Online Adaptive Radiation Therapy for Bladder Preservation: Transitioning to Hypofractionation

To present the clinical experience of bladder preservation with adaptive radiation therapy (ART) in conventionally fractionated radiation therapy (ConvRT) and discuss the challenges in transitioning to hypofractionated radiation therapy (HypoRT).

Consecutive patients from a prospectively maintained institutional database with histologically proven urothelial carcinoma, staged T1 to T4, N0 to N3, M0, treated with curative intent chemoradiation therapy from January 2014 to December 2023 were included. Patients from 2014 were treated with a dose of 64 Gy/32# to the bladder and 55 Gy/32# to the pelvis. From 2021 onward, most patients received 55 Gy/20# to the bladder and 44 Gy/20# to the pelvis. Suitable patients received neoadjuvant and concurrent chemotherapy. All patients were treated with the "plan of the day" adaptive radiation therapy (POD-ART) technique. Acute (within 3 months of radiation therapy) and late urinary and gastrointestinal (GI) toxicity were assessed using the common terminology criteria for adverse events. Overall survival (OS), bladder cancer-specific survival (BCSS), disease-free survival (DFS), and local control (LC) were analyzed.

A total of 221 patients treated with POD-ART were analyzed, 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 genitourinary (GU) toxicity rates were similar between ConvRT and HypoRT cohorts. Acute grade 2 GI toxicity was higher in the HypoRT cohort (26.7%) compared with the ConvRT cohort (13.7%; P = .02). There were no ≥grade 3 acute GU or GI toxicity in the HypoRT 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% confidence interval [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.

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 radiation therapy.