Online Adaptive Radiotherapy for Bladder Preservation: Transitioning to Hypofractionation.

Abstract

Purpose: To present the clinical experience of bladder preservation with adaptive radiotherapy (ART) in conventionally fractionated RT (ConvRT) and discuss the challenges in transitioning to hypofractionated RT (HypoRT) METHODS AND MATERIALS: Consecutive patients from a prospectively maintained institutional database with histologically proven urothelial carcinoma, staged T1-T4, N0-N3, M0, treated with curative intent chemoradiotherapy from January 2014 to December 2023 were included. Patients from 2014 were treated with a dose of 64Gy/32# to the bladder and 55Gy/32# to the pelvis. From 2021 onwards, most patients received 55Gy/20# to the bladder and 44Gy/20# to the pelvis. Suitable patients received neoadjuvant and concurrent chemotherapy. All patients were treated with the "plan of the day" adaptive radiotherapy (POD-ART) technique. Acute (within 3 months of radiotherapy) and late urinary and gastrointestinal toxicity were assessed using the CTCAE criteria. Overall survival (OS), bladder cancer-specific survival (BCSS), disease-free survival (DFS) and local control (LC) were analysed.

Results: About 221 patients treated with POD-ART were analysed, 146 with ConvRT and 75 with HypoRT. Most treatment and clinical characteristics were comparable between groups. In HypoRT, the gemcitabine dose was capped at 75 mg/m². Acute GU toxicity rates were similar between ConvRT and Hypo RT cohorts. Acute Grade 2 GI toxicity was higher in the Hypo RT cohort (26.7%) compared to the Conv RT cohort (13.7%, p = 0.02). There were no ≥Grade 3 acute GU or GI toxicity in the Hypo RT cohort. On multivariable analysis, age > 60 years and use of concurrent gemcitabine were statistically significant for acute ≥Grade 2 GI toxicity. Late GU and GI toxicity rates at 15 months were similar in both cohorts. The 2-year OS, BCSS, DFS, and LC rates of patients in the ConvRT cohort were 85.9% (95% CI: 79.6% - 92.1%), 88.2% (95% CI: 82.3% - 94.0%), 83.4% (95% CI: 76.7% - 90.0%) and 89.0% (95% CI: 83.3% - 94.6%) and HypoRT cohort was 85.3% (95% CI: 74.7% - 95.8%), 90.2% (95% CI: 80.7% - 99.6%), 80.4% (95% CI: 69.6% - 91.1%) and 89.6% (95% CI: 81.3% - 97.8%) respectively.

Conclusion: POD-ART allows safe treatment transition from ConvRT to HypoRT for bladder preservation. It mitigates some of the treatment-related toxicity during HypoRT, even with concurrent gemcitabine and pelvic radiotherapy.