Background: A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. Methods: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. Results: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediaterisk, and 68% of the high-risk patients ( p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. Conclusions: Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

Recent studies have confirmed that radioactive iodine therapy after recombinant human TSH (rhTSH) stimulation effectively ablates the normal thyroid remnant. However, no published study has determined the effectiveness of rhTSH preparations on the important endpoint of disease recurrence. Methods: Disease recurrence was retrospectively assessed a median of 2.5 y after radioiodine remnant ablation (RRA) in 394 consecutive thyroid cancer patients (93% papillary, 71% female, 47 6 15 y old [mean 6 SD], median 131 I dose of 3,996 MBq [108 mCi]). Results: Similar rates of clinically evident disease recurrence (4% rhTSH vs. 7% thyroid hormone withdrawal [THW], P 5 not statistically significant) and residual thyroid bed uptake without other evidence of persistent disease (4% rhTSH vs. 7% THW, P 5 not statistically significant) were seen in the 320 patients undergoing rhTSH-assisted RRA and the 74 patients prepared for RRA by THW. When the definition of no clinical evidence of disease included a suppressed thyroglobulin level of less than 1 ng/ mL and a stimulated thyroglobulin level of less than 2 ng/mL, rhTSH-assisted RRA was associated with significantly higher rates of no clinical evidence of disease (74% rhTSH vs. 55% THW, P 5 0.02) and significantly lower rates of persistent disease (19% rhTSH vs. 32% THW, P 5 0.02) than was RRA after THW. Patients selected for rhTSH-assisted RRA were older (48 6 15 vs. 44 6 15 y, P 5 0.03) and received a slightly higher administered activity of 131 I (median,4,033 MBq [109 mCi] vs. 3,811 MBq [103 mCi], P 5 0.01) but did not differ with respect to sex, histology, disease stage, or mean time to recurrence (19 6 9 mo for rhTSH vs. 20 6 16 mo for THW). Conclusion: rhTSHassisted RRA is associated with rates of clinically evident disease recurrence and persistent uptake in the thyroid bed that are similar to those for traditional THW.

In patients selected for continued observation, serum Tg levels often continue to decline for several years after total Tx and RAI-RA. While a 6-12-month assessment of the response to initial therapy is useful in patient management, strong consideration should be given to continued observation without additional therapy in patients with well-differentiated thyroid cancer who have 6-month suppressed serum Tg values of 1-5 ng/mL without a structurally identifiable disease.

Preparation with either rhTSH or THW in this retrospective study appears to have similar therapeutic (tumoricidal) effects on small volume RAI-avid metastatic disease incidentally discovered at the time of ablation in both locoregional lymph nodes and pulmonary parenchyma.

In otherwise, healthy patients with differentiated thyroid cancer, significant weight gain occurred during the 3-5 years of follow-up despite ongoing thyrotropin suppression. The data suggest that mild iatrogenic hyperthyroidism does not promote weight loss or prevent ageing-related weight gain. Greater weight gain was seen in patients prepared for radioactive remnant ablation with THW than with rhTSH.