Cancer Pain (PDQ®)–Health Professional Version - National Cancer Institute

Cancer Pain (PDQ®)–Health Professional Version

Modalities for Pain Control: Other Approaches

Pain Procedures

While pharmacologic therapy using the World Health Organization (WHO) guidelines effectively manages most cancer pain, approximately 10% to 20% of patients will have refractory pain or excessive side effects.[1] For patients with refractory pain or specific regional pain syndromes, an interventional approach to treating pain has been proposed as the fourth step on the WHO pain relief ladder . Some common interventions and their evidence of benefit are discussed below.

Nerve blocks

The celiac plexus block, used primarily for patients with upper abdominal pain from pancreatic cancer, is the most commonly employed neurolytic blockade of the sympathetic axis, followed by the superior hypogastric plexus block and the ganglion of impar block for patients with lower abdominal or pelvic pain. Traditionally, the autonomic neural blockade was reserved for patients with inadequate response to oral opioids, but some researchers have suggested that the intervention—which is associated with decreased pain, reduced opioid consumption, improved performance status, and few complications—is considered a first-line approach.[2,3]

For patients with regional pain, a peripheral nerve block infusing a local anesthetic can achieve local pain control. This approach can be applied to any peripheral nerve, including the femoral, sciatic, paravertebral, brachial plexus, and interpleural nerves.[4]

Neuroaxial delivery of analgesia

When patients have pain that persists despite high doses of opioids and other analgesics or have intolerable side effects to oral opioids—such as delirium, sedation, or nausea—an alternative route of delivery may be considered. Compared with intravenous administration of opioids, epidural and intrathecal routes of delivery are 10 and 100 times more potent, respectively. Such routes of delivery allow high doses of analgesics to be administered with less systemic absorption and fewer side effects.[5]

One study that randomly assigned patients to receive either an implantable drug delivery system or comprehensive medical management found that patients receiving the analgesic through the implantable pump had less pain, less toxicity, and longer survival at 6 months.[6] While the survival benefit did not persist in other studies, the intrathecal pump may be an option for selected patients with refractory pain and a life expectancy longer than 3 months.[7] However, intrathecal pumps may make it difficult for patients to access hospice care because of care needs and cost issues, and they cannot effectively treat pain that is predominantly related to psychological distress.[8] For patients with shorter life expectancies, placement of an epidural catheter may be a safe and effective technique.[4]

Cordotomy

Cordotomy is reserved for pain refractory to other approaches and is done less commonly today. It is most effective in treating unilateral somatic pain from the torso to the lower extremities. The available literature suggests a high rate of efficacy, with 60% to 80% complete pain relief immediately after the procedure, falling to 50% at 12 months. Cordotomy is generally reserved for patients considered to be in the last 2 years of life, with pain refractory to other approaches, and may be done via the open route or the percutaneous route.[9-11]

For patients with either regional pain syndromes or pain refractory to escalating systemic medications, the cancer clinician may consult with a pain specialist or neurosurgeon to consider an interventional approach to pain control.

Palliative Care Referral

Palliative care , which is specialized medical care for people with serious illnesses with the goal to maximize quality of life for both patients and families, can provide expert assessment and management of pain and other nonpain symptoms. Palliative care providers work in interdisciplinary teams that include physicians, nurses, mental health specialists, social workers, chaplains, and sometimes pharmacists and dieticians. For patients with refractory pain, prominent nonpain symptoms, or intense psychosocial distress, a referral to palliative care may be appropriate, where available. Many palliative care teams now call themselves supportive care teams because this term is more acceptable to many referring providers and to some patients and families.[12,13]

Palliative care specialists may also help manage patients with multiple comorbidities, those requiring higher doses of opioids, and those with a history of substance use disorder or complex psychosocial dynamics that can complicate the management of pain and adherence to recommended medications. Most palliative care specialists have experience using methadone for pain.

