Research has shown that pain is among the most commonly experienced and feared aspects of a cancer diagnosis.1 It’s easy to understand why. In fact, cancer-related pain is so ubiquitous, between 20% and 50% of patients with early-stage cancer will experience pain,2 and up to 90% of patients with advanced cancer will develop severe pain.3 In addition, as many as half of all cancer survivors will continue to experience pain and functional limitations long after their treatment has ended.4
Cancer-related pain is a complex biological and psychosocial phenomenon. Although not completely understood, it is believed to be the result of processes that involve cross-talk between neoplastic cells and a patient’s immune, peripheral, and central nervous systems. However, the cancer itself is not the only cause of the problem. All modalities of cancer treatment, including surgery, chemotherapy, radiation therapy, transplantation, and immunotherapy, also have the potential to cause long-term chronic pain.
Although pain caused by acute inflammation usually responds well to nonsteroidal anti-inflammatory drugs, opioids, such as methadone, oxycodone, and hydrocodone, have long been the mainstay to effectively manage moderate-to-severe cancer-related pain. However, their use poses serious challenges. The potential for the development of opioid use disorder or addiction and common side effects such as constipation, drowsiness, and nausea; stigma surrounding opioid use; reimbursement issues; and patients’ fear of becoming addicted highlight the need for evidence-based strategies to help oncologists and palliative care providers mitigate the risk of development of opioid use disorder in their patients while successfully managing patients’ cancer-related pain.
In response to these concerns, in 2016, ASCO published a new guideline on chronic pain management in cancer survivors and updated it in 2022.5 The revised guideline provides recommendations by ASCO’s expert panel of reviewers based on the evidence found in 31 systematic reviews and 16 randomized controlled trials. The recommendations include the following:
Opioids should be offered to patients with moderate-to-severe pain related to cancer or active cancer treatment unless contraindicated.
Opioids should be initiated as needed at the lowest possible dose to achieve acceptable analgesia and patient goals, with early assessment and frequent titration.
For patients with a history of substance use disorder, clinicians should collaborate with palliative care, pain, and/or substance use disorder specialists to determine the optimal approach to pain management.
Adverse effects related to the use of opioids should be monitored, and solutions should be offered to prevent and manage these adverse effects.
Janet Ho, MD, MPH, FASAM, FAAHPM
To learn more about how oncologists and palliative care providers may safely balance the use of opioid therapy to relieve cancer-related pain while protecting patients from addiction, The ASCO Post talked with Janet Ho, MD, MPH, FASAM, FAAHPM, Associate Professor of Palliative Medicine at the University of California, San Francisco. Dr. Ho is also an addiction medicine specialist at Zuckerberg San Francisco General Hospital and Trauma Center.
Addressing the Problem of Long-Term Cancer-Related Pain
Please talk about how oncologists and palliative care physicians can address the chronic cancer-related pain patients experience and how the challenges of achieving effective pain relief can be overcome.
Chronic cancer pain is increasingly recognized as an entity that palliative care clinicians, oncologists, and primary care physicians have to manage. Decades ago, cancer-related pain was largely untreated or undertreated. That changed after palliative care became recognized as a subspecialty to improve the quality of life of patients with serious or life-threatening diseases, including cancer, and to help patients better tolerate cancer treatment.
In the past, clinicians tended not to worry about the dangers of prescribing opioids to patients with advanced cancer because many of these patients died within a short time. Now, with the advances in cancer treatment, patients with advanced disease are living much longer, and some are even cured of their cancer. And, in this setting, we’re realizing we cannot keep these patients on high doses of these medications indefinitely because of the high risk for adverse events, including potentially triggering a new opioid abuse disorder, a complicated dependence on the drug, or even an accidental overdose.
There is also increasing evidence that the higher the dose and the longer periods that patients are on these medications may also contribute to other detrimental effects in the survivorship population, including hormonal disruption, endocrine destruction, and immune suppression. Despite these risks, we know that a high percentage of cancer survivors continue to have moderate-to-severe cancer pain, even after the disease is stabilized, and we have to address this problem. We’re a little behind the gap in trying to figure out how best to provide better care for these patients.
Understanding the Biology of Chronic Cancer Pain
Please talk about the underlying mechanisms of pain in patients with cancer.
There are myriad ways cancer produces pain. There is guidance showing that some chronic pain is neuropathic, caused by a mass irritating the nerve, and we have neuropathic agents to reduce that type of pain. A tumor invading the bone will cause bony pain, which has an inflammatory component; in that case, patients might respond well to anti-inflammatory agents.
However, chronic cancer-related pain is often multidimensional, and, in addition to a physical component, it may include psychosocial, emotional, and spiritual aspects. Consequently, addressing chronic pain management often requires a multidisciplinary approach from experts across diverse medical fields, including medical oncology, radiation oncology, palliative care, and physiatry, as well as from psychiatry, psychology, social work, and chaplaincy.
There is a discussion now underway about whether chronic cancer-related pain is its own entity, differing from other types of chronic pain, and, therefore, it should be treated differently, or whether we should approach it as we do other chronic pain for which opioids are not first-line treatment. We need more research in this area to determine the exact underlying mechanisms of this type of pain and, more importantly, how best to treat it.
