A second transurethral resection of bladder tumour (Re-TURBT) is recommended by European Association of Urology (EAU) Guidelines on non-muscle-invasive bladder cancers (NMIBCs) due to the risk of understaging and/or persistent disease following the primary resection. However, in many cases this may be unnecessary, potentially harmful, and significantly expensive constituting overtreatment. The CUT-less trial aims to combine the preoperative staging accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) and the intraoperative enhanced ability of photodynamic diagnosis (PDD) to overcome the primary TURBT pitfalls thus potentially re-defining criteria for Re-TURBT indications.
Single-centre, non-inferiority, phase IV, open-label, randomised controlled trial with 1:1 ratio.
The primary endpoint is short-term BC recurrence between the study arms to assess whether patients preoperatively categorised as VI-RADS Score 1 and/or Score 2 (i.e., very-low and low likelihood of MIBC) could safely avoid Re-TURBT by undergoing primary PDD-TURBT. Secondary endpoints include mid- and long-term BC recurrences and progression (i-ii). Also, health-related quality of life (HRQoL) outcomes (iii) and health-economic cost-benefit analysis (iv) will be performed.
All patients will undergo preoperative Multiparametric Magnetic Resonance Imaging of the bladder with VI-RADS score determination. A total of 327 patients with intermediate-/high-risk NMIBCs, candidate for Re-TURBT according to EAU Guidelines, will be enrolled over a 3-year period. Participants will be randomised (1:1 ratio) to either standard of care (SoC), comprising primary white-light (WL) TURBT followed by second WL Re-TURBT; or the Experimental arm, comprising primary PDD-TURBT and omitting Re-TURBT. Both groups will receive adjuvant intravesical therapy and surveillance according to risk-adjusted schedules. Measure of the primary outcome will be the relative proportion of BC recurrences between the SoC and Experimental arms within 4.5 months (i.e., any 'early' recurrence detected at first follow-up cystoscopy). Secondary outcomes measures will be the relative proportion of late BC recurrences and/or BC progression detected after 4.5 months follow-up. Additionally, we will compute the HRQoL variation from NMIBC questionnaires modelled over a patient lifetime horizon and the health-economic analyses including a short-term cost-benefit assessment of incremental costs per Re-TURBT avoided and a longer-term cost-utility per quality-adjusted life year gained using 2-year clinical outcomes to drive a lifetime model across the two arms of treatment.
ClinicalTrial.gov identifier (ID): NCT05962541; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) ID: 2023-507307-64-00.
BJU international. 2024 Oct 13 [Epub ahead of print]
Francesco Del Giudice, Annarita Vestri, Danilo Alunni Fegatelli, Tanja Hüsch, Jonathan Belsey, Rajesh Nair, Eila C Skinner, Benjamin I Chung, Martina Pecoraro, Alessandro Sciarra, Giorgio Franco, Benjamin Pradere, Paola Gazzaniga, Fabio Massimo Magloicca, Valeria Panebianco, Ettore De Berardinis
Department of Maternal Infant and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy., Department of Public Health and Infectious Disease, "Sapienza" University of Rome, Rome, Italy., Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy., Clinical development and Medical Affairs, Photocure, ASA, Oslo, Norway., JB Medical Ltd, London, UK., Guy's and St. Thomas' NHS Foundation Trust, Guys Hospital, London, UK., Department of Urology, Stanford University School of Medicine, Stanford, CA, USA., Department of Radiology, Oncology and Pathology, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy., Department of Urology, La Croix Du Sud Hospital, Quint Fonsegrives, France., Department of Molecular Medicine, "Liquid Biopsy" Unit, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy.