Total thyroidectomy (TT) is recommended for papillary thyroid cancer (PTC) over 4 ​cm, but its universal benefit is uncertain. This study evaluates whether TT offers a significant advantage over lobectomy (LT) in improving overall survival (OS) and cancer-specific survival (CSS) for patients with unilateral PTC exceeding 4 ​cm.

The study included 8862 patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2021) with unilateral PTC larger than 4 ​cm. The relationship between age and survival was assessed using the restricted cubic splines (RCS) model. The effects of LT and TT on OS and CSS across age groups were analyzed using Cox regression and Kaplan-Meier (KM) methods, with and without age stratification. Propensity score matching (PSM) and sensitivity analyses were conducted to assess the robustness of the results.

TT did not improve OS (P ​= ​0.888) or CSS (P ​= ​0.907) compared to LT in the overall cohort. However, TT significantly improved OS (HR ​= ​0.54, P ​= ​0.004) and CSS (HR ​= ​0.55, P ​= ​0.018) in high-risk patients (T4, N1, or M1 stage), but not in low-risk patients. Age-stratified analysis showed TT benefited only young (18–55 years) high-risk patients, enhancing OS (HR ​= ​0.29, P ​= ​0.001) and CSS (HR ​= ​0.35, P ​= ​0.035). Older patients did not gain significant survival advantages from TT, regardless of risk status. These results were consistent in the PSM and sensitivity analyses.

TT may not be the best approach for all unilateral PTC patients over 4 ​cm in terms of OS and CSS. It improves survival outcomes in young patients with advanced TNM stages but does not confer a significant OS or CSS advantage over LT for older or low-risk patients.