Introduction: Sarcomatoid dedifferentiation may be identified in both clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC). Within the SEER database (2010-2021), we tested the effect of sarcomatoid dedifferentiation in first ccRCC and subsequently in nccRCC on cancer-specific mortality (CSM). Methods: Separate propensity score matching (PSM) and multivariable competing risks regression (CRR) analyses were first applied to ccRCC with vs. without sarcomatoid dedifferentiation and subsequently to nccRCC with vs. without sarcomatoid dedifferentiation. Results: Sarcomatoid dedifferentiation was present in 2496 (3.0%) of 82,146 ccRCC patients and in 501 (1.9%) of 26,584 nccRCC. In ccRCC, after 1:2 PSM, 2496 (100%) patients with sarcomatoid dedifferentiation vs. 4992 (6.2%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 45.7% vs. 33.6% in ccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 1.6-fold higher CSM (HR 1.6, p < 0.001). In nccRCC, after 1:2 PSM 501 (100%) patients with sarcomatoid dedifferentiation vs. 1002 (3.8%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 41.7% vs. 28.1% in nccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 2.0-fold higher CSM (HR 2.0, p < 0.001). Conclusion: Sarcomatoid dedifferentiation is invariably associated with higher CSM in both ccRCC and nccRCC. However, the detrimental effect of sarcomatoid dedifferentiation in CSM is more pronounced in nccRCC than in ccRCC.
Journal of clinical medicine. 2026 Mar 11*** epublish ***
Michele Nicolazzini, Calogero Catanzaro, Federico Polverino, Michele Petix, Maximilian Filzmayer, Leonardo Quarta, Jordan A Goyal, Riccardo Schiavina, Nicola Longo, Gennaro Musi, Felix K H Chun, Alberto Briganti, Shahrokh F Shariat, Carlotta Palumbo, Fred Saad, Alessandro Volpe, Pierre I Karakiewicz
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC H2X 0A9, Canada., Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy., Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy., Università degli Studi di Milano, 20122 Milan, Italy., Department of Urology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany., Division of Experimental Oncology, Unit of Urology, URI-Urological Research Institute, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria., Division of Urology, Department of Translational Medicine, Maggiore della Carità Hospital, University of Eastern Piedmont, 28100 Novara, Italy.