BACKGROUND: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN). OBJECTIVE: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting. METHODS: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis. CONCLUSION: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology Medical University of Vienna Vienna Austria; Department of Special Surgery Jordan University hospital The University of Jordan Amman Jordan

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology Jikei University School of Medicine Tokyo Japan

Department of Urology Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia; Department of Urology Weill Cornell Medical School New York NY; Department of Urology University of Texas Southwestern Medical Center Dallas TX; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany; Department of Urology Medical University of Vienna Vienna Austria

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