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The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses. <b><i>Methods:</i></b> We studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29–48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management). <b><i>Results:</i></b> Of the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14–22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71–126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status. <b><i>Conclusions:</i></b> The response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.

Context Controversy surrounds the extent and intensity of the management of the American Thyroid Association (ATA) intermediate and low risk patients with differentiated thyroid cancer (DTC). Understanding the natural history and factors that predict outcome is important for properly tailoring the management of those patients. Objective To study the natural course and predictive factors of incomplete response to therapy in low and intermediate risk DTC. Patients and Methods We studied a cohort of 506 consecutive patients (418 females [(82.6%) and 88 males (17.4%)] with low and intermediate risk with a median age of 35 years (IQR 27-46). We analyzed the natural course and the predictive factors of biochemically or structurally incomplete response. Results Of 506 patients studied, 297 (58.7%) patients were in low and 209 (41.3%) in intermediate risk groups. Over a median follow up of 102 months (IQR 66-130), 458 (90.5%) patients achieved an excellent response, 17 (3.4%) were in biochemically incomplete and 31 (6.1%) in a structurally incomplete status. In univariate and multivariate analyses, age (≥ 33 years) (P &lt;0.0001, Odds ratio 1.06 (1.04-1.08) and lateral lymph node metastasis (LNM) (P &lt; 0.0001, Odds ratio 3.2 (1.7-5.9) were strong predictive factors for biochemically and structurally incomplete response to therapy. Sex, tumor size, multifocality, extrathyroidal extension and lymphovascular invasion did not predict incomplete response to therapy. Conclusions Patients with low and intermediate risk DTC have favorable outcome. Age and lateral LMN are strong predictors of an incomplete response to therapy. This suggests that older patients and those with LMN should be managed and followed up more proactively than younger patients and those without LMN.

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