Cancer pain is a significant concern for many individuals affected by the disease. This article offers A Comprehensive Guide To Cancer Pain Management Strategies, aiming to improve the quality of life for patients and survivors. Recent advancements in oncology have led to improved cancer control and increased survival rates, resulting in a growing population of cancer survivors. However, a substantial portion of these survivors experiences chronic pain related to previous treatments or other underlying conditions. Effective pain management is crucial for this population, requiring a different approach than that used for patients with a limited prognosis.
Understanding Cancer Pain
Pain is a prevalent symptom in cancer patients, with approximately 44% experiencing it. Moderate to severe pain affects around 31% of patients. While pain prevalence and intensity have shown a decline in recent years, poorly controlled pain remains a challenge for many. This can be attributed to inadequate analgesic treatment, comorbidities, limited access to medications, and the prioritization of other cancer treatments over pain management. Chronic pain can significantly diminish a patient’s quality of life, leading to psychological distress and reduced functionality. In some cases, poorly relieved pain may even impact survival rates.
With advancements in oncology, targeted treatments have emerged, improving tumor control and increasing survival. Consequently, the population of cancer survivors has grown. However, approximately 47% of cancer survivors report chronic pain, with 28% experiencing moderate to severe pain. This pain can be related to previous treatments like chemotherapy, radiotherapy, or surgery, or it may stem from unrelated chronic pain conditions. Common pain conditions among cancer survivors include chemotherapy-induced peripheral neuropathy, aromatase inhibitor-associated musculoskeletal syndrome, and rheumatic pain associated with checkpoint inhibitors.
Recent Advancements in Cancer Pain Management
Significant strides have been made in chronic cancer pain management in recent years. A notable development is the inclusion of a chronic cancer pain taxonomy in the International Classification of Diseases (ICD-11), a collaborative effort between the WHO and IASP. This standardized classification aims to enhance the visibility and recognition of cancer-related pain, particularly in low- and middle-income countries where pain management is often inadequate.
Another vital improvement is the adaptation of the WHO analgesic ladder, a valuable tool since 1986. Traditionally, cancer pain management has relied heavily on pharmacotherapy, with opioids as the primary treatment. However, the opioid crisis has prompted a reassessment of opioid use in cancer patients and survivors. There is now a growing interest in non-pharmacologic treatments for pain management.
Patient-reported outcomes (PROs) are increasingly recognized as essential in treatment decision-making. Unlike in the past, cancer patients are now more likely to report pain spontaneously. Health-related quality of life is gaining attention among patients, leading to treatment choices that consider patient preferences and symptoms alongside comorbidities and drug toxicity profiles.
Cancer pain management is evolving towards an integrative pain care approach, similar to that used for chronic non-cancer pain. Integrative care combines multiple healthcare strategies in a multidisciplinary context, incorporating treatments from alternative and traditional medicine, as well as supportive care. This comprehensive approach is better suited to the complexity of pain and promotes individual preference and engagement in developing a treatment plan.
Opioids in Cancer Pain Management: An Updated Approach
Opioids continue to be a cornerstone of moderate to severe cancer pain treatment. Effective use of opioid analgesics is critical for adequate pain relief, but it is essential to consider their potential risks. Guidelines from organizations like EAPC, ASCO, ESMO, and WHO are regularly updated to guide opioid prescribing based on the WHO three-step ladder, introduced in 1986.
Weak opioids (codeine, hydrocodone, tramadol) are typically recommended for opioid-naïve patients with mild to moderate pain. These are often combined with non-opioid analgesics like paracetamol/acetaminophen and/or non-steroidal anti-inflammatory drugs (NSAIDs). There is no evidence suggesting that initiating opioid therapy with a weak drug improves overall cancer pain management.
Strong opioids (morphine, oxycodone, hydromorphone) are recommended for moderate to severe pain. Treatment should start with a low dose, and gradually increase to achieve optimal pain relief while minimizing side effects. Studies have shown that oral morphine or fentanyl patches can provide meaningful pain relief within 10 to 14 days for many patients. However, side effects like constipation and nausea are common, and some patients may need to change treatments.
Opioid response varies among individuals, raising questions about the interchangeability of morphine-like opioids. A trial comparing oral morphine, oral oxycodone, transdermal fentanyl, and transdermal buprenorphine found that pain intensities decreased similarly across the treatment groups. However, a significant percentage of patients experienced poor or no response to treatment, highlighting the challenges of achieving stable pain management due to factors like opioid tolerance, side effects, disease progression, and pain components unresponsive to opioids.
