(I) To determine clinicopathological determinants of metachronous Upper Tract Urothelial Carcinoma (UTUC) requiring Radical Nephroureterectomy (RNU) after Radical Cystectomy (RC). (II) To evaluate long-term survival of patients who underwent RC + RNU compared with matched RC only controls.
Patients undergoing RNU for metachronous UTUC were extracted from a multi-institutional RC database. A 1:2 Propensity Score Match (PSM) was performed based on age, gender, BMI, CCI, Smoking Status, and cT stage between RC only and RC + RNU patients. Simon-Makuch plots, landmark analyses and Multivariable Cox regressions were adopted to compare survival outcomes.
Of 1804 RC patients, 85 (4.7%) underwent subsequent RNU. At multivariate regression, younger age, smoking history, BCG exposure, NMIBC, CIS and positive ureteric margins were identified as positive predictors of upper tract recurrence. After PSM, 81 RC + RNU patients were matched to 157 RC only controls. Median time from RC to RNU was 29 (18-47) months, with the majority of UTUC diagnosed at a muscle-invasive stage (70.9%). Simon-Makuch curves demonstrated worse Cancer Specific Survival (CSS) of the RC + RNU cohort (HR: 6.41, 95% CI 3.16-13.04). At landmark analyses, RNU was consistently associated with an increased mortality risk from the 24th month onward. Multivariable Cox regression identified RNU and pN + as the only significant predictors of worse CSS (respectively, HR: 6.55, 95% CI 2.93-14.64 and HR: 8.45, 95% CI 3.24-21.99).
The worse survival outcomes and high rates of locally advanced disease found at RNU underscore the need for standardized, risk-stratified, long-term follow-up of the remnant urinary tract following RC.
World journal of urology. 2026 Jun 10*** epublish ***
Valerio Santarelli, Vincenzo Asero, Roberta Corvino, Ettore De Berardinis, Alessandro Sciarra, Giuseppe Basile, Yasmin Abu-Ghanem, Rajesh Nair, Muhamad Shamin Khan, Ramesh Thurairaja, Wojciech Krajewski, Jan Laszkiewicz, Simone Albisinni, Keiichiro Mori, Felix Guerrero-Ramos, David D'Andrea, Andrea Gallioli, Ekaterina Laukhtina, Elisabeth Grobet-Jeandin, Maxence Reynard, Andrea Mari, Laura S Mertens, Francesco Soria, Jeremy Teoh, Francesco Claps, Antonio Amodeo, Aleksander Ślusarczyk, Roberto Contieri, Sisto Perdonà, José Daniel Subiela, Karl H Tully, Renate Pichler, Alessandro Antonelli, Riccardo Bertolo, Francesco Ditonno, Rodolfo Hurle, Felice Crocetto, Roman Mayr, Angelo Porreca, Filippo Marino, Giuseppe Simone, Gabriele Tuderti, Bernardo Maria Cesare Rocco, Chiara Sighinolfi, Luigi Vittori, Marco Moschini, Paolo Zaurito, Mario De Angelis, Pietro Scillipoti, Luca Afferi, Ruben De Groote, Geert De Naeyer, Alexandre Mottrie, Nicola Pavan, Benjamin I Chung, Gautier Marcq, Benjamin Pradere, Francesco Del Giudice, European Association of Urology -Young Academic Urologists (EAU -YAU), Urothelial Carcinoma Working Group
Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, Rome, Italy. ., Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, Rome, Italy., Department of Urology, Royal Free London Foundation Trust, London, UK., Guy's and St. Thomas' NHS Foundation Trust, Guys and St. Thomas' Hospital, London, UK., Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland., Unit of Urology, Department of Surgical Sciences, Tor Vergata University, Rome, Italy., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, Fundació Puigvert, Barcelona, Spain., Division of Urology, Geneva University Hospitals, Geneva, Switzerland., Unit of Oncologic Minimally-Invasive Urology and Andrology, Department of Clinical and Experimental Medicine, Careggi Hospital, University of Florence, Florence, Italy., Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Surgical Sciences, University of Turin and Città della Salute e della Scienza, Turin, Italy., Department of Surgery, S.H. Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong., Veneto Institute of Oncology IOV - IRCCS, Padua, Italy., Department of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland., Department of Urology, National Cancer Institute, IRCCS Fondazione G. Pascale, Naples, Italy., Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Universidad de Alcala, Madrid, Spain., Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany., Department of Urology, Comprehensive Cancer Centre Innsbruck, Medical University of Innsbruck, Innsbruck, Austria., Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Department of Urology, Humanitas Clinical and Research Hospital, IRCCS, Milano, Italy., Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy., Department of Urology, University Hospital Augsburg, Augsburg, Germany., Department of Urology, Humanitas Gavazzeni, 24125, Bergamo, Italy., Department of Urology, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Department of Urology, 'A. Gemelli' Hospital Foundation, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy., Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Department of Urology, IRCCS San Raffaele Hospital, Milan, Italy., Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland., Orsi Academy, Melle, Belgium., Department Me.Pre.Cc, Precision Medicine in Medical, Surgical, and Critical Areas, Section of Urology, University of Palermo, Palermo, Italy., Department of Urology, Stanford University School of Medicine, Stanford, USA., Department of Urology, Claude Huriez Hospital, CHU Lille, Lille, France., Department of Urology, St. Josef Medical Center, University of Regensburg, Regensburg, Germany.