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Active surveillance for small papillary thyroid cancers should be used with caution
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Active surveillance without surgery may not be the most appropriate approach for patients with small papillary thyroid cancers, according to a population-based study.
Thyroid cancer is the most common endocrine malignancy, accounting for 3.8% of all new cancer diagnoses, according to study background information. It is the fifth most common cancer diagnosed in women, and its age-adjusted and sex-adjusted incidence has increased faster than any malignancy in the past decade.
Since 2004, incidence has increased by 5.6% in men and 7% among women; however, men tend to have a more advanced stage of thyroid cancer at an older age, and they typically demonstrate shorter DFS and higher mortality.
Yet, some centers have advocated for patients with small papillary thyroid cancer to follow a course of active surveillance in lieu of surgery.
Naris Nilubol, MD, FACS, and Electron Kebebew, MD, FACS, both of the endocrine oncology branch at the National Cancer Institute, analyzed the impact of small papillary thyroid (tumors ≤ 2 cm in dimension) on thyroid cancer-related mortality.
Researchers used the SEER database to identify 61,523 patients from 17 registries who had histologically confirmed thyroid cancer of follicular cell origin between 1988 and 2007.
From that cohort, 1,753 patients (2.8%) died of thyroid cancer. Of those who died, more than one-third (38%) had papillary thyroid cancer, and 12.3% had papillary thyroid cancers ≤2 cm.
Among all patients with papillary thyroid cancers ≤2 cm, thyroid cancer mortality was significantly higher among men (30% vs. 17%: P<.01); those aged ≥45 years (92% vs. 52%; P<.01); those whose tumors measured larger than 1 cm (59% vs. 46%; P<.01); and those who demonstrated extrathyroid extension (41% vs. 11%; P<.01). Mortality also was higher among patients who developed lymph node metastases (77% vs. 28%; P<.01) and those who developed distant metastases (31% vs. 1%; P<.01).
Multivariate analysis showed several factors were independent prognostic factors for thyroid cancer-related mortality among patients with papillary thyroid cancer ≤2 cm. Those factors included age ≥45 years (HR=12.2; P<.01), extrathyroid extension (HR=2.8; P<.01), lymph node metastases (HR=5.4; P<.01), distant metastases (HR=6.4; P<.01), undergoing less than thyroid lobectomy (HR=13.7; P=.01), and receipt of either external radiotherapy (HR=8.9; P<.01) or the combination of external radiotherapy and radioisotopes (HR=8.1; P<.01).
“The current study demonstrates that 12.3% of deaths related to thyroid cancer occurred in patients with papillary thyroid cancers ≤2 cm who underwent thyroidectomy,” Nilubol and Kebebew wrote. “Given the rise in the incidence of small thyroid cancers, nonoperative management for this growing population of patients should be used with caution. Patients aged ≥45 years or men of any age with a papillary thyroid cancer ≤2 cm should undergo at least thyroid lobectomy.”
Disclosure: The study was supported by the Intramural Research Program of the Center for Cancer Research, the NCI and the NIH. The researchers report no relevant financial disclosures.
Perspective
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Marita S. Teng, MD, FACS
“Active surveillance” is the term used to describe the close observation of small-volume, favorable-risk cancer. A patient with prostate cancer who fits into this category has disease that is highly unlikely to become clinically apparent over the course of his or her lifetime. In theory, the small percentage of “low-risk” patients who end up demonstrating more aggressive disease are identified through active surveillance, and they are then treated effectively.
Is this concept applicable to thyroid cancer? Thyroid cancer incidence has increased more than 6% per year since 2004. This is an alarming statistic, but it is one that experts agree is due to improved detection methods. Thyroid nodules — and, consequently, small papillary thyroid cancers (PTC) — are often discovered incidentally on radiologic studies ordered for other purposes. This phenomenon of increased detection/incidence has the positive effect of identifying patients at an earlier, more curable stage, but also potentially the negative effect of overtreating non-life threatening disease.
Numerous authors have previously advocated close observation of “micro” papillary thyroid cancers measuring less than 1 cm. The paper by Naris Nilubol, MD, FACS, and Electron Kebebew, MD, FACS, attempts to elucidate whether this concept can or should be applied to “small” papillary thyroid cancers (less than 2 cm). Their data review demonstrates that over a 20-year period (1987 to 2007), 12.3% of thyroid cancer-related deaths were attributable to these small PTCs. The only statistically significant independent predictor of mortality in this group was age ≥45 years. However, male patients — owing to their higher rates of extrathyroidal extension, as well as regional and distant metastases — also demonstrated higher mortality. Given that SEER database review has the limitation of tracking mostly patients who have undergone surgery, the figure of 12.3% thyroid cancer-related deaths occurring in patients with small tumors is even more concerning, as these patients were almost all treated, not just observed.
Based on these data, nonoperative management of small papillary thyroid cancers should be used cautiously, especially in patients who are male or aged ≥45 years. Many recent scientific strides have involved genetic testing of thyroid nodule needle biopsy specimens. Using this type of molecular information, we should be hopeful that — in the near future — appropriate treatment of small thyroid cancers will be more individualized, based on tumor biology and not size alone.
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