Proposal for reclassification of upstaged T1 and T2 and pathological T3 RCC based on improved alignment of survival analyses.

732 Background: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. However, we do know that original clinical tumor staging does still predict outcomes. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Patients were analyzed for demographics, clinical parameters, and post-surgical outcomes. Primary outcome was cancer specific mortality (CSM). Secondary outcomes were all cause mortality and recurrence free survival. Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year cancer specific survival. ROC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. Results: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p<0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p<0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened cancer specific mortality, while cT1/pT3 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) were associated with improved cancer specific mortality. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year cancer specific survival (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p<0.001). There were significant differences in 5-year overall survival (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p<0.001), and 5-year recurrence free survival (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p<0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. Conclusions: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making.