Rising incidence of second cancers in patients with low-risk (T1N0) thyroid cancer who receive radioactive iodine therapy

Abstract

Background: American Thyroid Association guidelines currently recommend the selective use of radioactive iodine (RAI) therapy in patients with well differentiated thyroid cancer (WDTC). Despite these guidelines, RAI ablation has been used routinely in all but the very lowest risk patients with thyroid cancer over the last 30 years. The objective of this study was to evaluate patterns of RAI use and elevated risk of secondary primary malignancies (SPM) in patients with low-risk (T1N0) WDTC.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze trends in RAI use over time in the United States. To determine the excess risk of SPM, the standardized incidence ratio (SIR) and excess absolute risk (EAR) of various cancers were calculated in the 2 cohorts. Between 1973 and 2007, 37,176 patients with WDTC were followed in the SEER Program, equating to 408,750 person-years at risk (PYR). In total, 14,589 patients received RAI, and SPMs were observed in 3223 patients.

Results: During the study period, the rate of RAI use in patients with low-risk (T1N0) WDTC increased from 3.3% to 38.1%. For low-risk patients, the SIR of SPM was 1.21 (95% confidence interval [CI], 0.93-1.54), and the EAR was 4.6 excess cases per 10,000 PYR. SPM with significantly elevated risk because of RAI were salivary gland malignancies (SIR = 11.13; 95% CI, 1.35-40.2) and leukemia (SIR = 5.68; 95% CI, 2.09-12.37). The excess risk of leukemia was significantly greater in patients aged <45 years (SIR = 5.32; 95% CI, 2.75-9.30) compared with the excess risk in older patients (SIR = 2.26; 95% CI, 1.43-3.39).

Conclusions: The increased risk of a SPM in patients with low-risk (T1N0) WDTC, along with a lack of data demonstrating improved survival outcomes with adjuvant RAI, provide a compelling argument in favor of rationing the use of RAI in this patient population.

Figure 1

The incidence of well differentiated thyroid cancer (WDTC) over time is illustrated for all patients and for low-risk patients.

Figure 2

The proportion of patients receiving radioactive iodine (RAI) treatment in illustrated for all patients and for patients aged <45 years with low-risk well differentiated thyroid cancer (WDTC) (left; y-axis), and overall survival is illustrated (right; y-axis) for the period from 1973 and 2006. Tumor size was recorded after 1983. For the purposes of this illustration, before 1983, low-risk disease was defined as intrathyroid N0M0 tumors; after 1983, low-risk was defined as T1N0M0 tumors.

Figure 3

Increasing second primary malignancy (SPM) rates with time for all malignancies and leukemias are illustrated in patients with well differentiated thyroid cancer (WDTC). The horizontal line indicates a standardized incidence ratio (SIR) of 1.0; error bars indicate 95% confidence intervals.