|
 
 |
| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 6
| Issue : 3 | Page : 59-65 |
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Persistent chronic pain in cancer survivors: An update and future directions
Suman Choudhary, Ashok Kumar Saxena, Megha Bajaj, Ashima Thakur, Mayank Sonkar
Department of Anaesthesiology and Pain Medicine, University College of Medical Sciences, University of Delhi and GTB Hospital, New Delhi, India
| Date of Submission | 14-Oct-2021 |
| Date of Decision | 01-Dec-2022 |
| Date of Acceptance | 09-Dec-2022 |
| Date of Web Publication | 21-Dec-2022 |
Correspondence Address:
Suman Choudhary
No. 377 Kamla Nehru Nagar Chopasani Road, Jodhpur - 342 001, Rajasthan
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/oji.oji_41_21
Persistent chronic pain is the most common residual complaint in cancer survivors; its etiology being neoplastic process, postcancer treatment, or any other concurrent disorders. Growing concern about pain management in cancer survivors throws a mammoth challenge because more than 40% of cancer survivors now live longer than 10 years. Due to limited studies on persistent chronic pain in cancer survivors other than breast cancer, this enormous challenge remains in pain management in these cancer survivors. There are innumerable predictive factors for the development of persistent pain after cancer surgeries. It would be more prudent to concentrate on chronic pain mechanisms despite holding on to categorial risk factors and implanting them into patient outcomes. An effort should be made to a more holistic management of nociceptive and neuropathic pain in cancer survivor patients of Head and Neck, Prostate, and Lung carcinoma patients. In this article, we have tried to review the literature on managing chronic persistent pain in all cancer survivors, excluding carcinoma of the breast. In conclusion, we would like to emphasize that for an improved or excellent outcome of chronic persistent pain in cancer survivors, a holistic, multimodal approach encompassing pain relief techniques and pain relief strategies, relaxation exercises, cognitive behavioral therapy, and neuro-rehabilitative strategies would prove to be of immense help. A joint understanding between the pain management expert and the cancer survivors can result in beneficial outcomes.
Keywords: Cancer survivors, oncological modalities, persistent chronic pain
How to cite this article:
Choudhary S, Saxena AK, Bajaj M, Thakur A, Sonkar M. Persistent chronic pain in cancer survivors: An update and future directions. Oncol J India 2022;6:59-65 |
How to cite this URL:
Choudhary S, Saxena AK, Bajaj M, Thakur A, Sonkar M. Persistent chronic pain in cancer survivors: An update and future directions. Oncol J India [serial online] 2022 [cited 2023 Jun 4];6:59-65. Available from: https://www.ojionline.org/text.asp?2022/6/3/59/364564 |
| Introduction | |  |
Cancer remains the second-most mortality-causing disease in India, with about 0.3 million deaths per year.[1] All types of cancers have been reported in the Indian population, including the cancer of lung, skin, breast, rectum, stomach, prostate, bladder, blood, etc., out of which more than 40% of the total cancer burden was contributed by the seven leading cancer sites such as lung (10.6%), breast (10.5%), esophagus (5.8%), mouth (5.7%), stomach (5.2%), liver (4.6%), and cervix uteri (4.3%).[2]
Various treatment modalities for cancer patients starting from early screening, detection, and treatment, including surgery or chemo-radiotherapy, are readily available. Despite the latest up-gradation and improvement in the strategies for pain relief, chronic pain in cancer survivors remains a considerable challenge.
The prevalence of pain in cancer survivors has been as high as 40%.[3] Among all these cancer survivors, the greater prevalence of chronic pain is confined to cancer patients with metastasis. Studies suggest that up to 40% of those living beyond cancer are in pain and 5-10% have chronic severe pain that interferes with functioning, while one-third of 50% of cancer patients suffer from moderate-to-severe grading pain.[4],[5] Pain in cancer patients remains a burdensome problem in the current era of therapeutic advances in analgesia. Chronic pain in cancer of various types, such as breast, colon, lung, and liver, has been reported. In this review article, we have tried to provide insight into treatment and management in various cancer survivors, excluding breast cancer.
