Is pain or dependency driving elevated opioid use among long-term cancer survivors?


Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

Dr. Walter M. Stadler, director of the genitourinary program at the University of Chicago's Cancer Research Center.

Dr. Walter M. Stadler

“If you see these differences in opiate prescribing, is that because they are having pain, and more pain than we recognized in the past, or is this due to inappropriate long-term prescribing in patients who essentially may not have that much more pain, but have become dependent on these drugs?” asked Dr. Stadler, director of the genitourinary program at the University of Chicago’s Cancer Research Center. “Either one is in essence a problem … but we don’t know what the underlying cause may be. We can’t tell that from this particular study,” said Dr. Stadler, who also serves as the hematology/oncology section chief at the university.

One opportunity to reassess which medications and treatment modalities are appropriate for the cancer survivor, said Dr. Stadler, is at the point of discharge from oncology care, which usually happens at about the 5-year mark for patients with no evidence of disease. Survivorship has received more attention since the 2005 Institute of Medicine report calling for increased attention to cancer survivors’ ongoing care. However, he said, “it’s not clear that we do a very good job in terms of educating either the patient or their primary care physician in regards to the kinds of things that we expect, the kinds of things that need to be done, or even a good summary of the therapy that was provided.”

There are resources that can help, he said. “That’s why organizations like [the American Society for Clinical Oncology] have put together some more formal survivorship plans that should be provided when patients are transitioned.”

The realities of clinical life can get in the way of implementation, though. Oncologists are already stretched thin, and most electronic health record systems don’t integrate well with survivorship documentation. Finding staff who can spend the time to gather and package all the necessary information can also be a problem: “People are expensive, and none of us have extra cash lying around,” said Dr. Stadler.

Still, he said, “like a lot of good papers, this raises some issues and areas for further investigation.” First, he said, physicians must assess whether cancer survivors are having chronic pain, and then sort things out from there. “What are the pain syndromes – and what are we doing about them? – because it’s not something that’s been well addressed.”

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Dr. Larissa Nekhlyudov of the Dana-Farber Cancer Institute pediatric cancer survivorship clinic, Brigham & Women’s Hospital, and Harvard Medical School, Boston.

Dr. Larissa Nekhlyudov

In her roles as a clinician at the Dana-Farber Cancer Institute pediatric cancer survivorship clinic, as a primary care provider at Brigham & Women’s Hospital, and in teaching and research at Harvard Medical School, Boston, , she said she appreciates and emphasizes the heterogeneity of the survivor experience. Though some survivors may be relatively symptom free after treatment, for some, both physical and psychological effects may linger for a lifetime, she said, adding that she was not particularly surprised by the increased opioid-prescribing rates found in the recent study.

It’s reasonable to think that there might be an increased risk for chronic pain syndromes in some of the types of cancer in which elevated opioid prescribing rates were seen, said Dr. Nekhlyudov. “Maybe this is okay.

“Pain in cancer survivors is so multidimensional that it’s quite possible that some of these cancer survivors – gynecologic, lung, other gastrointestinal, genitourinary – might have peripheral neuropathy, adhesions, and so many potential late effects,” said Dr. Nekhlyudov. “However, narcotics are not necessarily the preferred and the only method to treat this pain,” she said, noting that optimal survivorship care might seek to transition these patients to nonopioid therapies or, at least, a multimodal approach.

When she’s wearing her survivorship care hat, said Dr. Nekhlyudov, managing pain medication isn’t always at the top of the to-do list in an office visit. “It’s certainly not uncommon that patients will have a variety of pain issues. But in the survivorship domain, I think that we don’t take the role of managing their pain medications; that piece belongs, really, to their primary care provider,” she said.

“In many ways, it’s difficult to distinguish how much of their pain is related to their cancer, versus not, and figuring out alternatives,” said Dr. Nekhlyudov, applauding the authors’ recognition of the need for a multimodal approach in cancer survivors with pain. However, she said, “that sounds really great on paper, but it’s really not readily available.”

Even in the resource-rich greater Boston area where she practices, said Dr. Nekhlyudov, “it’s very difficult for cancer patients – and noncancer patients – to get hooked into a multidisciplinary, holistic program for pain.”

Although the long-term perspective is helpful, Dr. Nekhlyudov hopes for research that can help identify at what point, and by whom, the opioids were initiated in the cancer survivor population. “What is their trajectory from the time of diagnosis? Are these patients who are started on narcotics during their cancer treatment, and then continue on forever, or are some of these patients being started later, because of late effects?”

In any case, she said, “one of the key pieces is the ownership for this really belongs with both oncologists and the primary care providers.”

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

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