | Risk factors |
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Neuropathic pain | |||
Persistent pain post-cancer surgery | 20–68% 15–20% moderate-severe at 1 year | Young age High BMI ALND Acute post-operative pain Psychological characteristics | |
Thoracotomy | 25–57% Severe: < 10% | Adjuvant chemotherapy/RT Acute post-operative pain Psychological characteristics | |
Neck dissection [24] | 0–100% | Not yet identified | |
Colorectal surgery [25] | 22% at 6 months | Young age Peoperative abdominal pain Preoperative anxiety Longer duration of surgery High pain intensity on movement within 24 h after surgery | |
Nephrectomy [26] | 4% at 6 months | Not yet identified | |
60% at completion 30% at 6 months | Older age Type of chemotherapy (platinum > taxane) Number of cycles PN, diabetes, statins Smoking, alcohol | ||
Chronic pain post-RT [18] | Gynecologic Head and neck Lung apex Breast | 39% 15% 12% 2% | Type of cancer Total dose Large dose per fraction Surgery, chemotherapy |
Nociceptive pain | |||
Musculoskeletal pain post-surgery or RT | Variable | Not identified | |
Aromatase inhibitor-associated musculoskeletal syndrome [17] | Up to 50% 28% discontinue treatment | Younger age BMI > 30 Prior taxane chemotherapy | |
Rheumatic and musculoskeletal pain associated with checkpoint inhibitors [43] | Up to 22% | Not yet identified | |
Joint and fascia manifestations of chronic graft vs host disease [45] | 29% | Not yet identified |
3.1 Neuropathic Pain After Cancer Treatment
3.1.1 Persistent Pain Post-cancer Surgery
3.1.2 Chemotherapy-Induced Peripheral Neuropathy (CIPN)
3.1.3 Chronic Pain Post-radiation Therapy
3.2 Nociceptive Pain
4 Pathophysiology of Cancer Treatment-Related Pain Syndromes
Cancer surgery | Glutamate release, NMDA receptor changes, and calcium ion influx in dorsal horn of spinal cord |
mRNA-mediated protein synthesis in spinal cord | |
Chemotherapy | Axonal degeneration |
Mitochondrial damage | |
Increased reactive oxygen species | |
Altered calcium homeostasis | |
Altered ion channel expression | |
Increased inflammatory cytokines | |
Increased TLR4 receptor expression on glial cells |
4.1 Post-surgical Pain Mechanisms
4.2 Post-chemotherapy Pain Mechanisms
5 Current Approaches to the Pharmacotherapy of Chronic Pain in Cancer Survivors
5.1 Opioids
The role of LTOT is unclear |
The main indication is moderate-severe treatment-related pain not responding to maximally tolerated therapy with non-opioid approaches |
Opioids that were initiated during cancer treatment should be tapered off in survivors. This should be done gradually to avoid pain exacerbation and other adverse events (depression, suicide, illicit drug use, accidental overdose) |
LTOT is not normally recommended for comorbid chronic non-malignant pain, which is common in cancer survivors |
If LTOT is indicated in cancer survivors, it needs the same close monitoring as for patients with chronic non-malignant pain |
Although opioid misuse by people with chronic pain may be distinguished from opioid use disorder seen with recreational drug use, the pathophysiologic mechanisms are similar and the treatment the same, with opioid replacement therapy |
Risk factors for misuse are young age (under 35 years) and personal history of substance abuse |
Risk factors for opioid overdose include prolonged use and concomitant alcohol and benzodiazepine use |
5.1.1 Reducing or Discontinuing Opioids
5.1.2 Monitoring of Long-Term Opioid Therapy
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Establish and document desirable functional outcomes.
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Re-evaluate the effectiveness and necessity of opioids on a regular basis.
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If the expected outcome is not achieved, other treatment alternatives should be considered. If opioids are no longer appropriate, recommend gradual tapering of opioids to help avoid symptoms of withdrawal.
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Consider establishing pain treatment agreements.
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Adjuvant medications and non-pharmacological interventions should be considered.
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Use a multimodality approach to pain management if warranted, and if those resources are available. Consider referral to a specialist in interventional pain, physical medicine and rehabilitation, or other appropriate consultants.
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It is important to be aware that pain experience in a cancer survivor can be influenced by both medical and psychosocial events during and after cancer treatment. Psychological support of the survivor with chronic pain is necessary, and referral to psychosocial services should be considered.
5.1.3 Overcoming Barriers to Long-Term Opioid Therapy When It is Clinically Appropriate
5.1.4 Opioids and Pregnancy
5.2 Adjuvant Analgesics
Drug class [references] | Drugs, daily dose (mg/day), duration | Pain syndrome | Number in study | Mean pre-post reduction in pain score/10 | Percentage with reduced pain score | NNT |
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Non-steroidal anti-inflammatory drugs [104] | Celecoxib 400 mg vs diclofenac 100 mg, 6 weeks | Breast cancer survivors, post-chemotherapy or radiation therapy | 53 | 1.4 vs 1.5 | ||
Amitriptyline 10–50 mg vs placebo, 7 weeks | CIPN | 44 | 3.4 vs 1.9 | |||
Nortriptyline 100 mg vs placebo, 4 weeks | CIPN | 51 | 0.7 vs 0.3 | 69 vs 27% | 2.4 | |
Duloxetine 60 mg vs placebo, 5 weeks | CIPN | 231 | 0.7 vs 0.3 | 59 vs 38% | 4.8 | |
Duloxetine 60 mg vs placebo, 12 weeks | AIMSS | 255 | 2.8 vs 2.0 | 68 vs 59% | 11 | |
Venlafaxine 75 mg vs placebo, 10 weeks | Post-mastectomy pain | 13 | 4.9 vs 4.8 | |||
Gabapentinoids [117] | Gabapentin up to 2700 mg vs placebo, 6 weeks | CIPN | 115 | 1.0 vs 0.6 | ||
Medicinal cannabis products [139] | Nabiximols, up to 32.4 mg THC vs placebo, 4 weeks | CIPN | 16 | 0.75 vs 0.37 | 31 vs 0% |