Association Between Systemic Therapy and/or Cytoreductive Nephrectomy and Survival in Contemporary Metastatic Non-clear Cell Renal Cell Carcinoma Patients.

Optimal management of metastatic non-clear cell renal cell carcinoma (non-ccmRCC) remains largely unknown.

To test the effect of systemic therapy (ST) and/or cytoreductive nephrectomy (CNT) on overall mortality (OM) in patients with non-ccmRCC.

Within the Surveillance, Epidemiology and End Results (SEER) registry (2006-2015), we identified patients with papillary, chromophobe, sarcomatoid, and collecting duct metastatic renal cell carcinoma (mRCC).

Temporal trends (estimated annual percentage change [EAPC]), Kaplan-Meier plots, and multivariable Cox regression models were used.

Of 1573 patients with non-ccmRCC, 22%, 25%, 25%, and 28% underwent no treatment, ST, CNT, and CNT with ST, respectively. Between 2006 and 2015, rates of CNT and the combination of CNT and ST decreased (EAPC: -6.3% and -3.2%, respectively). Conversely, rates of no treatment and ST increased over time (EAPC: 4.6% and 7.5%, respectively). In multivariable Cox regression models, relative to no treatment, ST (hazard ratio [HR]: 0.5; p < 0.001), CNT (HR: 0.4; p < 0.001), and CNT with ST (HR: 0.3; p < 0.001) were associated with lower OM. Histological subtypes were associated with OM, relative to papillary renal cell carcinoma (RCC): chromophobe (HR: 0.7; p < 0.01), sarcomatoid (HR: 2.1; p < 0.001), and collecting duct RCC (HR: 1.9; p < 0.001). Limitations include the impossibility to stratify patients according to mRCC risk groups.

Most non-ccmRCC patients are treated with a combination of CNT and ST or CNT alone or ST alone. The rates of ST alone are increasing. Conversely, the rates of combined CNT and ST and CNT alone are decreasing. These observed temporal patterns of treatment rates are counterintuitive with respect to associated OM benefits, where combination of CNT and ST, as well as CNT alone, resulted in the lowest absolute OM, relative to ST alone, or, even worse, no treatment.

We investigated the effect of treatment modalities on survival of patients with metastatic non-clear cell renal cell carcinoma. The combination of cytoreductive nephrectomy and systemic therapy confers greater benefit with respect to single treatments alone.

European urology focus. 2020 May 19 [Epub ahead of print]

Stefano Luzzago, Carlotta Palumbo, Giuseppe Rosiello, Sophie Knipper, Angela Pecoraro, Francesco Alessandro Mistretta, Zhe Tian, Gennaro Musi, Emanuele Montanari, Denis Soulières, Shahrokh F Shariat, Fred Saad, Alberto Briganti, Ottavio de Cobelli, Pierre I Karakiewicz

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy. Electronic address: ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Urology Unit, ASST Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Turin, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada., Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy., Department of Urology, IRCCS Fondazione Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy., Department of Hematology-Oncology, University of Montreal Hospital Centre (CHUM), Montreal, Quebec, Canada., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.