The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer

Background: The 10-yr survival rate of patients with differentiated thyroid cancer exceeds 90%. These patients may be at elevated risk for secondary cancers. Methods: The risk of nonthyroid second primary malignancies after differentiated thyroid cancer was determined in 30,278 patients diagnosed between 1973 and 2002 from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Median follow-up was 103 months (range, 2-359 months). Risk was further assessed for the addition of radioisotope therapy, gender, latency to development of secondary cancer, and age at thyroid cancer diagnosis. Results: There were 2158 patients who developed a total of 2338 nonthyroid second primary malignancies, significantly more than that expected in the general population [observed/expected (O/E) = 1.09; 95% confidence interval (CI), 1.05-1.14; P < 0.05; absolute excess risk per 10,000 person-years (AER) = 6.39]. A significantly greater risk of second primary malignancies over that expected in the general population was for patients treated with radioisotopes (O/E = 1.20; 95% Cl, 1.07-1.33; AER = 11.8) as well as for unirradiated patients (O/E = 1.05; 95% Cl, 1.00-1.10; AER = 3.53). However, the increased risk was greater for the irradiated vs. the unirradiated cohort (relative risk = 1.16; 95% Cl, 1.05-1.27; P < 0.05). Gender did not affect risk. The greatest risk of second primary cancers occurred within 5 yr of diagnosis and was elevated for younger patients. Conclusions: The overall risk of second primary malignancies is increased for thyroid cancer survivors and varies by radioisotope therapy, latency, and age at diagnosis.