Dynamic Risk Assessment Using Unstimulated Serum Thyroglobulin Level and Thyroglobulin Doubling Rate after Total...

Background: Thyroglobulin (Tg), stimulated or unstimulated by recombinant human thyrotropin (TSH), is a static marker of recurrent or persistent disease, and the Tg-doubling rate (Tg-DR) is a dynamic prognostic factor. This study evaluated the prognostic value of an unstimulated Tg (uTg) and Tg-DR papillary thyroid carcinoma (PTC). Methods: This retrospective study included 1818 Tg antibody (Tg-Ab)-negative patients who underwent curative intent total thyroidectomy for PTC without distant metastasis. The uTg was measured 1-3 months post-surgery under TSH suppression (<0.1 mIU/mL). We calculated the Tg-DR for patients, of whom postoperative Tg levels could be measured three or more times under TSH suppression. Results: Eighty-eight (4.8%) and 32 (1.8%) patients had respective local and distant recurrences (median follow-up period, 7.2 years; 25th percentile 4.7 years, 75th percentile 9.8 years). Of 1818 patients, 131 had a uTg ≥3 ng/mL and were more likely to display local and distant recurrences in univariate and multivariable analyses (p < 0.001). We divided 1212 patients with no adjuvant radioactive iodine treatment, of whom uTg and Tg-DR data were available, into four categories A, uTg ≥3 ng/mL and Tg-DR ≥0.33/year; B, uTg <3 ng/mL and Tg-DR ≥0.33/year; C, uTg ≥3 ng/mL and Tg-DR <0.33/year; and D, uTg <3 ng/mL and Tg-DR <0.33/year. The lymph node recurrence-free survival rate was significantly worse from category A to D (A vs. B, p < 0.001, hazard ratio or HR [CI]: 5.083 [1.994-12.955]; B vs. C, p = 0.001, HR [CI]: 2.654 [1.462-4.824]; C vs. D, p < 0.001, HR [CI]: 27.420 [15.100-4.980]). The distant recurrence-free survival rate (DR-FS) of category B did not differ from that of category C (p = 0.419), but DR-FS of category D was better (p < 0.001) than those of B and C, and that of category A tended to be worse (p = 0.087) compared with those of B and C. Patients in category A, categories B and C, and category D could thus be classified as high-risk, intermediate-risk, and low-risk for distant recurrence, respectively. Conclusions: This study demonstrates the prognostic value of postoperative uTg and Tg-DR in Tg-Ab-negative patients with PTC under TSH suppression after total thyroidectomy. Prospective studies are needed to confirm these findings.