Comparative Evaluation of TNM Staging Systems (eighth Vs. Ninth Edition) for the Non-surgical Treatment of Localized and Locally Advanced Anal Squamous Cell Carcinoma: Prognostic Significance of T Classification and Lymph Node Status

This study aims to compare the survival discrimination of the Tumor-Node-Metastasis (TNM) eighth and ninth editions for patients with localized and locally advanced (LLA) anal squamous cell carcinoma (ASCC) treated non-surgically and to evaluate the prognostic impact of T classification and lymph node (LN) status with data from the Surveillance, Epidemiology, and End Results database. We retrospectively included 6,876 patients in the comparison. We observed the inversion of survival outcomes for stages IIB and IIIA diseases in the TNM eighth edition [median overall survival (OS): 112 months for stage IIB vs. not reached for stage IIIA]. By contrast, it demonstrated improvement in the TNM ninth edition (median OS: not reached for IIB disease vs. 120 months for IIIA disease, P<0.001). In the correlation analysis, we observed an increased correlation between T classification and TNM staging systems (r value increased from 0.78 to 0.93) and a decreased correlation for the LN status (r value decreased from 0.83 to 0.59). For OS, variable importance analysis demonstrated more weight of importance for the T classification than the LN status (0.0871 vs. 0.0048). Additionally, decision curve analysis and time-dependent receiver operating characteristic analysis confirmed the prognostic accuracy of T classification rather than the LN status. In conclusion, TNM ninth edition is a better prognostic indicator than the eighth edition for patients with LLA ASCC treated non-surgically. T classification plays a more important prognostic role than the LN status and warrants further validation.