In metastatic clear-cell renal cell carcinoma (ccmRCC), sarcomatoid dedifferentiation is routinely reported in G4 patients, but routine reporting is not recommended in G3 patients. We tested independent predictor status of sarcomatoid dedifferentiation in G4 ccmRCC. Additionally, we explored whether sarcomatoid dedifferentiation may have a role in overall mortality (OM) prediction in G3 ccmRCC.
Within the Surveillance, Epidemiology, and End Results database, univariable and multivariable Cox-regression models assessed cytoreductive nephrectomy (CN)-treated ccmRCC patients (2010-2020).
Of 2644 CN-treated ccmRCC patients, 1336 (51 %) harbored G4, of whom 528 (40 %) harbored sarcomatoid dedifferentiation. In G4, median overall survival (OS) according to presence vs. absence of sarcomatoid dedifferentiation was 20 vs. 21 months (p = 0.6) and sarcomatoid dedifferentiation was not independent predictor in multivariable analyses. Of all, 1308 (49 %) harbored G3, of whom 79 (6 %) harbored sarcomatoid dedifferentiation. In G3, median OS according to presence vs. absence of sarcomatoid dedifferentiation was 22 vs. 38 months (p < 0.001) and sarcomatoid dedifferentiation independently predicted higher OM in multivariable analyses (hazard ratio 1.7, p < 0.001).
Reporting of sarcomatoid dedifferentiation in G4 RCC is routinely recommended. However, in G4 ccmRCC, presence of sarcomatoid dedifferentiation does not independently predict higher OM and its inclusion is not essential in multivariable considerations in G4 patients. Conversely, despite absence of standard reporting recommendation for sarcomatoid dedifferentiation in G3, presence of sarcomatoid dedifferentiation is associated with significantly higher mortality and achieved independent predictor status. Therefore, it possibly should be routinely reported and routinely included in multivariable analyses addressing G3 ccmRCC patients.
Surgical oncology. 2025 Oct 24 [Epub ahead of print]
Reha-Baris Incesu, Lukas Scheipner, Simone Morra, Andrea Baudo, Carolin Siech, Letizia Maria Ippolita Jannello, Mario de Angelis, Anis Assad, Zhe Tian, Fred Saad, Shahrokh F Shariat, Alberto Briganti, Ottavio de Cobelli, Felix K H Chun, Luca Carmignani, Nicola Longo, Sascha Ahyai, Derya Tilki, Markus Graefen, Pierre I Karakiewicz
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, Medical University of Graz, Graz, Austria., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milan, Italy; Department of Urology, IRCCS Policlinico San Donato, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, 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 Medical Center, Dallas, TX, USA; Hourani Center of Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan., Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy., Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany., Department of Urology, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milan, Italy; Department of Urology, IRCCS Policlinico San Donato, Milan, Italy., Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy., Department of Urology, Medical University of Graz, Graz, Austria., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.