Background: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.
Keywords: extrathyroidal extension; lymph nodes metastases; papillary thyroid carcinoma; recurrence; response to therapy.