Deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma: A systematic review and patient-level meta-analysis

There has been much controversy regarding the order in which cytoreductive nephrectomy (CN) and systemic therapy (ST) are applied for patients with metastatic renal cell carcinoma (mRCC). We aimed to investigate the role of deferred CN (dCN) in mRCC, particularly in the current era of immunotherapy. A systematic literature search was conducted on PubMed, Embase, and Scopus for studies comparing dCN versus any non-dCN strategy, in any temporal sequence, with the provision of Kaplan-Meier curves for overall survival (OS). A graphical reconstructive algorithm was used to obtain OS of individual patients, which was then pooled under random-effects individual patient data (IPD) meta-analysis using Cox-models to determine hazard ratios (HRs) and 95% CI. Altogether, 12 studies (5,350 patients) were analyzed. dCN (ST followed by CN) was associated with significantly improved OS over nondeferred CN (CN followed by ST, ST alone, or CN alone) (HR = 0.60, 95% CI, 0.53-0.67, P < 0.001). Subgroup comparisons restricted to studies comparing dCN versus upfront CN (uCN, CN then ST) were also in favor of dCN (HR = 0.69, 95% CI, 0.61-0.78, P < 0.001), even among those in which immunotherapy as ST was used in all patients (HR = 0.57, 95% CI, 0.39-0.84, P = 0.005). In mRCC patients suitable for CN, dCN is associated with significantly improved OS over nondeferred CN strategies, including uCN. Although limited by inclusion of nonrandomized studies and immortal time bias, this meta-analysis strengthens existing guidelines to offer dCN to surgically fit patients who do not progress on ST in the current age of immunotherapy.