Radical cystectomy with pelvic lymph node dissection (PLND) remains the standard treatment for muscle-invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) improves survival, and recent immunochemotherapy trials have reported complete pathological responses in up to 60% of patients, increasing interest in bladder-sparing strategies. However, the ability to accurately identify patients without residual pelvic lymph node metastases after NAC remains limited.
To evaluate the association between pathological response in the bladder and pelvic lymph node status after NAC in patients with MIBC undergoing radical cystectomy (RC) and PLND.
This retrospective, multi-institutional cohort study included 751 patients with MIBC treated with NAC followed by RC and PLND between 2000 and 2021 across 26 institutions.
Neoadjuvant chemotherapy followed by RC and PLND.
The primary outcome was residual lymph node involvement (ypN+). Multivariable logistic regression was used to identify factors associated with ypN+.
Overall, 175 patients (23%) achieved a complete pathological response in the bladder (ypT0), 102 (14%) were downstaged to non-muscle-invasive disease (ypTa/ypTis/ypT1), and 185 (25%) had residual lymph node involvement. On multivariable analysis, cN+ disease before NAC was associated with higher odds of ypN+ (OR 1.97, 95% CI 1.32-2.94), whereas ypT0 (OR 0.11, 95% CI 0.05-0.21) and ypTa/ypTis/ypT1 (OR 0.24, 95% CI 0.12-0.47) were associated with lower odds of ypN+. Notably, 5% of ypT0 and 10% of downstaged patients harboured residual lymph node metastases. Limitations include potential selection bias and centre-level variability in surgical and pathological assessment, which may affect the generalizability of the findings.
Current clinical and radiological variables cannot reliably exclude residual pelvic lymph node disease, even in patients achieving ypT0-1. Novel imaging techniques and liquid biomarkers require validation before bladder-sparing approaches can be safely expanded.
European urology focus. 2026 Jul 28 [Epub ahead of print]
Luca Antonelli, Luca Afferi, Francesco Del Giudice, Eugenio Bologna, Francesco Esperto, Francesco Chierigo, Alessandro Antonelli, Karl Tully, Paolo Umari, Simone Albisinni, Andrea Mari, Renate Pichler, Francesco Claps, Jeremy Yuen-Chun Teoh, Mathieu Roumiguié, Gerald Bastian Schulz, Luca Orecchia, Francesco Soria, Morgan Roupret, Gautier Marcq, Cedric Poyet, Girish S Kulkarni, Michael Rink, Tobias Klatte, Riccardo Campi, Wojciech Krajewski, Laura Mertens, Meftun Culpan, Luke T Lavallée, Marco Moschini, Christian Daniel Fankhauser, 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 Urology, Luzerner Kantonsspital, University of Lucerne, Switzerland. Electronic address: ., Department of Urology, Kantonsspital Aarau, Aarau, Switzerland., Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy., Department of Urology, Campus Bio-Medico University, Rome, Italy., Department of Urology, Department of Health Science, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy., Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy., Department of Urology and Neurourology, Marien Hospital Herne, Ruhr University, Bochum, Germany., St. George's University Hospital, London, United Kingdom., Service d'Urologie, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium; Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, Rome, Italy., Unit of Oncologic Minimally-Invasive Urology and Andrology - Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Italy., Department of Urology, Medical University of Innsbruck, Innsbruck, Austria., Urological Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Oncological Urology, Veneto Institute of Oncology IRCCS, Padua, Italy., S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China., Urology Department, Clinique Pasteur, Toulouse, France., Department of Urology, LMU Munich, Germany., Urology Unit, Policlinico Tor Vergata Foundation, Rome, Italy., Division of Urology, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, Torino School of Medicine, Torino, Italy., Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitié-Salpêtrière Hospital, Paris, France., Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France., Department of Urology, University Hospital Zürich, Zürich, Switzerland., Divisions of Urology and Surgical Oncology, Department of Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada., Department of Urology, Marienkrankenhaus Hamburg, Hamburg, Germany., Department of Urology, Helios Hospital, Bad Saarow, Germany; Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg, Germany., Unit of Urology and Renal Transplantation, Oncology Department, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland., Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands., Department of Urology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey., Division of Urology, Department of Surgery, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada., Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele, Milan, Italy., Faculty of Health Sciences and Medicine, University of Lucerne, Switzerland; Clinic for Urology, University Teaching and Research Hospital of the University of Lucerne, Switzerland; Clinic for Urology, Kantonsspital Winterthur, Winterthur, Switzerland; University of Zurich, Zurich, Switzerland.