The etiology of cancer pain can be pain from an underlying malignant condition or its treatment. Common forms of pain are persistent postsurgical pain, chemotherapy-induced peripheral neuropathy (CIPN), radiation toxicity-associated pain, graft versus host disease-induced neuropathy, and aromatize inhibitor-induced arthralgia.[6]
| Chronic Persistent Pain in the Head and Neck Cancer Survivors | | |
In patients with head-and-neck cancer, orofacial pain can appear as a symptom of regional or distant cancers by nociceptive/somatic, neuropathic, inflammatory, and visceral mechanisms.
Cancer in the orofacial region presents with spontaneous pain, which affects the daily routine function of eating, drinking, swallowing, and talking and is very painful. Regional orofacial pain and other sensory disturbances like trigeminal neuropathic pain, neuralgic symptoms such as sharp shooting pain, and neurovascular disorders such as headache occur in 80% of patients with head-and-neck cancers.
Orofacial pain of neuropathic origin can be a result of tumor resection, chemotherapy, radiotherapy, or combination therapy. Oral mucositis as a result of chemoradiotherapy is extremely painful even while eating, which leads to long-term nutritional deficiency. Postradiation musculoskeletal complaints such as trismus, contracture, fibrosis, and scarring of muscles of mastication and temporomandibular joints ligaments affect the mouth opening and eating process.[7],[8]
| Chronic Persistent Pain in Lung Cancer Survivors | | |
Patients with lung cancer experience more symptoms of distress than patients with other types of cancers. The three main causes of pain in patients with advanced lung cancer are skeletal metastatic disease (34%), pancoast tumor (31%), and chest wall disease (21%). It is estimated that approximately 75% of cancer patients live with chronic pain; this pain is secondary to nociceptive or neuropathic syndromes, which represent the direct effects of cancer. Chest pain is a frequent and disabling symptom, worsening with disease progression, and is present in approximately 20% of patients presenting with lung cancer. Pain is frequently on the ipsilateral chest at the tumor site. Periosteal inflammation and elevation are the most common mechanism of pain from bone metastases. Lung cancer metastases to bone are predominately lytic. Cancer-induced bone pain has been shown to have unique characteristics and is a complex pain state. Sensory and sympathetic neurons are present within the bone marrow, mineralized bone, and periosteum, and all these compartments are affected by tumor cells. Metastatic bone pain is, therefore, complex to manage due to nociceptive, neuropathic, and visceral stimulation overlapping.[9]
Types of causes of pain in lung cancer survivors are depicted in [Table 1].
| Chronic Persistent Pain in Colorectal Cancer Survivors | | |
With advanced treatment, colorectal cancer (CRC) is transformed from a deadly disease to a curable illness. Over 90% of invasive CRCs are diagnosed in patients over the age of 50, with 67% being diagnosed in patients over the age of 65. CRC is the most common cancer diagnosed in patients over age 75.[10] Long-term CRC survivors have begun to address the late- and long-term effects of newer treatment regimens. Oxaliplatin-induced peripheral neuropathy has become common and occasionally dose-limiting toxicity in the CRC survivor population, usually manifesting as sensory impairment of the peripheral nerves in a stocking-glove distribution. Symptoms of numbness, pain, paraesthesia, dysesthesias, and changes in proprioception may affect fine motor skills such as writing, holding objects, buttoning shirts, picking up coins, and walking. Rarely, urinary retention and Lhermitte's sign (electric-shock sensation shooting down the spine with neck flexion) can occur. Both preoperative and postoperative radiation for rectal cancer increases the risk of long-term bowel dysfunction. Survivors who underwent an anterior resection surgery reported a median of three bowel movements per day, frequency, urgency, evacuation difficulties, and inability to differentiate stool and gas. These symptoms were most problematic during the 1st year after resection and were associated with fear, poor body image, and low self-confidence. Postradiotherapy for rectal cancer patient risk for pelvic insufficiency and fracture due to radiation bone damage may be increased.[11]
| Chronic Persistent Pain in Prostate Cancer Survivors | | |
