Background: The 10-year survival rate of patients with differentiated thyroid cancer exceeds 90%. These patients may be at elevated risk for secondary cancers.

Methods: The risk of non-thyroid second primary malignancies following differentiated thyroid cancer was determined in 30,278 patients diagnosed between 1973 and 2002 from centers participating in the National Cancer Institute's SEER 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 non-thyroid second primary malignancies, significantly more than that expected in the general population (observed/expected [O/E] = 1.09 95% 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% CI 1.07 – 1.33, AER = 11.8) as well as for unirradiated patients (O/E = 1.05, 95% CI 1.00 – 1.10, AER = 3.53). However, the increased risk was greater for the irradiated versus the unirradiated cohort (relative risk, RR = 1.16, 95% CI 1.05 – 1.27, p<0.05). Gender did not affect risk. The greatest risk of second primary cancers occurred within five years 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.