Locoregional recurrence of differentiated thyroid cancer has a negative impact on overall and cause-specific survival in patients age 65 and older, according to an evaluation of Surveillance, Epidemiology, and End Results (SEER) data published in conjunction with the American Society of Clinical Oncology Annual Meeting (Abstract e17003).
While treating all thyroid cancer may not be advantageous, this study found that a cohort of older patients with locoregional recurrence of differentiated thyroid have a greater chance of dying, explained the senior author, Jonathan J. Beitler, MD, MBA, Professor of Radiation Oncology, Otolaryngology and Hematology/Medical Oncology at Winship Cancer Institute of Emory University.
He said that while the results were expected, they are not currently reflected in the literature: “A lot of thyroid cancer is like prostate cancer in that people die with it, not of it,” he explained.
Asked for his opinion for this article, Dennis H. Kraus, MD, Director of the Center for Head & Neck Oncology at New York Head & Neck Institute, North Shore-LIJ Cancer Institute, said that women over age 55 and men over 45 are currently categorized as being at intermediate to high risk for recurrence and that because this study evaluated individuals 65 and older, patients would be expected to have a worse prognosis and a higher risk of local or regional disease recurrence.
Added Bryan McIver, MD, an endocrinologist at Moffitt Cancer Center: “I think these are the kinds of data we should pay close attention to. The pendulum of perception during the last 30 years has swung between locoregional recurrence being a harbinger of death, to that such recurrences are a nuisance but not life-threatening. This study allows physicians to focus on a high-risk group.”
For the study, Beitler and his colleagues evaluated the SEER database and linked it to Medicare claim files to identify patients age 65 and older diagnosed with primary non-metastatic differentiated thyroid cancer between 1991 and 2007. A total of 6,235 eligible patients were identified, including 214 with recurrent disease, defined as undergoing nodal dissection as salvage therapy more than six months after initial diagnosis. The overall survival and cause-specific survival of these patients were then compared with those of 1,070 matched controls with nonrecurrent disease.
Individuals with recurrent disease were significantly more likely to be non-Caucasian and male and to have more advanced disease at presentation. Five-year overall and cause-specific survival rates were 55.1 and 64.4 percent, respectively, in patients with recurrent disease. These rates were 72.1 and 92.9 percent, respectively, in the matched controls.
Multivariate analysis assessing age, stage, race, and gender as covariables found that recurrent disease was independently and significantly associated with lower five-year overall survival and cause-specific survival.
Based on this study, neck dissection for salvage treatment in this population “may not be sufficient,” Beitler said. “There were excess deaths, and the number of excess deaths was statistically significant.” And while neck dissection is not completely successful, whether anything works better than surgery alone for salvage is unknown, he added.
Anurag K. Singh, MD, Professor of Oncology and Director of Radiation Research at Roswell Park Cancer Institute and Professor of Medicine and Radiation Medicine Residency Program Director at the University at Buffalo School of Medicine, said the study is well designed and well analyzed. A limitation, though, perhaps because the data were not available in SEER, is that there is no indication of the eventual mode of death—for example, was death due to the local recurrence, to distant disease, or other causes?
Another drawback, McIver said, is that SEER data can be somewhat suspect because the pathology of thyroid tumors has not been reviewed in a central location and may not apply across the board. Notably, there is some confusion between follicular and papillary thyroid cancers, he said. The data are also retrospective, which can introduce bias.
More Aggressive Treatment Considered
Still, he said, despite any limitations, the study raises the question of whether older patients need more aggressive intervention. For example, prior studies have demonstrated that use of external-beam radiation therapy (EBRT) in well-differentiated thyroid cancer patients who have already undergone surgery and RAI might reduce recurrence. However, patients typically aren't even offered EBRT due to the associated high morbidity and are instead advised to have neck dissection as rescue therapy.
“Maybe we need to be more proactive and be willing to offer treatment like EBRT, at least to high-risk, older patients,” McIver said, noting that this, though, remains a hypothesis that needs to be studied.
Kraus said that some of these older patients with aggressive histology or with disease outside of the thyroid may need to be treated more assertively with surgery, and may also need more comprehensive imaging of the neck, followed by upfront resection of any nodal disease.
Beitler noted that although it is not demonstrated in the data in the abstract, most of this population would have received RAI and synthroid, but this approach does not appear to have been successful. Tumors become less sensitive to RAI over time and patients can tolerate only a certain amount of this treatment.
RAI as adjuvant therapy is a “double-edged sword,” Kraus said. While this group of older patients needs more treatment, RAI is often less effective for thyroid cancer in this population when compared with the results in younger patients.
Adjuvant therapy to the thyroid bed often carries acute and long-term morbidity that has to be balanced against the potential benefits, Singh said. “It remains to be seen whether adjuvant therapy in this cohort of patients would actually improve survival.”
Further research needs to determine whether adjuvant systemic treatment or locoregional treatment is what this patient population should be getting, Beitler said. Additionally, researchers need to assess whether failures after neck dissection are in the neck or distantly. A prospective study to see what additional treatments might improve results is warranted.
There are very few randomized trials in thyroid cancer, Beitler added. “It was once such a rare bird that it was thought it would be impossible to mount these studies, but thyroid cancer is more common now.” The disease also has a long natural history, so being patient with long-term follow-up is an important consideration.
“What's exciting is that there are new small molecule drugs and agents,” Kraus said. “In theory, they may cause poorly differentiated cancers to become well differentiated, which improves RAI uptake—this is the holy grail.”