The practice of reserving strong opioids for the WHO step III ladder has been debated, with suggestions to use low doses of strong opioids as an alternative to weak opioids. Studies have indicated that many patients need to switch from step II to step III within two weeks due to inadequate pain control. Weak opioids may also have unpredictable analgesic effects due to genetic polymorphisms and can be expensive in low- and middle-income countries. Recent research has suggested that a two-step approach may be a valuable alternative for cancer pain management.
Optimizing Opioid Utilization for Poorly Controlled Pain
Up to 26% of patients experience poor or no response to opioids due to factors like disease progression, psychological conditions, neuropathic components, and breakthrough pain (BTP). Opioid misuse and the development of tolerance or hyperalgesia may also contribute.
Opioid rotation, or switching, is a common strategy to optimize pain management. This involves changing the opioid drug or its route of administration. However, evidence suggests that while pain control may be achieved, side effects are rarely lessened, and no single opioid drug has been identified as superior. Equianalgesic tables, commonly used for dose conversions, are not based on strong scientific evidence, and dose adjustments may be necessary. Opioid combinations are generally not recommended due to limited evidence.
Methadone, a synthetic opioid analgesic with unique properties, is sometimes recommended as a second-line opioid or co-analgesic when high doses of first-line opioids are already prescribed. It binds to multiple receptors, possesses anti-NMDA properties, and may affect serotonin and noradrenaline reuptake. However, methadone prescription requires expertise due to its complex pharmacokinetic profile.
Buprenorphine, a strong opioid with mixed agonist and antagonist properties, is not typically used as a first-line analgesic in cancer pain. It is often prescribed as a transdermal formulation in cases of opioid switching, renal failure, or mixed pain including a neuropathic component. Buprenorphine is now recommended as a first-line treatment for chronic pain in cancer survivors.
Tapentadol, a novel analgesic with a dual mechanism of action, binds to the µ-opioid receptor and acts as a central norepinephrine reuptake inhibitor. It is effective in cancer pain management, particularly for mixed pain and neuropathic pain.
Ketamine, an anaesthetic and potent analgesic, interacts with several systems and has NMDA-receptor antagonism. Low doses of ketamine can provide significant analgesic effects with limited side effects. It may be a useful adjuvant in the treatment of refractory chronic pain.
Magnesium plays a role in pain management by regulating NMDA receptor channels. Hypomagnesemia, which can occur in advanced cancer, may be associated with refractory pain episodes.
Lidocaine infusion, a local anaesthetic and anti-arrhythmic agent, may be used to relieve refractory complex neuropathic or visceral pain in advanced cancer.
Cannabis-related medicines (CBM) have gained attention but provide limited effects on chronic pain, including cancer-related pain, and are associated with side effects.
Adverse Effects and Harms of Long-Term Opioid Use
Long-term opioid use can disrupt endogenous opioid functioning, leading to common side effects like nausea, constipation, sedation, and respiratory depression. Tolerance and hyperalgesia may also develop. Endocrine changes, such as androgen deficiency and bone demineralization, are often underestimated. There is also concern about the risk of depression associated with long-term opioid prescription.
Opioid use disorders (OUD) have gained attention in relation to the opioid crisis. While previously considered low in cancer-treated patients, recent studies show that OUD prevalence can reach 8% among patients with cancer-related pain.
Long-term opioid therapy may induce “hyperkatifeia,” a negative emotional state, potentially leading to increased opioid intake and overdose. Close follow-up of chronic opioid prescriptions is recommended in cancer survivors, emphasizing the use of the lowest possible doses, opioid tapering, and specific drugs like buprenorphine for maintenance.
Addressing Neuropathic Pain
Neuropathic pain affects between 20 and 40% of cancer patients. It is caused by a lesion or disease of the somatosensory nervous system, often related to the tumor itself or its treatment. Neuropathic mechanisms can significantly contribute to cancer-induced bone pain and may cause metastatic bone pain refractory to standard treatments.
A correct diagnosis of neuropathic cancer pain (NCP) is essential for appropriate treatment. Diagnosis involves a comprehensive evaluation, including medical history, physical examination, and diagnostic tests. The revised grading system for neuropathic pain is commonly used for assessment.
Guidelines recommend treating NCP with a combination of opioids and adjuvants when opioids alone are insufficient. First-line medications include tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and anticonvulsant drugs. Topical treatments, such as lidocaine patches and capsaicin, may also be used for localized neuropathic pain.