The role of specialty palliative care integrated into cancer care has been well studied, with studies showing that early integration of specialty palliative care into cancer care reduces symptom burden and enhances quality of life for both patients and families [14-17] and may prolong life.[14] (Refer to the PDQ summary on Planning the Transition to End-of-Life Care in Advanced Cancer for more information.)

External-Beam Radiation Therapy

Palliative radiation therapy represents an effective modality for pain related to advanced cancer. Pain related to bone metastases, skin lesions, or isolated tumor lesions may be relieved by a short course of radiation therapy. Patient selection can be important regarding the likelihood of benefit from radiation therapy. In one study, patients with hematologic tumors, a neuropathic component of the index pain, and no previous treatment with opioid analgesics before radiation therapy were more likely to experience pain palliation after radiation therapy.[18]

For bone metastases, radiation is often delivered as 8 Gy in a single fraction, 20 Gy in five fractions, 24 Gy in six fractions, or 30 Gy in ten fractions. A Cochrane review that included 11 randomized trials consisting of 3,435 patients showed that single-fraction radiation therapy for bone pain provided a similar overall response rate (60% vs. 59%) and complete response rate (34% vs. 32%), compared with multifraction radiation therapy.[19] However, patients who received single-fraction radiation therapy had a higher rate of re-treatment (22% vs. 7%) and a higher rate of pathological fracture (3% vs. 1.6%).[19] This finding was consistent with other systematic reviews.[20] In the Dutch Bone Metastasis Study, the average time to first pain relief was 3 weeks; the peak effect was achieved in 4 to 6 weeks; and the mean duration of response was approximately 30 weeks.[21,22] Single-fraction radiation has several potential advantages: greater convenience, lower cost, and less breakthrough pain associated with transportation to the radiation facility and with getting on and off the radiation table.

Re-irradiation may be considered for selected patients who derive no or partial pain relief with first-time radiation therapy, or who develop worsening pain after an initial response. Re-irradiation typically occurs at least 4 weeks after the first radiation treatment. A systematic review that examined re-irradiation for bone metastases included 15 studies and reported a complete response rate of 20% and a partial response rate of 50%.[23] Re-irradiation was generally well tolerated.[23] In a secondary analysis of the National Cancer Institute of Canada Clinical Trials Group Symptom Control Trial SC.20, which examined outcomes of 847 patients who underwent palliative re-irradiation of painful bone metastases, the team found no differences in pain relief or side effects across age or gender demographics. Women and younger patients reported greater improvements in quality of life.[24] Serious adverse effects such as spinal cord compression and pathological fracture were infrequent (<3%). A randomized controlled trial compared a single fraction (8 Gy) with multiple fractions (20 Gy over 5 days) of re-irradiation and found similar response rates at 2 months in an intention-to-treat analysis (28% vs. 32%; P = .02).[25]

A potential side effect of palliative radiation for painful bone metastases is a temporary increase in pain level, i.e., a pain flare. Pain flares occur in about 40% of patients and may be quite distressing. One study [26] randomly assigned 298 patients, who were scheduled to receive a single 8-Gy dose of radiation, to receive either placebo or dexamethasone 8 mg on days 0 to 4. Fewer patients in the dexamethasone group experienced pain flares (26% vs. 35%; P = .05). Potentially serious hyperglycemia was seen in only two patients in the dexamethasone group. The study supports the use of prophylactic dexamethasone in this setting.

Radionuclides

Patients with multiple sites of symptomatic osteoblastic bone metastases may consider radionuclides such as strontium chloride Sr 89 or samarium Sm 153 (153Sm), which are beta-emitters. Two double-blind randomized trials support the superiority of 153Sm over placebo in providing pain control and reducing analgesic use.[27,28] The overall response varies between 30% and 80%, with onset of pain relief within the first week; some patients report a long-lasting benefit (up to 18 months). The most common toxicities are pain flare and cytopenias. Pain flare typically occurs in approximately 10% of patients within the first 24 to 48 hours of administration and may be treated with corticosteroids or opioids.[29] Leukopenia and thrombocytopenia are sometimes seen, with a nadir of 4 weeks posttreatment and recovery by 8 weeks. Contraindications to radionuclide therapy include a poor performance status (Karnofsky Performance Status score <50%) and a short life expectancy (<3 months).

