Kinetic Analysis of Growth Activity in Enlarging Papillary Thyroid Microcarcinomas

Background: Although papillary thyroid microcarcinoma (PMC) is generally stable on active surveillance, conversion surgery is recommended for enlarging tumors. However, it remains unclear which enlargement threshold should be considered sufficient to trigger surgery. This study analyzed changes in the growth activity of PMC, before and after enlargement. Methods: We enrolled 824 patients with PMC, in whom active surveillance was initiated between 2005 and 2011 (median duration of follow-up: 6.04 years). Changes in the maximal tumor size and tumor volume were evaluated. Point of enlargement (PE) was defined as the time at which maximal tumor size or tumor volume had increased by ≥3 mm (PE-M) or by ≥50% (PE-V), respectively. In patients with PMC who underwent at least three ultrasound examinations during the study period, we compared the tumor doubling rates (TDRs, designated as the inverse of doubling time) between pre- and post-PEs. Results: Ten-year enlargement-free survival rates based on maximal tumor size and tumor volume were 86.9% and 54.9%, respectively. The median post-PE TDRs was significantly lower than that of pre-PEs (-0.091/year vs. 0.509/year [ p  < 0.001] for PE-M, and -0.058/year vs. 0.370/year [ p  < 0.001] for PE-V), indicating decreased tumor growth after PEs. After PE-M and PE-V, the PMCs continued to rapidly enlarge (TDR >0.5/year) in only 6 (7.7%) and 11 (3.8%) patients and moderately enlarge (TDR 0.1-0.5/year) in 10 (12.8%) and 35 (12.1%) patients, respectively. Conversely, tumors shrank (TDR < -0.1/year) in 37 (47.4%) and 105 (36.1%) patients, respectively, and remained stable (TDR ranged between 0.1/year and -0.1/year) in 25 (32.1%) and 140 (48.1%) patients, respectively. Conclusion: Since most PMCs demonstrate a significant decrease in growth activity after enlargement, performing surgery immediately after the PE may be premature.