Trimodal therapy (TMT) is a viable option for muscle-invasive bladder cancer (MIBC), but the optimal chemotherapy regimen remains unclear. This phase II randomized trial (NCT01495676) compared cisplatin (CDDP) with twice-weekly gemcitabine (GEM) and radiation therapy (RT) with CDDP plus RT.
Patients with pT2-pT3N0M0 MIBC, after macroscopically complete transurethral resection (TURBT), received RT (63 Gy to the bladder, 45 Gy to the pelvis, 1,8 Gy/ fraction) with chemotherapy (CDDP 20 mg/m2/day for 4 days every 21 days alone or plus GEM 25 mg/m2 twice weekly). The primary endpoint was 2-year disease-free survival (DFS); secondary endpoints included overall survival (OS) and toxicities. A 1:2 randomization was planned to include 36 patients in the control arm and 73 patients in the experimental arm.
Sixty-nine patients were included: 24 in the RT/CDDP arm and 45 in the RT/CDDP/GEM arm. The median follow-up was 63 months. Two-year DFS was similar between groups (58.3% CI95% [36.6-77.9] vs. 60.0% CI95% [44.3-74.3]), with median DFS of 29.8 (RT/CDDP) vs. 37.4 (RT/CDDP/GEM) months. OS at 24 and 60 months was 91.3% [IC 95% 69.5-97.8] and 66.8% [IC 95% 39.6-83.9] (RT/CDDP) vs. 66.7% % [IC 95% 50.2 - 78.8] and 53.7% [IC 95% 37.2 - 67.6] (RT/CDDP/GEM). Toxicity profiles were comparable except for increased cytopenias in the GEM arm.
Adding GEM to CDDP did not improve 2-year DFS in MIBC patients treated with TMT. Results should be interpreted cautiously due to early study termination and insufficient accrual.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2026 Feb 12 [Epub ahead of print]
Morgan Michalet, Philippe Ronchin, Thomas Reynaud, Nicolas Demogeot, Sophie Gourgou, Simon Thézenas, Jean-Michel Hannoun-Lévi, Naji Salem, Magali Quivrin, Olivier Riou, Marie Charissoux, Carmen Llacer-Moscardo, Diego Tosi, Catherine Durdux, Nazim Khalladi, Stéphane Culine, David Azria
University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier Cancer Institute (ICM), Univ Montpellier, INSERM U1194 IRCM, Montpellier, France. Electronic address: ., Radiation Oncology, Centre Azuréen de Cancérologie, Mougins, France., Radiation Oncology, CHU Saint-Etienne, Saint-Etienne, France., Radiation Oncology, Institut de cancérologie de lorraine, Nancy, France., Biometrics Unit ICM, Montpellier Cancer Institute, Univ Montpellier, Montpellier, France., Biometrics Unit ICM, Montpellier Cancer Institute, Univ Montpellier, Montpellier, France. Electronic address: ., Radiation Oncology, Centre Antoine Lacassagne, Nice, France., Radiation Oncology, Institut Paoli Calmettes, Marseille, France., Radiation Oncology, Centre Georges-Francois Leclerc, Dijon, France., University Federation of Radiation Oncology of Mediterranean Occitanie, Montpellier Cancer Institute (ICM), Univ Montpellier, INSERM U1194 IRCM, Montpellier, France., Medical Oncology, Montpellier Cancer Institute (ICM), Univ Montpellier, INSERM U1194 IRCM, Montpellier, France., Radiation Oncology, Hopital européen Georges Pompidou, Paris, France., Radiation Oncology, Centre Francois Baclesse, Caen, France., Medical Oncology, Hôpital Saint Louis, Paris, France.