Neoadjuvant Chemotherapy Followed By Conformal Hypofractionated Radiotherapy with Concurrent Gemcitabine in Muscle - Invasive Bladder Cancer

Purpose: The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy (CRT) of weekly gemcitabine with conformal hypofractionated radiotherapy after neoadjuvant chemotherapy.Patients and Methods: Forty patients with transitional cell carcinoma, stage T2-4a, N0, M0 after magnetic resonance imaging were recruited. Transurethral resection was done and neoadjuvant chemotherapy with gemcitabine 1250 mg/m² on days 1 and 8 with cisplatin 100 mg/m2 on day1 repeated every three weeks was given. CRT phase included gemcitabine at 100 mg/m2 on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. The end points were tumor response, toxicity, and survival.Results: Thirty three patients (82.5%) completed treatment protocol. Twenty five patients (75.8%) achieved a complete endoscopic response. The remaining 8 patients (24.2%) had residual disease. At a median follow-up of 23.5 months (range, 11 to 33 months), 19 patients (57.6%) had a functional and intact bladder. Four patients (12.1%) had a loco regional recurrences and 2 patients (6.1%) developed distant metastasis. By using Kaplan-Meier analysis, 2-year disease free survival was 64%, and overall survival was 77.5%. Out of the 33 patients who entered the CCRT phase, only 6 patients (18.2%) had grade 3 acute rectal or bladder toxicity. No one developed G3 late toxicity. Overall, side effects were tolerable and manageable.Conclusion: Concurrent gemcitabine-based CRT after neoadjuvant chemotherapy and TURBT is effective with high response rate, durable local control and acceptable toxicity, which allows patients to preserve their own bladder. However further investigations is needed to confirm these results in larger number in a phase III trial