Prostate cancer is one of the most common causes of cancer in men and is the second most common cause of cancer death after lung cancer. Advanced prostate cancer can be debilitating. Bone pain, fatigue, and weight loss are common, and increasing dependence and a feeling of losing control can contribute to anxiety and depression. Other symptoms include urinary outflow obstruction, weakness secondary to spinal cord compression, lymphedema, and anemia. Bone disease with pain is present in 90% of patients with metastatic prostate cancer. Bone lesions in the spine can lead to nerve root compression and neuropathic pain. This pain typically radiates along a nerve root and is sharp, burning, or tingling in nature. Bone pain in prostate cancer is usually dull, constant and gradually intensifying in nature. With the increasing size of the prostate tumor, the second type of breakthrough pain begins to occur as it “breaks through” the analgesic regimen the patient is receiving to control the ongoing pain. It is frequently divided into two types: A “pontaneous pain” that occurs without any obvious precipitating event and a “movement-evoked pain” precipitated by the movement of the tumor-bearing bone. Breakthrough pains are very severe and unpredictable, disabling the patient's functional status and quality of life, resulting in a significant increase in health-care utilization.[12],[13]
| Chronic Persistent Pain in Carcinoma Ovary Survivors | | |
As the population ages, there is an increase in the number of older women with ovarian cancer. Nearly 50% of the patients with ovarian cancer are diagnosed above the age of 65 years, and over 70% of them die from the same. Compared to younger females, the older population with ovarian cancer receives less surgery and chemotherapy, develops worse toxicity, and has poorer outcomes. Surgery is paramount because the amount of residual tumor is a major prognostic factor for survival. Older patients are at risk of increased surgical morbidity and mortality. For confirmed ovarian cancer patients, definite surgery includes total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, retroperitoneal lymph node sampling, diaphragm inspection, peritoneal biopsies, and washings.[14] Hysterectomy is a common gynecological surgery, and chronic pain reported following hysterectomy is seen in 5%–32%. Nerve injury-induced neuropathic pain has been considered to be the main pathogenic mechanism for the development of chronic persistent postsurgical pain.[15]
Pain syndromes associated with cancer treatment are listed in [Table 2].[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29] | Table 2: Chronic pain syndromes related to cancer treatment[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29]
Click here to view |
| Chemotherapy-Induced Peripheral Neuropathy | | |
CIPN represents a major cause of pain affecting peripheral sensory neuropathy in 68% of cancer during 1st month and in 60%, of 3 months after chemotherapy. Pain is bilateral, presenting as tingling, burning, or numbness in character, which is generally dose dependent and not completely reversible. Risk factors for CIPN include preexisting neuropathies, old age, being treated with paclitaxel, etc., Mechanisms of CIPN are tested on animal models for treatment in advance prospects. For example, oxaliplatin, paclitaxel, and vincristine cause an increase in abnormally high spontaneous discharges in A-beta and C fiber nociceptors, causing peripheral neuropathies. Mitochondrial function disruption, sodium-potassium pump alterations, cytokine-mediated inflammation, and deficiency in nerve growth factors and brain-derived neurotrophic factor have also been implicated in the mechanism of CIPN.
Drugs commonly associated with CIPN are listed in [Table 3].[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53] | Table 3: Drugs responsible for chemotherapy-induced peripheral neuropathy[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53]
Click here to view |
| Approaches to Treatment | | |
All cancer treatment modalities have the potential to cause pain. A personalized, patient-based approach to pain management remains the keystone for cancer pain. The WHO first launched the analgesic step ladder approach for providing cancer pain relief worldwide, yet it has limitations in the context of longer survival and increasing incidence of disease. The current ladder method failed to provide satisfactory relief in 10%–20% of patients of advanced stage, especially neuropathic pain and pain associated with bone involvement. Suggestions of adding a fourth, “interventional,” step be added to the 3-step WHO analgesic ladder is incorporated. Chronic pain management guidelines by the National Comprehensive Cancer Network 2013 aim at a multidisciplinary approach to achieve comfort, improve functionality, limit adverse events, and ensure safety.[54],[55],[56]
| NonPharmacological Interventions for Chronic Pain | | |
Several non-pharmacological interventions have been used for chronic pain management such as[57],[58],[59],[60],[61],[62],[63],[64],[65]
- Physical medicine and rehabilitation, such as physical therapy, occupational therapy, and recreational therapy
- Integrative therapies such as massage, acupuncture, and music
- Interventional therapies such as nerve blocks, neuraxial infusion, and vertebroplasty
- Psychological approaches such as cognitive behavioral therapy (CBT), distraction, and relaxation
- Neurostimulation therapies include TENS, spinal cord stimulation, PNS, and transcranial stimulation.
