Second Primary Cancer in Patients with Papillary Thyroid Carcinoma

Discussion

Treatment of DTC includes surgery, with total thyroidectomy in most cases, ¹³¹I_Na ablation of remnant thyroid tissue, and long-term thyrotropin-suppressive therapy with supra-physiological doses of levothyroxine (8). DTC has a relatively benign prognosis, and the 10-year survival rate is close to 95%. Several reports have shown that patients with DTC are at elevated risk for SPC. Non-thyroid malignancy can occur before, after, or at the same time as DTC.

The risk of non-thyroid malignancy in survivors of DTC has been extensively studied. Ronckers et al. (3) reported an 11% elevated risk compared to that in the general population. Sandeep et al. (4), in a multinational study with >30,000 patients with DTC, found that the risk of SPC was 1.31. A systematic review and meta-analysis performed by Subramanian et al. (5) in 2007 concluded that the standardised incidence ratio of SPC in thyroid cancer survivors was 1.20 (95% confidence interval, 1.17-1.24). In a multinational European cohort, the increased risk of SPC was quantified as >27% (9). Other studies with smaller case numbers have confirmed these data. However, whether the risk of SPC after DTC is the consequence of radioiodine treatment, as has been suggested, remains controversial. Fallahi et al. (10) reported that a cumulative dose of ¹³¹I_Na of >1.08 Ci was associated with an increase in SPC. Ronckers et al. (3) also found a two-fold increased risk of additional cancer in organs that concentrate ¹³¹I_Na among patients with thyroid carcinoma. However, other authors have not found such an association. For example, Bhattacharyya and Chien (11) compared patients with DTC treated with or without ¹³¹I_Na and did not find any difference in the risk of SPC. In addition, Berthe et al. (12) and Verkooijen et al. (13) did not find any causal relation with iodine therapy.

Conversely, the risk of DTC after non-thyroid primary malignancy has also been demonstrated. In the study of Ronckers et al. (3), the overall risk was 42% higher than expected. In the study of Sandeep et al. (4), there was an increased risk of thyroid cancer after many types of primary malignancies. Thyroid cancer was the second most prevalent, after primary melanoma, in a cohort of more than 70,000 patients with invasive melanoma (14).

Finally, DTC can be concurrently diagnosed with another primary cancer. Synchronous malignancies are currently defined as those diagnosed within the same year. Ronckers et al. (3) reported that for many types of cancer, the risk of DTC was stronger in the first year after, or before, the other malignancy. Sandeep et al. (4) found that for all cancers combined and for several specific malignancies, a significant risk of SPC was highest within a year of diagnosis of the primary neoplasm. The results of the present study are in agreement with the findings of Ömur et al. (6), who reported that a third of patients with multiple primary tumours had concurrent DTC and SPC. Moreover, Lang et al. (7) have reported that patients with synchronous second malignancy had more advanced DTC and were more likely to die from thyroid cancer than those with metachronous SPC. In this regard, we report that PTC in the synchronous tumour group was larger than in the metachronous group. Hence, the number of papillary microcarcinomas was higher in patients with non-synchronous than in those with synchronous tumours. All these findings support the idea that far from being a detection bias motivated by close medical surveillance, a common risk factor or a temporary predisposition may play a role in the concurrence of both tumours.

In conclusion, patients with DTC are at elevated risk for SPC. In a third of cases, both neoplasms were diagnosed within the same year. Additional primary tumours were most frequent in male and older patients. Breast cancer is the most frequent tumour associated with thyroid carcinoma. Finally, PTC in patients with synchronous tumours is larger than in those with metachronous tumours.