Evaluation Of Disease-Free Survival As An Intermediate Metric For Overall Survival In Localized Renal Cell Carcinoma: A Trial-Level Meta-Analysis

4585 Background: Adjuvant trials aim to integrate systemic therapy earlier to increase cure rates over surgery alone. Overall survival (OS) is a critical endpoint for these studies but requires long durations to events and significant patient resources. We explored the potential use of disease-free survival (DFS) as an intermediate readout for OS in the adjuvant setting for localized renal cell carcinoma (RCC). Methods: We performed a systematic literature review following the PRISMA guidelines. Inclusion criteria required randomized controlled trials (RCT) for adjuvant systemic therapy in localized RCC, which reported on both DFS and OS. Data on hazard ratio (HR) and 5-year event-free rate from Kaplan-Meier estimates were extracted. We performed a trial level meta-analysis and correlated these estimates for OS and DFS, weighted by the number of DFS events. R-square > 0.7 would indicate a strong correlation and potential for surrogacy. Results: Thirteen RCTs encompassing 6,473 patients treated with various forms of systemic therapy were eligible for the analyses. Minimum follow-up was 40 months. There was a moderate correlation between 5-year DFS and 5-year OS rates (R-square = 0.49, 95% CI:0.15-0.68) and between treatment effects as measured by DFS and OS hazard ratios (R-square = 0.44, 95% CI:0.00-0.69). Conclusions: Across trials of adjuvant systemic therapy for localized RCC, we observed a moderate correlation between 5-year DFS and OS rates and between treatment effects (HRs) on these endpoints. Further granularity may be achieved using individual patient data to assess different and earlier time points for surrogacy than are commonly reported. [Table: see text]