Impact of timing of immunotherapy and cytoreductive nephrectomy on outcomes in metastatic renal cell carcinoma: Results from the CKCis database.

416 Background: Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC but its role and timing are not well-understood in the era of immunotherapy. The primary objective of this study is to assess patient outcomes in patients who received ST only, CN followed by ST (CN-ST) and ST followed by CN (ST-CN). Methods: The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST for mRCC between January 2014 to June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression free survival (PFS), after adjusting for IMDC risk group. Complications of ST and CN for these cohorts were collected. Results: A total of 588 patients were included in this study. 331 patients received ST only, 215 patients received CN-ST and 42 patients received at least one dose of ST prior to CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST and metastatic sites are reported and globally well-balanced. OS analysis favoured patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13-0.68) and CN-ST (HR 0.68, CI 0.47-0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26-0.77) and CN-ST (HR 0.9, CI 0.68-1.17). The most common cause of ST delay or cessation was treatment toxicity, followed by progression of disease. The most common perioperative complication was bleeding, followed by infection. Conclusions: This study examined baseline features and outcomes associated with the use and timing of CN and ST using real world data through the CKCis database. Patients selected to receive CN after ST seem to have improved outcomes. There were no appreciable differences in ST toxicity or perioperative complications across groups. Limitations include the small number of patients in the CN-ST group and residual confounding and selection bias that may influence the outcomes in patients undergoing CN.