| Pharmacological Interventions | | |
Many systemic nonopioids, antidepressants, anticonvulsants, and various nutraceuticals and botanicals are used for treatment in cancer patients. Opioid remains the mainstay of cancer treatment and are prescribed round the clock. Commonly used preparations include morphine, oxycodone, transdermal patches of fentanyl, and methadone. For breakthrough pain, immediate-release preparations should be considered. The risk-benefit ratio of long-term opioid treatment should be assessed, and its judicious use to optimize the approach to achieve analgesia or improve functional status with minimum side effects.[66],[67],[68],[69],[70],[71],[72],[73]
In a very recent study by Vitzthum et al.[74] involving a cohort of more than 100,000 military veterans of frequently encountered cancers, the authors concluded that in prostate and lung cancer patients who have already been treated with radiotherapy, there was an enhanced requirement of opioids in comparison to those patients who have surgical intervention. Strong opioid was required for head-and-neck cancer in comparison to gastrointestinal cancers; lung, head and neck, breast, and prostate cancers are associated with more somatic pain, whereas colorectal, gastric, liver, pancreatic, and uterine cancers were associated more with visceral pain. In patients with terminal-stage cancer, opioids may require dose reduction, switching, or opioid antagonist for respiratory depression risk.[75]
| Chronic Pain in Elderly Cancer Survivors | | |
In this modern era, “geriatric oncology” has almost been designated as an important onco specialty that looks after a special category of the geriatric population who already may be having cognitive impairment, dementia, Alzheimer's, behavioral changes, and barriers in communication. Paracetamol remains a good option as an adjuvant for pain control in old chronic cancer patients. Other medications used for treatment are listed in [Table 4]. Considering the systemic impairment, including renal and hepatic functions, treatment protocol should be followed accordingly and prescribed cautiously. Other analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, and anticonvulsants such as gabapentin and pregabalin for neuropathic pain conditions or for chronic widespread pain, in cancer survivors.[76],[77],[78],[79],[80],[81],[82],[83],[84],[85],[86],[87],[88]
In the opinion of Antman,[84] Patrono,[80] and Strawson,[85] NSAIDs at reduced doses; are supposed to be cardioprotective. On the other hand, with their continuous, long-term therapy, they do exaggerate the risk of cerebrovascular accidents (CVAs), and myocardial infarctions (MIs). However, there is hardly any literature regards exaggerated risk in cancer survivors, who have been using NSAIDS on a prolonged basis.
The list of drugs for cancer pain treatment in older patients, along with geriatric considerations and side effects, are depicted in [Table 4].[76],[77],[78],[79],[80],[81],[82],[83],[84],[85],[86]
| Conclusion | | |
We would like to emphasize that for an improved or excellent outcome of chronic persistent pain in cancer survivors, a holistic, multimodal approach encompassing pain relief techniques and pain relief strategies, relaxation exercises, CBT and neuro rehabilitative strategies would prove to be of immense help. At the same time, education is essentially required to minimize theft, channeling and diversion of opioids when used in the management of chronic persistent pain in cancer survivors and to encourage patients to have free justified and rational access to opioids, ensuring that these opioids are prevented from entering the community. It is high time that we bring an innovative educational program for chronic pain in cancer survivors. There can be a paradigm shift through the implementation and integration of pain neuroscience education into a multimodal, holistic approach for a bio-psycho-social approach in the management of chronic persistent pain.
It is possible that transferring that knowledge to cancer survivors, shall allow them to understand and effectively cope with their pain. This may require explaining to the patient that persistent chronic pain in cancer survivors is the submission of various processes within the nervous system, which may or may not include nocioception, or poorly explain current tissue damage or illness. We must eliminate the therapeutic barrier and optimize therapeutic compliance.
Acknowledgment
Our sincere thanks to cancer survivors.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]
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