Intermediate-Risk Papillary Thyroid Cancer: Risk Factors for Early Recurrence in Patients with Excellent Response to Initial Therapy

Background: Patients with excellent response to initial therapy have a low rate of tumor recurrence. The objectives of this study were to evaluate the rate of early tumor recurrence in patients with intermediate-risk papillary thyroid cancer who had an excellent response to initial treatment and to identify risk factors. Methods: This retrospective cohort study included 217 patients with American Thyroid Association intermediate-risk papillary thyroid cancer who had a documented excellent response to initial treatment (total thyroidectomy and adjuvant therapy with 100-150 mCi [3.7-5.5 GBq] of radioactive iodine [RAI]). The assessed outcome was recurrence, defined as new evidence of disease after any disease-free period. Multivariate logistic regression and Cox regression models were used to determine the factors associated with recurrence upon recording clinical, surgical, and pathology variables. Results: Sixteen (7.4%) cases of recurrent disease were documented after a median follow-up period of 42 months (range 17-88 months). Structural recurrence was documented in 10 (62.5%) patients, and biochemical recurrence was documented in the remaining six patients. The logistic regression model identified a significant association between early recurrence and pN1b involvement (odds ratio [OR] = 10.81 [confidence interval (CI) 1.87-62.59]), lateral neck RAI uptake (OR= 6.06 [CI 1.67-22]), and pre-ablation thyroglobulin >10 ng/mL (OR= 4.01 [CI 1.16-13.85]). Variables that proved significant in the Cox regression model were: pN1b involvement (hazard ratio = 9.6 [CI 1.91-48.52]) and lateral neck RAI uptake (hazard ratio = 5.95 [CI 1.86-18.97]). Conclusion: The observed early recurrence rate of 7.4% is uncharacteristically high for a population of patients who had an excellent response to initial treatment. The significant association that was found between recurrent disease and lateral neck lymph node metastasis, lateral neck I 131 uptake in post-therapy whole-body scan, and preablation thyroglobulin levels > 10 ng/mL indicates that early recurrence (<5 years) most likely indicates progression of micrometastatic disease already present at diagnosis and unsuccessfully eradicated with initial therapy.