Radium Ra 223-dichloride (223Ra-dichloride) (an alpha-emitter) is approved for use in patients with castration-resistant prostate cancer. A phase III randomized trial compared 223Ra-dichloride with placebo in a 2:1 ratio. Among the 921 symptomatic patients enrolled, those who received 223Ra-dichloride had a prolonged time to first symptomatic skeletal event (15.6 months vs. 9.8 months, P < .0001), in addition to prolonged overall survival (14.9 months vs. 11.3 months, P < .001).[30]

Physical Medicine and Rehabilitation

Patients with cancer and pain may experience loss of strength, mobility, and, ultimately, functional status secondary to the cause of pain, (e.g., vertebral metastases, incident pain, and chronic nonmalignant pain). Therefore, pain and functional status may improve with physical or occupational therapy, treatments for strengthening and stretching, and the use of assistive devices.[31] Referral to a physiatrist (a physician who specializes in rehabilitation medicine) who could create a comprehensive plan may benefit the patient. In addition, some physiatrists practice interventional pain medicine.

Integrative Therapy

Patients with cancer frequently use complementary or alternative medicines or interventions (CAM).[32] One of the stated benefits of CAM is pain relief. However, a meta-analysis of multi-institutional, randomized, controlled trials for cancer-related pain concluded that methodological flaws hampered interpretation of the few available studies. There were brief positive effects in favor of CAM for acupuncture, support groups, hypnosis, and herbal supplements.[33] (Refer to the PDQ summaries on Integrative, Alternative, and Complementary Therapies for more information.)

