Nephroureterectomy for upper tract urothelial carcinoma recurrence in bladder cancer patients treated with radical cystectomy: a multicentric propensity score matched analysis on predictors, practice patterns and survival outcomes

World Journal of Urology (2026) 44:419 https://doi.org/10.1007/s00345-026-06520-z RESEARCH Nephroureterectomy for upper tract urothelial carcinoma recurrence in bladder cancer patients treated with radical cystectomy: a multicentric propensity score matched analysis on predictors, practice patterns and survival outcomes Valerio Santarelli1,2,3 · Vincenzo Asero1 · Roberta Corvino1 · Ettore De Berardinis1 · Alessandro Sciarra1 · Giuseppe Basile4 · Yasmin Abu-Ghanem5 · Rajesh Nair5 · Muhamad Shamin Khan5 · Ramesh Thurairaja5 · Wojciech Krajewski6 · Jan Laszkiewicz6 · Simone Albisinni7 · Keiichiro Mori8 · Felix Guerrero-Ramos9 · David D’Andrea10 · Andrea Gallioli11,12 · Ekaterina Laukhtina10 · Elisabeth Grobet-jeandin13 · Maxence Reynard13 · Andrea Mari14 · Laura S. Mertens15 · Francesco Soria16 · Jeremy Teoh17 · Francesco Claps18 · Antonio Amodeo18 · Aleksander Ślusarczyk19 · Roberto Contieri20 · Sisto Perdonà20 · José Daniel Subiela21 · Karl H. Tully22 · Renate Pichler23 · Alessandro Antonelli24 · Riccardo Bertolo24 · Francesco Ditonno24 · Rodolfo Hurle25 · Felice Crocetto26 · Roman Mayr27 · Angelo Porreca28 · Filippo Marino28 · Giuseppe Simone29 · Gabriele Tuderti29 · Bernardo Maria Cesare Rocco30 · Chiara Sighinolfi30 · Luigi Vittori31 · Marco Moschini32 · Paolo Zaurito32 · Mario De Angelis32 · Pietro Scillipoti32 · Luca Afferi33 · Ruben De Groote2,34 · Geert De Naeyer2,34 · Alexandre Mottrie2,34 · Nicola Pavan35 · Benjamin I. Chung3 · Gautier Marcq36 · Benjamin Pradere37 · Francesco Del Giudice1,3 · On behalf of the European Association of Urology -Young Academic Urologists (EAU -YAU), Urothelial Carcinoma Working Group Received: 12 April 2026 / Accepted: 30 May 2026 © The Author(s) 2026 Abstract Aim (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. Methods 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. Results 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). Conclusions 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. Keywords Radical cystectomy · Radical Nephroureterectomy · Upper tract urothelial carcinoma · Urothelial recurrence · Bladder cancer Extended author information available on the last page of the article 419 Page 2 of 12 Introduction Upper Urinary Tract (UUT) recurrence in the remnant urothelium represents a persistent, life-long risk following Radical Cystectomy (RC) [1]. Accordingly, latest European Association of Urology (EAU) guidelines suggest stringent UUT follow-up schedules for BC patients, with 4–10% of RC patients developing an Upper Urinary Tract Urothelial Carcinoma (UTUC). Radical nephroureterectomy (RNU) is the standard of care for high-risk UTUC [2, 3]. However, RNU following RC represents an additional burden in the already demanding treatment pathway for urothelial disease. Notably, only few risk factors for UUT recurrence have been previously identified [1, 4]. Among these, bladder carcinoma in situ (CIS), multifocal disease, non-muscle invasive bladder cancer (NMIBC), and involvement of the distal ureter or prostatic urethra are recognized as the most prominent predictors for secondary UTUC [4]. Beyond these pathology-based features, limited evidence exists regarding the influence of surgical approach during RC, type of urinary diversion, and patient-related risk factors. Despite the well-accepted recurrence risk, an effective standardized and risk-stratified follow-up regimen after RC for BC is still lacking [5]. Particularly, no consensus was reached regarding the timing of urinary cytology or the role of cross-sectional imaging in detecting late recurrences (i.e., beyond 5 years), which frequently involve the UUT [6, 7]. Besides its direct impact on cancer-specific survival outcomes, UTUC recurrence and its subsequent treatment further compromise overall health status primarily by worsening renal function and ultimately increasing cardiovascular events and all-cause deaths [2, 5, 6]. To date, real-world evidence on non-pathological determinants of UTUC recurrence after RC remains scarce. Moreover, limited data are available regarding the impact of RNU on survival outcomes of RC patients. To address this gap, we specifically selected patients who underwent RC for BC and subsequently RNU for an UUT recurrence to evaluate clinical and pathological determinants of UUT recurrence. After Propensity Score Matching on selected preoperative clinical characteristics, long-term survival outcomes were finally evaluated. Materials and methods Study population Data from 23 tertiary referral centers in Europe, North America and Asia on patients who underwent RC with curative intent from 2005 to 2024 was collected from a multi-institutional, prospectively maintained database of 13 World Journal of Urology (2026) 44:419 the Young Academic Urologists (YAU)—Urothelial Carcinoma Working Group. Subsequently, the same dataset was retrospectively reviewed to extract patients who developed a UUT recurrence requiring RNU. Before study initiation, data-transfer agreement and Institutional Review Boards (IRB) approval from each of the included centers were obtained. All patient-related information was anonymized prior to data sharing. Exclusion criteria were previous Radiation Therapy or Chemotherapy performed for other purposes other than a Neoadjuvant/Adjuvant setting, RC performed for other indications rather than curative intent for a cN0M0 BC, estimated life expectancy < 5 years and concomitant or previous RNU. Statistical analysis Statistical analyses were cond (...truncated)