Reclassification of pathologically upstaged T3a Renal Cell Carcinoma is associated with enhanced alignment of outcomes: Analysis of the National Cancer Database.

Abstract

Purpose: To compare outcomes of pathological T3a renal cell carcinoma (RCC) based on clinical stage at presentation, and to propose reclassification of T3a RCC based on survival outcomes, as outcomes of current T3a RCC may vary based on initial clinical presentation.

Methods: Using the National Cancer Database, patients with pT2 and pT3aN0M0 RCC were categorized by AJCC clinical T stage. Primary outcome was overall survival (OS). Multivariable analysis (MVA) assessed predictors for all-cause mortality (ACM), controlling for presenting clinical T stage. Kaplan-Meier Analysis (KMA) assessed differences between cT1-upstaged pT3a (cT1→pT3a), cT2-upstaged pT3a (cT2→pT3a), clinical/pathological T2 (cT2→pT2), and clinical/pathological T3a (cT3a→pT3a) RCC, and a modified T3a RCC was created based on clustering of survival outcomes between clinical staging groups. ROC/AUC analysis was utilized to compare predictive value of AJCC 8^th edition staging vs. proposed staging.

Results: 45,097 patients with pT3a disease were analyzed (9,730 cT1→pT3a; 7,209 cT2→pT3a, 19,857 cT2→pT2; and 8,301 cT3a→pT3a). MVA for OS [cT1→pT3a (referent)] demonstrated cT2→pT3a (HR=1.27, p<0.001) and cT3a→pT3a (HR=1.20, p<0.001) were associated with worsened ACM, while cT2→pT2 (HR=0.95, p=0.052) was not significantly different. KMA for 5-year OS using current AJCC demonstrated: cT1→pT3a 73.1%, cT2→pT2 78.0%, cT2→pT3a 60.8%, cT3a→pT3a 59.9% (p<0.001). KMA for 5-year OS of a new pT2 group, comprised of cT1→pT3a and cT2→pT2, while maintaining cT2→pT3a and cT3a→pT3a as T3a was 78.0% vs. 60.3% (p=0.003). ROC analysis for OS revealed AUC of 0.532 (95% CI: 0.530-0.535) for T3 using current AJCC 8^th edition TNM staging and AUC of 0.573 (95% CI: 0.569-0.577) for proposed T3a reclassification (p<0.001).

Conclusion: Reclassification of cT1→pT3a and cT2→ pT2 into a new T2 RCC while maintaining cT2→pT3a and cT3a→pT3a RCC in T3a RCC resulted in improved performance of the realigned model for OS. Revised TNM criteria for pT2 and T3a RCC should be considered.