A study in a recent issue of Endocrine Reviews addresses the myriad controversies surrounding the treatment of low-risk differentiated thyroid cancer. While every facet of patient care has its own debates, education and more in-depth studies are key to finding common ground.
Last August, a paper appeared in Endocrine Reviews aiming to address the controversies swirling around the management of low-risk differentiated thyroid cancer (DTC), since these controversies stem from differing views on how to handle these patients, which puts these patients at risk of being under- or over-treated.
The paper, “Controversies in the Management of Low-Risk Differentiated Thyroid Cancer,” by Megan R. Haymart, MD, of the University of Michigan, et al., points out that the controversies extend across all aspects of management, from surgery to use of radioiodine to long-term surveillance, and prior work has shown that there is marked variation in the management of low-risk DTC. Preferences for treatment can vary from physician to physician and from patient to patient. The paper was an Editor’s Choice for that month, since bringing awareness to these controversies and then acting to mitigate them will reduce patient harm.
According to Leonard Wartofsky, MD, MACP, professor of medicine at Georgetown University and editor-in-chief of Endocrine Reviews, these controversies have come to greater attention since the American Thyroid Association released its most recent guidelines, published last year in Thyroid. “There were changes, really, in every step of the way in the management of patients with thyroid nodules and thyroid cancer that were counter to past practice,” he says.
Low-risk DTC patients have excellent prognoses, and intensive treatment may put them at increased risk for harm. Intensive surgical treatment can be associated with increased risks of hypoparathyroidism and vocal fold paralysis. Treatment with radioactive iodine can be associated with salivary gland or lacrimal duct damage. “It is important for patients to receive an intensity of treatment that fits the severity of their disease,” Haymart says. “Otherwise, the risks of harms may outweigh treatment benefits.”
Unending Controversies
And it doesn’t help that, again, these controversies are spread across every aspect of the care of patients with low-risk DTC. There’s disagreement on when to use active surveillance (no surgery but close follow-up) versus lobectomy versus total thyroidectomy. Haymart and her team point to studies from Japan by Ito et al., that showed if patients have very small, lowrisk tumors, they may not need surgery at all. “This, of course, is a bit of a shock to surgeons and practitioners out there who have been taught for years you have to do a total thyroidectomy when there’s thyroid cancer,” Wartofsky says. “We’re talking about patients who have a nodule, get it biopsied, and it is cancer, but we don’t operate. We follow these patients, and should the nodule grow, or should it look like it spreads to lymph nodes, then they certainly need to be operated on.”
Then there’s disagreement on when and whom to treat with radioactive iodine and thyroid hormone suppression. “Thyroid hormone suppression may not be necessary in our lowest risk patients,” Haymart says. “However, there is evidence that suppressive doses of thyroid hormone are still used for some patients with low-risk disease. Finally, since data on optimal long-term surveillance is sparse, optimal length and interval of long-term surveillance for low-risk differentiated thyroid cancer remains unknown.
“This lack of physician consensus results in wide variation in patient care. There is a need to reduce this variation in care through rigorous study design, dissemination of study results, and physician and patient education.”
“This lack of physician consensus results in wide variation in patient care. There is a need to reduce this variation in care through rigorous study design, dissemination of study results, and physician and patient education.” — Megan R. Haymart, MD, assistant professor of medicine, the University of Michigan, Ann Arbor
Underpowered Studies
And that’s one big factor driving these controversies, that many of the currently available studies are limited by small sample sizes and short follow-up. Haymart says that even though there are projected to be more than 50,000 new cases of thyroid cancer in 2017, it’s still a relatively rare disease. And many patients do well when treated; the incidence of recurrence and mortality is low. “Many of the current published studies are from single institutions. The combination of the relatively low prevalence of thyroid cancer combined with the low event rate make many of these studies underpowered to study outcomes most important to patients and their providers,” she says. “Population-based cancer registries such as Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database do have large enough patient cohorts but some relevant cancer details such as tumor marker level, result of I-131 scan, etc., are not available in these large national registries.”
“This is a challenge and an opportunity for researchers interested in thyroid cancer outcomes,” Haymart continues. “Researchers will have to think creatively and collaboratively to address the limitations.”
Things are starting to slowly smooth out, but that means more studies are needed. Haymart says that the new National Comprehensive Cancer Network and American Thyroid Association guidelines are a step in the right direction. “Dissemination of relevant study results is also important. Ultimately, physician and patient education are key,” she says.
Complex Decision Tree
But all of these controversies point back to the importance of shared decision making and personalized medicine, spending more time with each patient to craft individualized treatment plans. “Treatment intensity should be tailored to the severity of the disease,” Haymart says.
Wartofsky says it’s a complex decision tree when personalizing these approaches to therapy. How big was the tumor? Did it spread to the lymph nodes? Was there local invasion? How old is the patient? “All of those things affect staging,” he says. “Based on the staging, we make those decisions.”
Anxiety can factor into the decision-making process as well. Some patients may balk when they’re told they have cancer but there’s no need to operate. Of course, patients aren’t privy to all of the data indicating that the majority of well-differentiated papillary cancer patients do well, and the cure rate is higher than 95%. “They think cancer is cancer, and they know people who have died of cancer,” Wartofsky says. “Of course it provokes a lot of anxiety.”
He says he has patients who insist on follow-up appointments to make sure there has been no recurrence, even though Wartofsky and his colleagues have assured these patients there is no sign of cancer left and they have indeed been cured. “We all differ in the degree of anxiety generated and how we deal with uncertainty,” he says.
“Cancer-related worry is an important problem for many of our patients,” Haymart says. “Education, access to support groups, access to counseling when needed, and future studies addressing worry and the role of worry-support tools are necessary to improve patient worry.”
Lack of Consensus
In the future, Wartofsky says, the endocrinologists studying and treating these tumors will be able to make better determinations about treatment, since they’ll be able to conduct mutational and molecular analyses, leading to fewer controversies. “There’s certain abnormalities that are known to be more aggressive, so we will treat those tumors more aggressively,” he says. “The ones that are minor mutations we may be able to clinically follow safely without progressive intervention.”
Haymart and her team have National Institutes of Health funding to study thyroid cancer treatment decision making. “With the use of survey studies linked to SEER data, we hope to obtain more information on how treatment decisions are being made and to identify the reasons for more versus less intensive treatment,” she says.
But for now, controversies remain over optimal treatment of low-risk DTC. “This lack of physician consensus results in wide variation in patient care,” Haymart says. “There is a need to reduce this variation in care through rigorous study design, dissemination of study results, and physician and patient education.”
“I highly recommend clinicians who treat patients with thyroid cancer to read [‘Controversies in the Management of Low-Risk Differentiated Thyroid Cancer’],” Wartofsky says. “It’s very well done. I think that maybe in the future, some of these management controversies will be cleared up when we have more information about the molecular nature of these tumors.”
— Bagley is the senior editor of Endocrine News. He wrote about the latest developments in endocrine technology in the December issue.
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