Association of Extrarenal Invasion Patterns and Tumor Size with the Differences in Survival Outcomes of T3a Renal Cell Carcinoma: A Proposal Modified T3a Stage System is Needed

Objective: T3a renal cell carcinoma (RCC) did not consider tumor size and different extrarenal invasion patterns in the current TNM staging system. Here, we want to investigate the association of survival outcomes with different extrarenal invasion patterns and tumor size of T3a RCC. Methods: We identified T3a RCC patients from the Surveillance, Epidemiology, and End Results database in 2004-2015. The extrarenal invasion patterns included renal vein invasion, renal sinus/peri-sinus fat invasion, or perinephric fat invasion. Cox proportional hazards models and Fine and Gray models were used to estimate overall survival (OS) and cancer-specific survival (CSS), and the hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. C-index is used to evaluate the predictive ability of the model. Restricted cubic splines were used to estimate the HRs of tumor size on the risk of OS and CSS. Results: In total, 4834 T3a RCC patients were included in the analysis. Of them, 1403 (29%) present isolated extrarenal invasion pattern, while 1403 (71%) were any combined invasion pattern, which was associated with a higher risk of lymph-node/distant metastasis and a worse OS and CSS compared with isolated extrarenal invasion pattern, but a comparable CSS and OS were observed between each isolated invasion pattern. In restricted cubic splines, a non-linear shape was observed for the association between the tumor size and OS and CSS, compared with the smallest tumor size group (<= 4cm), the adjusted HR of the largest tumor size group (>= 10cm) was 1.59 for all-cause mortality, and 2.27 for tumor-specific mortality, respectively. However, in a cohort of T3a RCC with a combined invasion pattern, tumor size is not an independent risk factor for prognosis. Finally, the model added two covariates of tumor size and invasion patterns that could improve the predictive ability of OS and CSS for T3a patients (c-index: +1.2%, +1.3%, respectively). Conclusion: Tumor size and extrarenal invasion type are valid parameters of the OS and CSS for T3a RCC patients and need to be considered for the next generation of the T-stage system.