Patients with non-muscle-invasive bladder cancer (NMIBC) have a significant risk of recurrence after trans-urethral resection of bladder tumor (TURBT). The use of neoadjuvant intravesical therapy prior to TURBT has been investigated previously as a possible treatment alternative, but the prospective evidence remains fragmented and heterogeneous.
This systematic review and meta-analysis aimed to synthesize the literature and assess whether outcomes differ compared with upfront TURBT.
We performed a comprehensive search in PubMed, Scopus, Embase, and Web of Science for prospective studies investigating recurrence-free survival (RFS) among patients with primary or recurrent NMIBC who received neoadjuvant intravesical treatment before TURBT. Only studies with an interventional treatment arm that used neoadjuvant treatment with subsequent TURBT were included in the meta-analysis. Cochrane Q test was used to assess heterogeneity of estimates across studies.
Overall, eight studies were eligible for systematic review and six for meta-analysis with RFS as outcome. Estimates of 1-, 2- and 3-yr RFS were 96% (Confidence Interval [CI]: 92-100%), 82% (95% CI: 60-100%), and 77% (95% CI: 56-97%) for patients who received any neoadjuvant treatment (intravesical mitomycin C [MMC], electromotive drug administration MMC, and hyperthermic intravesical chemotherapy MMC) followed by TURBT, whereas for patients who received upfront TURBT the 1-, 2- and 3-yr RFS estimates were 76% (95% CI: 61-91%), 55% (95% CI: 32-77%), and 54% (95% CI: 31-78%), respectively. The use of neoadjuvant intravesical therapy provided benefit in terms of RFS compared with upfront TURBT (Hazard Ratio: 0.42, 95% CI: 0.29-0.61, p < 0.001). No grade 3-5 adverse events (AEs) were observed in patients treated with neoadjuvant intravesical therapy across different studies.
The use of neoadjuvant intravesical therapy before TURBT results in higher short-term RFS compared with upfront TURBT in patients with NMIBC without causing grade 3-5 AEs. These findings support the need for adequately powered randomized trials to define patient selection, optimal regimens, and the durability of any observed benefit before routine clinical adoption.
European urology oncology. 2026 May 12 [Epub ahead of print]
Paolo Zaurito, Pietro Scilipoti, Alfonso Santangelo, Alison Birtle, Lydia Makaroff, Eva Compérat, José L Dominguez-Escrig, Fredrik Liedberg, Paramananthan Mariappan, Alexandra Masson-Leconmte, Jeremy Yuen-Chun Teoh, Benjamin Pradere, Bhavan P Rai, Bas W G van Rhijn, Thomas Seisen, Shahrokh F Shariat, David D'Andrea, Francesco Soria, Robert Wood, Evanguelos Xylinas, Francesco Montorsi, Alberto Briganti, Paolo Gontero, Marco Moschini, European Association of Urology (EAU) Guidelines Panel on Non-muscle-invasive Bladder Cancer
Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK., Fight Bladder Cancer, Chinnor, UK; World Bladder Cancer Patient Coalition, Brussels, Belgium., Department of Pathology, Medical University of Vienna, Vienna, Austria., Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Institute of Translational Medicine, Lund University, Malmö, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden., Edinburgh Bladder Cancer Surgery (EBCS), Western General Hospital, The University of Edinburgh, Edinburgh, UK., Department of Urology, AP-HP, Saint Louis Hospital, Université de Paris, Paris, France., S.H. Ho Urology Centre, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China., Department of Urology, La Croix Du Sud Hospital, Quint Fonsegrives, France., Department of Urology, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Urology, GRC 5 Predictive Onco-Uro, AP-HP, Pitie-Salpetriere Hospital, Sorbonne University, Paris, France., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University Vienna, Vienna, Austria., Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., EAU Guidelines Office, Arnhem, The Netherlands., Department of Urology, Bichat-Claude Bernard Hospital, AP-HP, Université de Paris, Paris, France., Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: .