Impact of upstaging from cT2a–b to pT3a on overall survival (OS) among patients with renal cell carcinoma.

601 Background: Identifying patients with renal cell carcinoma (RCC) who may benefit from adjuvant systemic therapy has proven difficult. Approximately 40% of patients with cT2a-b tumors will be upstaged to pT3a disease following surgery. These patients, given their large tumor size, may represent a higher risk cohort compared to patients with concordant T3a staging. We assessed OS among cT2a-b patients who were upstaged to pT3a compared to their cT3a counterparts with concordant pathologic staging. Methods: Using the National Cancer Database, we identified N0M0 adult patients with cT2a, cT2b, and cT3a RCC who underwent partial or radical nephrectomy and had pT3a disease on final pathology. We categorized patients into three groups: (1) cT2a to pT3a, (2) cT2b to pT3a, and (3) cT3a to pT3a. We compared OS between the groups using Kaplan Meier estimates and multivariable analysis using Cox proportional hazards models. Subgroup analysis of overall survival was performed for histology (clear cell vs non–clear cell). Results: 11,241 patients met inclusion criteria (3,067 cT2a, 1,893 cT2b, and 6,281 cT3a). Median pathological tumor size was 8.0, 11.2, and 7.5 cm for cT2a, cT2b and cT3a tumors, respectively. Mean 5-year OS was 37% for both cT2a and cT2b disease upstaged to pT3a and 48% for cT3a disease with concordant pathological staging (log rank p < 0.0001). This finding persisted on multivariable analysis (cT3a HR 0.81 [0.77–0.85], p < 0.001). Conclusions: Patients who were pathologically upstaged from cT2 to pT3a disease had worse OS compared to patients with concordant staging, a finding likely related to differences in median tumor size. Our findings imply that it is reasonable to include well-selected cT2 tumors in the next iteration of perioperative trials. However, those designing and conducting clinical trials must power their studies to adjust for heterogeneity in pathologic restaging.