References

McHugh ME, Miller-Saultz D, Wuhrman E, et al.: Interventional pain management in the palliative care patient. Int J Palliat Nurs 18 (9): 426-8, 430-3, 2012. [PUBMED Abstract]
Tei Y, Morita T, Nakaho T, et al.: Treatment efficacy of neural blockade in specialized palliative care services in Japan: a multicenter audit survey. J Pain Symptom Manage 36 (5): 461-7, 2008. [PUBMED Abstract]
Bhatnagar S, Khanna S, Roshni S, et al.: Early ultrasound-guided neurolysis for pain management in gastrointestinal and pelvic malignancies: an observational study in a tertiary care center of urban India. Pain Pract 12 (1): 23-32, 2012. [PUBMED Abstract]
Chambers WA: Nerve blocks in palliative care. Br J Anaesth 101 (1): 95-100, 2008. [PUBMED Abstract]
Smyth CE, Jarvis V, Poulin P: Brief review: Neuraxial analgesia in refractory malignant pain. Can J Anaesth 61 (2): 141-53, 2014. [PUBMED Abstract]
Smith TJ, Staats PS, Deer T, et al.: Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 20 (19): 4040-9, 2002. [PUBMED Abstract]
Smith TJ, Coyne PJ: Implantable drug delivery systems (IDDS) after failure of comprehensive medical management (CMM) can palliate symptoms in the most refractory cancer pain patients. J Palliat Med 8 (4): 736-42, 2005. [PUBMED Abstract]
Reddy A, Yennurajalingam S, de la Cruz M, et al.: Factors associated with survival after opioid rotation in cancer patients presenting to an outpatient supportive care center. J Pain Symptom Manage 48 (1): 92-8, 2014. [PUBMED Abstract]
Siegfried J: Electrostimulation and neurosurgical measures in cancer pain. Recent Results Cancer Res 108: 28-32, 1988. [PUBMED Abstract]
Lahuerta J, Bowsher D, Lipton S, et al.: Percutaneous cervical cordotomy: a review of 181 operations on 146 patients with a study on the location of "pain fibers" in the C-2 spinal cord segment of 29 cases. J Neurosurg 80 (6): 975-85, 1994. [PUBMED Abstract]
Lahuerta J, Lipton S, Wells JC: Percutaneous cervical cordotomy: results and complications in a recent series of 100 patients. Ann R Coll Surg Engl 67 (1): 41-4, 1985. [PUBMED Abstract]
Fadul N, Elsayem A, Palmer JL, et al.: Supportive versus palliative care: what's in a name?: a survey of medical oncologists and midlevel providers at a comprehensive cancer center. Cancer 115 (9): 2013-21, 2009. [PUBMED Abstract]
Dalal S, Palla S, Hui D, et al.: Association between a name change from palliative to supportive care and the timing of patient referrals at a comprehensive cancer center. Oncologist 16 (1): 105-11, 2011. [PUBMED Abstract]
Temel JS, Greer JA, Muzikansky A, et al.: Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 363 (8): 733-42, 2010. [PUBMED Abstract]
Zimmermann C, Swami N, Krzyzanowska M, et al.: Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet 383 (9930): 1721-30, 2014. [PUBMED Abstract]
Bakitas M, Lyons KD, Hegel MT, et al.: The project ENABLE II randomized controlled trial to improve palliative care for rural patients with advanced cancer: baseline findings, methodological challenges, and solutions. Palliat Support Care 7 (1): 75-86, 2009. [PUBMED Abstract]
Bakitas MA, Tosteson TD, Li Z, et al.: Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial. J Clin Oncol 33 (13): 1438-45, 2015. [PUBMED Abstract]
Saito T, Toya R, Tomitaka E, et al.: Predictors of Pain Palliation After Radiation Therapy for Painful Tumors: A Prospective Observational Study. Int J Radiat Oncol Biol Phys 101 (5): 1061-1068, 2018. [PUBMED Abstract]
Sze WM, Shelley M, Held I, et al.: Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials. Cochrane Database Syst Rev (2): CD004721, 2004. [PUBMED Abstract]
Chow E, Zeng L, Salvo N, et al.: Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 24 (2): 112-24, 2012. [PUBMED Abstract]
van der Linden YM, Lok JJ, Steenland E, et al.: Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys 59 (2): 528-37, 2004. [PUBMED Abstract]
van der Linden YM, Steenland E, van Houwelingen HC, et al.: Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study. Radiother Oncol 78 (3): 245-53, 2006. [PUBMED Abstract]
Wong E, Hoskin P, Bedard G, et al.: Re-irradiation for painful bone metastases - a systematic review. Radiother Oncol 110 (1): 61-70, 2014. [PUBMED Abstract]
Chow R, Ding K, Ganesh V, et al.: Gender and age make no difference in the re-irradiation of painful bone metastases: A secondary analysis of the NCIC CTG SC.20 randomized trial. Radiother Oncol 126 (3): 541-546, 2018. [PUBMED Abstract]
Chow E, van der Linden YM, Roos D, et al.: Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 15 (2): 164-71, 2014. [PUBMED Abstract]
Chow E, Meyer RM, Ding K, et al.: Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol 16 (15): 1463-72, 2015. [PUBMED Abstract]
Serafini AN, Houston SJ, Resche I, et al.: Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol 16 (4): 1574-81, 1998. [PUBMED Abstract]
Sartor O, Reid RH, Bushnell DL, et al.: Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer 109 (3): 637-43, 2007. [PUBMED Abstract]
Resche I, Chatal JF, Pecking A, et al.: A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer 33 (10): 1583-91, 1997. [PUBMED Abstract]
Parker C, Nilsson S, Heinrich D, et al.: Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369 (3): 213-23, 2013. [PUBMED Abstract]
Bloch R: Rehabilitation medicine approach to cancer pain. Cancer Invest 22 (6): 944-8, 2004. [PUBMED Abstract]
Richardson MA, Sanders T, Palmer JL, et al.: Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol 18 (13): 2505-14, 2000. [PUBMED Abstract]
Bardia A, Barton DL, Prokop LJ, et al.: Efficacy of complementary and alternative medicine therapies in relieving cancer pain: a systematic review. J Clin Oncol 24 (34): 5457-64, 2006. [PUBMED Abstract]