Balancing the Harms and Benefits of Opioid Use
According to the Centers for Disease Control and Prevention, from 1999 to 2019, nearly 500,000 people died of an overdose involving prescription and illicit opioids.6 How can palliative care providers balance opioid use to relieve cancer-related pain while protecting patients from addiction and death?
We’ve learned so much about the dangers of the long-term use of opioids, and prescribers have adjusted their practices accordingly. As a result, opioid prescriptions have decreased sharply over the past decades. But, at the same time, these medications are helpful in aggressively treating cancer-related pain and are widely accepted as a standard of care for cancer-related pain.
Before we start a patient on opioids to manage pain, we should first assess the patient’s level of symptom burden. The Edmonton Symptom Assessment System (https://albertametis.com/app/uploads/2022/01/ESAS-Tool_V4.pdf) is a reliable tool to assist palliative care physicians in determining and tracking a patient’s level of pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath. The information can then be used to start a discussion about how to manage the patient’s chronic pain in the context of overall levels of distress.
Janet L. Abrahm, MD, FACP, FAAHPM, FASCO
Dr. Abrahm is Professor of Medicine at Harvard Medical School and former Chief of the Division of Adult Palliative Care, Department of Supportive Oncology, Dana-Farber Cancer Institute, and Division of Palliative Medicine, Brigham and Women’s Hospital. Palliative Care in Oncology addresses the evolving needs of cancer survivors at various stages of their illness.
Oncologists and palliative care physicians should also institute an ongoing benefit/risk analysis to ensure that the opioid being prescribed is providing more benefit than harm. We also need to bring patients into this informed consent and decision-making process in the form of more disclosure about the benefits and risks of these medications, including their side effects and potential for the development of complicated dependence or addiction, as well as the process of tapering off these medications once treatment is completed. We then need to revisit these discussions on a regular basis.
Buprenorphine has emerged over the past several decades as a safer alternative in the effective management of moderate-to-severe chronic cancer-related pain than full-agonist opioids such as morphine, fentanyl, hydrocodone, and oxycodone, especially for patients who may need to be on a pain medication for a long time, are unable to taper off full-agonist opioids after active cancer treatment is completed, or may have a substance use disorder. I encourage oncologists and palliative care physicians to familiarize themselves with buprenorphine, a partial-agonist opioid, which should be considered a first-line opioid in this setting.
Predicting Opioid Addiction in Cancer Survivors
What are the predictive factors for opioid addiction in cancer survivors?
Research shows several factors are associated with the risk of persistent opioid therapy in this population, including younger age, unemployment at the time of the cancer diagnosis, lower median income, increased comorbidity, and current or prior tobacco use. Alcohol as well as depression and a history of chronic opioid use are also factors.7
Similarly, patients with psychiatric conditions (including bipolar disorder, schizophrenia, obsessive-compulsive disease, and attention deficit disorder) are also at higher risk for developing an opioid use disorder. In addition, there is a genetic component that may predispose a person to having a substance use disorder after exposure to that substance, including opioids prescribed for cancer pain.
Before prescribing opioids to cancer survivors for pain management, physicians should use a screening tool to help identify those who may have concerning substance use or a current substance use disorder or who may be at higher risk for developing an opioid use disorder to prevent related health consequences, accidents, and injuries. The National Institute on Drug Abuse has a useful Opioid Risk Tool for pain management (https://nida.nih.gov/nidamed-medical-health-professionals/screening-tools-resources/opioid-risk-tool-oud-ort-oud). Another is the Screening, Brief Intervention, and Referral to Treatment (www.samhsa.gov/substance-use/treatment/sbirt).
Although opioid risk tools may help to guide clinicians on risk stratification, none have been validated for use in cancer survivors, nor can they diagnose substance use disorder or fully identify who is likely to develop an opioid use disorder. Still, they may be helpful in providing information on substance use history, identifying the most appropriate opioid therapy for individual patients, and in normalizing and initiating a nonjudgmental conversation with patients about substance use.
DISCLOSURE: Dr. Ho reported no conflicts of interest.
REFERENCES
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2. Fischer DJ, Villines D, Kim YO, et al: Anxiety, depression, and pain: Differences by primary cancer. Support Care Cancer 18:801-810, 2010.
3. Falk S, Dickenson AH: Pain and nociception: Mechanisms of cancer-induced bone pain. J Clin Oncol 32:1647-1654, 2014.
4. Harrington CB, Hansen JA, Moskowitz M, et al: It’s not over when it’s over: Long-term symptoms in cancer survivors—A systematic review. Int J Psychiatry Med 40:163-181, 2010.
5. Paice JA, Bohlke K, Barton D, et al: Use of opioids for adults with pain from cancer or cancer treatment: ASCO Guideline. J Clin Oncol 41:914-930, 2023.
6. Centers for Disease Control and Prevention: Uncovering the opioid epidemic. Available at www.cdc.gov/museum/pdf/cdcm-pha-stem-uncovering-the-opioid-epidemic-lesson.pdf. Accessed August 6, 2025.
7. Jones KF, Fu MR, Merlin JS, et al: Exploring factors associated with long-term opioid therapy in cancer survivors: An integrative review. J Pain Symptom Manage 61:395-415, 2021.