Does timing of cytoreductive nephrectomy impact patient survival with metastatic renal cell carcinoma in the tyrosine kinase inhibitor era? A multi-institutional study

Objective: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients who underwent primary cytoreductive nephrectomy (CRN), followed by adjuvant sunitinib therapy, vs those who underwent primary sunitinib therapy before planned CRN. Methods: This was a multi-institutional retrospective analysis of 35 mRCC patients from June 2005 to August 2009 (median follow-up, 28.5 months): 17 underwent primary CRN, followed by adjuvant sunitinib (group 1); 18 underwent primary sunitinib therapy, followed by planned CRN (group 2). Response to therapy was determined using Response Evaluation Criteria in Solid Tumors. Group 2 patients who had partial response (PR)/stable disease (SD) proceeded to CRN (group 2 +CRN). Group 2 patients who progressed were treated with salvage systemic therapy (group 2 no-CRN). Primary and secondary outcomes were disease-specific survival (DSS) and overall survival (OS). Results: Patient demographic and tumor characteristics were similar. The groups had similar rates of DSS and OS on univariate analysis (P =.318 and P =.181). In group 2, 11 (61%) had PR/DS; 7 (39%) progressed. Mean times to disease-specific death in group 1, group 2 (+CRN), and group 2 (no-CRN) were 29.2, 4.6, and 28.7 months, respectively (P =.025). Kaplan-Meier analysis of DSS and OS demonstrated significant improvement in group 2 (+CRN) vs group 1 vs group 2 (no-CRN; P <.001), which remained significant on multivariate regression. Conclusion: Nonresponders to primary sunitinib therapy had a poor prognosis. Offering CRN, if safely feasible, combined with sunitinib, was associated with improved disease-specific outcome in mRCC. Responders to primary sunitinib who underwent CRN had better DSS and OS than patients who underwent primary CRN, followed by sunitinib. Further investigation is required to assess the role, timing, and sequencing of targeted therapy and CRN in treatment of mRCC.