We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).
Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging.
429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500).
Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging.
Frontiers in oncology. 2023 Mar 29*** epublish ***
Margaret F Meagher, Maria C Mir, Andrea Minervini, Maximilian Kriegmair, Matthias Heck, Francesco Porpiglia, Siska Van Bruwaene, Estefania Linares, Vital Hevia, Maurizio D'Anna, Alessandro Veccia, Eduard Roussel, Francesco Claps, Carlotta Palumbo, Michele Marchioni, Jonathan Afari, Cesare Saitta, Franklin Liu, Jose Rubio, Riccardo Campi, Andrea Mari, Thomas Amiel, Enrico Checcucci, Mireia Musquera, Georgi Guruli, Nicola Pavan, Maarten Albersen, Alessandro Antonelli, Tobias Klatte, Riccardo Autorino, Rana R McKay, Ithaar H Derweesh
Department of Urology, University of California (UC) San Diego School of Medicine, La Jolla, CA, United States., Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain., Department of Urology, University of Florence, Careggi Hospital, Florence, Italy., Department of Urology, University Medical Centre Mannheim, Mannheim, Germany., Department of Urology, Technical University of Munich, Munich, Germany., Department of Urology, University of Turin-San Luigi Gonzaga Hospital, Orbassano, Italy., Department of Urology, AZ Groeninge, Kortrijk, Belgium., Department of Urology, Hospital 12 de Octubre, Madrid, Spain., Department of Urology, Hospital Ramon y Cajal, Madrid, Spain., Department of Urology, Hospital Clinic, Carrer de Villarroel, Barcelona, Spain., Department of Urology, Virginia Commonwealth University (VCU) Medical Center, Richmond, VA, United States., Department of Urology, UK Leuven, Leuven, Belgium., Department of Urology, University of Trieste, Trieste, Italy., Department of Urology, Spedali Civili Hospital, University of Brescia, Brescia, Italy., Department of Urology, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy., Department of Urology, Royal Bournemouth Hospital, Bournemouth, United Kingdom.