Pain is one of the most common symptoms in cancer patients and often has a negative impact on patients’ functional status and quality of life. The goal of the following summary is to provide evidence-based, up-to-date, and practical information on the management of cancer pain.
Effective pain management can generally be accomplished by paying attention to the following steps:
- Regular screening to ensure that the patient’s pain is recognized early. (Refer to the Pain Assessment section of this summary for more information.)
- Proper characterization of the pain to identify underlying pathophysiology, which could significantly influence treatment options. (Refer to the Pain Classification section of this summary for more information). Is the pain acute or chronic? Is it secondary to cancer, cancer treatment, other causes, or a combination? Is it somatic, visceral, neuropathic, or mixed? Is there an incidental component?Is there breakthrough pain?
- Determining whether the pain requires pharmacologic and/or other modalities of treatment. Pain is often multifactorial in nature, so factors that may modulate pain expression, such as psychological distress and substance use, should be assessed. (Refer to the Background and Definitions section of this summary for more information.) What is the impact of pain on the patient? Is the benefit of treatment likely going to outweigh the risks?
- Identifying the optimal pharmacologic and nonpharmacologic treatment options (refer to the Pharmacologic Therapies for Pain Control section of this summary for more information), including referrals to specialists, if needed. (Refer to the Modalities for Pain Control: Other Approaches section of this summary for more information.) Complex pain often requires multidimensional interdisciplinary evaluation and intervention. There are many issues to consider when determining the most appropriate treatment, such as the following: Previous pain treatments. Patient prognosis. Predictive factors for pain control (e.g., psychological distress). Impact on function. Comorbidities (e.g., renal or hepatic failure). Risk of misuse of or addiction to pain medications. Patient preference.
- Providing proper education about treatment, including medication administration, expected side effects and associated treatments, and when patients can expect improvement. If opioids are considered, opioid phobia and the risks of opioid use and misuse should be addressed. Patients and family caregivers should be educated about the safe storage, use, and disposal of opioids. One study demonstrated that improper use, storage, and disposal are common among cancer outpatients.
- Monitoring the patient longitudinally with return visits to titrate/adjust treatments. Patients with cancer or noncancer pain requiring chronic therapy are monitored closely to optimize treatment and to minimize the likelihood of complications of opioid use, including misuse or abuse. The risks and benefits of opioid use are evaluated regularly, and physician impressions are discussed openly with the patient.
Background and Definitions
The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” Pain is commonly experienced by cancer patients. Its proper assessment requires measuring pain intensity; clarifying the impact of pain on patients’ psychological, social, spiritual, and existential domains; and establishing treatment adherence and responsiveness.
A commonly used approach to pain management employs the World Health Organization (WHO) pain relief ladderExit Disclaimer, which categorizes pain intensity according to severity and recommends analgesic agents based on their strength. Pain intensity is often assessed using a numeric rating scale (NRS) of 0 to 10.
On this scale, 0 indicates no pain, 1 to 3 indicates mild pain, 4 to 6 indicates moderate pain, and 7 to 10 indicates severe pain.
Step 1 on the WHO pain relief ladder treats mild pain. Patients in this category receive nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, or an adjuvant analgesic, if necessary. Step 2 treats patients experiencing mild to moderate pain who are already taking a nonopioid analgesic, with or without an adjuvant analgesic, but who are still experiencing poor analgesia. Step 2 agents include tramadol and acetaminophen products containing hydrocodone, oxycodone, and codeine. Step 3 treats moderate to severe pain with strong analgesics. Step 3 opioids include morphine, hydromorphone, fentanyl, levorphanol, methadone, oxymorphone, and oxycodone. An open-label randomized trial of low-dose morphine versus weak opioids to treat moderate cancer pain suggests that it is acceptable to bypass weak opioids and go directly to strong opioids (step 3 agents) for patients with moderate cancer pain, as patients randomly assigned to the low-dose morphine group had more frequent and greater reduction in pain intensity with similarly good tolerability and earlier effect.
Familiarity with opioid pharmacokinetics, equianalgesic dosing, and adverse effects is necessary for their safe and effective use. The appropriate use of adjuvant pharmacological and nonpharmacological interventions is needed to optimize pain management.
Pain occurs in 20% to 50% of patients with cancer. Roughly 80% of patients with advanced-stage cancer have moderate to severe pain. One meta-analysis looking at pooled data from 52 studies found that more than half of patients had pain. Younger patients are more likely to experience cancer pain and pain flares than are older patients.
Cancer patients often have multiple sites of pain. Patients rated pain from 4 to 6 (severe) on the NRS, with exacerbations rated as high as 7.
Causes of Cancer Pain: Cancer, Cancer Treatments, and Comorbidities
A study evaluating the characteristics of patients (N = 100) with advanced cancer presenting to a palliative care service found the primary tumor as the chief cause of pain in 68% of patients. Most pain was somatic, and pain was as likely to be continuous as intermittent.