Opioids are commonly prescribed for patients with NCP due to the frequent presence of mixed pain. Tramadol and tapentadol, which have dual modes of action, may be particularly effective. Switching to methadone may also improve pain scores in patients with NCP.
Managing Breakthrough Pain
Breakthrough pain (BTP) is a transient exacerbation of pain that occurs despite controlled baseline pain. It is common in advanced disease and can be triggered by specific events or occur spontaneously. Treatment involves avoiding precipitating factors, preemptive administration of analgesics, and rapid-onset opioids administered transmucosally.
Efficient control of baseline pain is critical in managing BTP. Optimizing background analgesia may limit the number of BTP episodes. The dose of opioids used to relieve BTP remains a subject of debate, with options including a dose proportional to background analgesia or the minimum effective dose titrated as needed.
Personalized Treatment: Non-Invasive and Invasive Techniques
The WHO analgesic ladder may not provide adequate pain relief for all patients, prompting the development of updated versions that incorporate integrative medicine and interventional treatments. The “step up, step down” approach allows treatments to be tailored to the type of pain. Interventional treatments should be considered before refractory pain develops.
The European Society for Medical Oncology (ESMO) recommends an integrative approach that includes primary antitumour treatments, interventional analgesic therapy, and non-invasive techniques. Radiotherapy, hormonotherapy, chemotherapy, and surgery can effectively relieve pain in certain cancer patients. More specific strategies need to be considered on a case-by-case basis, with a multidisciplinary team essential for managing refractory pain.
Photobiomodulation (PBM), or low-level laser therapy (LLLT), reduces local inflammation and is useful for alleviating pain conditions secondary to cancer treatments like mucositis and radiodermatitis.
Neuromodulation involves altering nerve activity through targeted delivery of stimuli. Techniques include spinal cord stimulation, neuraxial drug delivery systems, peripheral nerve stimulation, and peripheral nerve field stimulation.
Neuraxial drug delivery, which involves infusing drugs directly near the spinal dorsal horn through an intrathecal catheter, can improve pain management and quality of life while reducing systemic opioid needs and side effects. However, it requires careful consideration of the patient’s diagnosis, survival expectations, and previous opioid use.
Percutaneous neurolysis techniques, such as cryoanalgesia, thermal neurotomy, and pulsed radiofrequency, can be used for neuropathic refractory pain in patients with short life expectancies.
Cordotomy, a surgical procedure that involves creating lesions to the spinothalamic tract, should be reserved for patients with short-term survival and severe pain.
Percutaneous ablation of metastasis can provide significant pain relief for metastatic bone lesions.
Vertebroplasty and kyphoplasty are minimally invasive techniques used to treat vertebral instability and spinal cord compression.
Botulinum toxin (BT) has analgesic effects and can reduce muscle spasms in the vicinity of radiotherapy or surgical areas.
Psychological Support and Non-Pharmacological Therapies
Integrative medicine includes non-pharmacological therapies that reinforce other strategies and improve patient comfort and quality of life. Mind-body practices, such as meditation, hypnosis, tai chi, and biofeedback, can help manage anxiety, depression, fatigue, and emotional wellness.
Hypnosis can induce a modified state of consciousness and is effective in managing pain and improving quality of life.
Yoga practice improves quality of life and has shown a beneficial effect on pain in patients with aromatase inhibitor-related joint pain.
Tai Chi and Qi Gong may improve emotional well-being and enhance quality of life.
Mindfulness and meditation are effective for cancer-related symptoms and can improve overall patient quality of life and reduce pain severity.
Cognitive behavioral strategies and pain coping are accessible techniques that can positively impact pain symptoms.
Music therapy can reduce pain, emotional distress, and analgesic drug consumption.
Acupuncture may be beneficial for cancer pain management, including in palliative care patients, and can reduce analgesic drug intake.
Massage therapy has shown a beneficial effect on cancer pain, fatigue, and anxiety.
Religious and spiritual interventions may have a small beneficial effect on pain, reduce physical symptoms, and increase quality of life.
Virtual reality is a future therapeutic approach that can improve overall well-being and reduce anxiety.
Conclusion
Cancer pain management is a complex and evolving field. With the increasing number of cancer survivors, effective pain management strategies are essential to improve quality of life. A dynamic, interdisciplinary approach that integrates pharmacological, physical, and psychotherapeutic treatments is crucial. Alternative interventional therapies should be available when primary approaches fail. By personalizing treatment and prioritizing patient quality of life, clinicians can provide comprehensive and compassionate care for individuals affected by cancer pain.
