About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care.
This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy.
The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.
Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively).
Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.
Targeted oncology. 2024 May 05 [Epub ahead of print]
Ondřej Fiala, Sebastiano Buti, Aristotelis Bamias, Francesco Massari, Renate Pichler, Marco Maruzzo, Enrique Grande, Ugo De Giorgi, Javier Molina-Cerrillo, Emmanuel Seront, Fabio Calabrò, Zin W Myint, Gaetano Facchini, Ray Manneh Kopp, Rossana Berardi, Jakub Kucharz, Maria Giuseppa Vitale, Alvaro Pinto, Luigi Formisano, Thomas Büttner, Carlo Messina, Fernando Sabino M Monteiro, Nicola Battelli, Ravindran Kanesvaran, Tomáš Büchler, Jindřich Kopecký, Daniele Santini, Giulia Claire Giudice, Camillo Porta, Matteo Santoni
Department of Oncology and Radiotherapeutics, Faculty of Medicine, University Hospital in Pilsen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic. ., Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126, Parma, Italy., Second Propaedeutic Department of Internal Medicine, School of Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria., Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy., Department of Medical Oncology, MD Anderson Cancer Center Madrid, Universidad Francisco de Vitoria, Madrid, Spain., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain., Medical Oncology, Cliniques universitaires Saint-Luc, Centre Hospitalier de Jolimont Institut Roi Albert II, Haine Saint Paul, Brussels, Belgium., Medical Oncology 1-IRCCS Regina Elena National Cancer Institute, Rome, Italy., Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA., Oncology Operative Unit, Santa Maria delle Grazie" Hospital, ASL NA2 NORD, Pozzuoli, Naples, 80078, Italy., Clinical Oncology, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Department of Medical Oncology, Università Politecnica delle Marche, AOU delle Marche, Ancona, Italy., Department of Uro-oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41124, Modena, Italy., Medical Oncology Department, La Paz University Hospital, Madrid, Spain., Department of Medicine and Surgery, Federico II University, Naples, Italy., Department of Urology, University Hospital Bonn (UKB), 53127, Bonn, Germany., Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy., Latin American Cooperative Oncology Group, LACOG and Oncology and Hematology Department, Hospital Sirio-Libanês, SGAS 613 Lote 94, Brasília, DF, Brazil., Oncology Unit, Macerata Hospital, Macerata, Italy., National Cancer Centre, Singapore, Singapore., Department of Oncology, Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic., Department of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic., Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Policlinico Umberto1, Rome, Italy., Interdisciplinary Department of Medicina, Division of Medical Oncology, University of Bari "Aldo Moro", A.O.U. Consorziale Policlinico di Bari, Bari, Italy.