Pain can be caused by cancer therapies, including surgery, radiation therapy, chemotherapy, targeted therapy, supportive care therapies, and/or diagnostic procedures. A systematic review of the literature identified reports of pain occurring in 59% of patients receiving anticancer treatment and in 33% of patients after curative treatments. The prevalence of chronic nonmalignant pain—such as chronic low back pain, osteoarthritis pain, fibromyalgia, and chronic daily headaches—has not been well characterized in cancer patients. It has been reported to be between 2% and 76%, depending on the patient population and how pain was assessed.[12-15]
Pain is an expected consequence of surgery. Concerns about the prevalence of opioid misuse have drawn increasing attention to how opioids are prescribed in common settings, including postoperatively. Studies suggest widespread variation in the prescribing patterns of opioids in the postoperative setting. One study of opioid use after orthopedic and general surgery procedures found that, on average, only between 19% and 34% of the opioids prescribed were used and that the quantity of opioids prescribed after a given procedure varied widely by provider. This finding led to the evaluation of utilization data and recommendations for standardizing the quantity of opioids prescribed for five common general surgery procedures. An educational intervention based on those recommendations was associated with a 53% decrease in prescribed opioids after those five general surgery procedures, with only 1 patient in a cohort of 246 patients requiring an opioid refill.
The opioid epidemic has also raised questions about whether postoperative use of opioids can lead to misuse. New persistent opioid use develops in 6% to 8% of opioid-naïve patients after noncancer surgery.[19-21] In a large retrospective analysis of patients undergoing curative-intent cancer surgery, 10.4% of opioid-naïve patients developed new persistent opioid use, defined as filling opioid prescriptions 90 to 180 days after surgery. At 1 year postsurgery, these patients were using an average of six 5-mg hydrocodone (or equivalent) tablets per day. Among the risk factors evaluated, only the use of adjuvant chemotherapy increased the risk of new persistent opioid use (15%–21% risk with adjuvant chemotherapy vs. 7%–11% risk with no chemotherapy). In summary, one in ten patients undergoing curative-intent cancer surgery may be at risk of postoperative persistent opioid use.
Infusion-related pain syndromes
The infusion of intravenous chemotherapy causes four pain syndromes: venous spasm, chemical phlebitis, vesicant extravasation, and anthracycline-associated flare.[23-25] Venous spasm is treated by application of a warm compress or decrease in the infusion rate. Chemical phlebitis may result from chemotherapy or nonchemotherapy infusions such as potassium chloride and hyperosmolar solutions. Vesicant extravasation may cause intense pain followed by desquamation and ulceration. Doxorubicin may result in the venous flare reaction, which includes local urticaria, pain, or stinging. Some chemotherapy agents such as vinorelbine may cause pain at the tumor site.
Severe mucositis often occurs as a consequence of myeloablative chemotherapy and standard-intensity therapy. Cytotoxic agents commonly associated with mucositis are cytarabine, doxorubicin, etoposide, 5-fluorouracil, and methotrexate. Epidermal growth factor receptor (EGFR) inhibitors, multitargeted tyrosine kinase inhibitors, and mammalian target of rapamycin inhibitors also cause mucositis.[28,29] Risk factors for mucositis include preexisting oral pathology, poor dental hygiene, and younger age.
Chemotherapy-related musculoskeletal pain
Paclitaxel generates a syndrome of diffuse arthralgias and myalgias in 10% to 20% of patients. Diffuse pain in joints and muscles appears 1 to 2 days after the infusion and lasts a median of 4 to 5 days. Pain originates in the back, hips, shoulders, thighs, legs, and feet. Weight bearing, walking, or tactile contact exacerbates the pain. Steroids may reduce the tendency to develop myalgia and arthralgias. Among hormonal therapies, aromatase inhibitors cause musculoskeletal symptoms, osteoporotic fractures, arthralgias, and myalgias.
Dermatologic complications and chemotherapy
EGFR inhibitors cause dermatitis with ensuing pain. Acute herpetic neuralgia occurs with a significantly increased incidence among cancer patients, especially those with hematologic malignancies and those receiving immunosuppressive therapies. The pain usually resolves within 2 months but can persist and become postherpetic neuralgia. The palmar-plantar erythrodysesthesia syndrome is observed in association with continuously infused 5-fluorouracil, capecitabine, liposomal doxorubicin, and paclitaxel. Targeted agents such as sorafenib and sunitinib are also associated with hand-foot–like syndrome. Patients develop tingling or burning in their palms and soles, followed by an erythematous rash. Management often requires discontinuing therapy or reducing the treatment dose.
Supportive care therapies and pain
Supportive care therapies can cause pain, as typified by bisphosphonate-associated osteonecrosis of the jaw. Corticosteroid use has also been associated with the development of avascular necrosis.
Radiation is associated with several distinct pain syndromes. First, patients may experience pain from brachytherapy and from positioning during treatment (i.e., placement on a radiation treatment table). Second, delayed tissue damage such as mucositis, mucosal inflammation in areas receiving radiation, and dermatitis may be painful. Third, a temporary worsening of pain in the treated area (a pain flare) is a potential side effect of radiation treatment for bone metastases. A randomized trial demonstrated that dexamethasone (8 mg on day of radiation therapy and daily for the following 4 days) reduces the incidence of pain flares, compared with placebo. (Refer to the External-Beam Radiation Therapy section of this summary for more information.)
Impact on Function and Quality of Life
Cancer pain is associated with increased emotional distress. Both pain duration and pain severity correlate with risk of developing depression. Cancer patients are disabled an average of 12 to 20 days per month, with 28% to 55% unable to work because of their cancer. Cancer survivors may experience distress when their pain unexpectedly persists after completion of cancer treatments. Survivors also experience loss of support from their previous health care team as oncologists transition their care back to primary care providers.
In one study, between 20% and 50% of cancer patients continued to experience pain and functional limitations years posttreatment. Untreated pain leads to requests for physician-assisted suicide. Untreated pain also leads to unnecessary hospital admissions and visits to emergency departments.
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