Bladder-preserving concurrent radiotherapy and low-dose gemcitabine for muscle-invasive bladder urothelial carcinoma: Pathological complete response and safety

Purpose Muscle-invasive bladder urothelial carcinoma (MIBUC) is an aggressive disease requiring multimodal management, and optimizing bladder-preserving chemoradiotherapy remains a clinical priority. This research aimed to compare the effectiveness and safety of radiotherapy alone versus low-dose gemcitabine plus radiotherapy (LD-Gem-RT) for treating individuals diagnosed with MIBUC. Methods This retrospective investigation included individuals diagnosed with non-metastatic MIBUC treated at a single institution between May 2020 and December 2023. Participants were stratified into a radiotherapy-alone (RT) group and a LD-Gem-RT group based on post-TURBT treatment. Clinical and pathological complete response (cCR/pCR) were evaluated 4–6 weeks after induction radiotherapy. Two-year outcomes including bladder-intact distant metastasis-free survival (BI-DMFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed. The median follow-up for the entire cohort was 26 months (IQR: 22–32 months); 12 patients (8.00%) were censored before 24 months due to loss to follow-up (n = 5) or competing mortality (n = 7). Adverse events were graded per CTCAE v5.0, while quality of life was assessed at baseline and after 12 months. Results The study cohort comprised 150 patients, of which 79 were treated solely with RT and 71 received LD-Gem-RT. The LD-Gem-RT group exhibited significantly higher cCR (77.46% vs. 58.23%, P = 0.012) and pCR (64.79% vs. 46.84%, P = 0.027) rates. Two-year BI-DMFS was superior in the LD-Gem-RT group (80.28% vs. 59.49%, P = 0.006), whereas CSS and OS did not differ significantly. Adverse event profiles were similar across both groups, with no notable distinction in overall incidence of early or late toxicity (both P > 0.05). At 12 months, LD-Gem-RT patients reported worse role functioning, fatigue, nausea/vomiting, and diarrhea, but fewer urinary symptoms and better body image (all P < 0.05). Conclusion Concurrent low-dose gemcitabine with radiotherapy improves complete response and bladder-intact distant metastasis-free survival without significantly increasing severe toxicity, supporting its utility in bladder-preserving regimens for MIBUC.