The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC.
A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts.
In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.
Urologic oncology. 2024 Mar 04 [Epub ahead of print]
Selcuk Erdem, Riccardo Bertolo, Riccardo Campi, Umberto Capitanio, Daniele Amparore, Umberto Anceschi, Maria Carme Mir, Eduard Roussel, Nicola Pavan, Umberto Carbonara, Onder Kara, Tobias Klatte, Michele Marchioni, Angela Pecoraro, Stijn Muselaers, Laura Marandino, Pietro Diana, Leonardo Borregales, Carlotta Palumbo, Hannah Warren, Zhenjie Wu, Anna Calio, Chiara Ciccarese, Enes Degirmenci, Resat Aydin, Giacomo Rebez, Luigi Schips, Giuseppe Simone, Andrea Minervini, Sergio Serni, Faruk Ozcan
Division of Urologic Oncology, Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey; European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands. Electronic address: ., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, San Carlo Di Nancy Hospital, Rome, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Unit of Urological Robotic Surgery and Renal Transplantation, Department of Experimental and Clinical Medicine University of Florence, Florence, Italy., Department of Urology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; School of Medicine, Division of Urology, Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy., Department of Urology, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Department of Urology, IMED Hospital, Valencia, Spain., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, University Hospitals Leuven, Leuven, Belgium., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Unit of Andrology and Kidney Transplantation, Department of Emergency and Organ Transplantation-Urology, University of Bari, Bari, Italy., Department of Urology, Kocaeli University School of Medicine, Kocaeli, Turkey., Department of Urology, Helios Klinikum Bad Saarow, Bad Saarow, Germany., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, SS. Annunziata Hospital, G. D'Annunzio University, Chieti, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Division of Urology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, IRCCS Humanitas Clinic, Rozzano, Milan, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, Weill Cornell Medicine/New York-Presbyterian, New York, NY., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Division of Surgery and Interventional Science, University College London, London, UK., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Department of Diagnostic and Public Health, University of Verona, Verona, Italy., European Association of Urology (EAU), Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, Netherlands; Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey., Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy., Department of Urology, SS. Annunziata Hospital, G. D'Annunzio University, Chieti, Italy., School of Medicine, Division of Urology, Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy., Unit of Urological Oncologic Minimally-Invasive Robotic Surgery and Andrology, University of Florence, Florence, Italy., Unit of Urological Robotic Surgery and Renal Transplantation, Department of Experimental and Clinical Medicine University of Florence, Florence, Italy., Division of Urologic Oncology, Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.