Adjuvant radiotherapy (ART) post-cystectomy for muscle-invasive bladder cancer sharply cut rates of new pelvic cancer, without adding serious side effects for patients, according to research presented September 29 at the American Society for Radiation Oncology (ASTRO) annual meeting.
Results from the phase III, multicenter randomized Bladder Adjuvant RadioTherapy (BART) trial demonstrated that radiotherapy may be an underused tool for reducing pelvic relapse risk in patients with locally advanced muscle-invasive bladder cancer, noted Vedang Murthy, MD, principal investigator and professor and radiation oncologist at Tata Memorial Hospital in Mumbai, India.
Muscle-invasive bladder cancer is aggressive. Patients typically undergo radical cystectomy -- bladder removal -- and chemotherapy.
Vedang Murthy, MD
"In the last two or three years, they say if you add adjuvant nivolumab for a year, if it's available or affordable, that further moves the needle by six to eight percent, and that's all we've got right now," Murthy said at ASTRO. Even with immunotherapy, most patients still succumb to their disease within 36 months.
Overall survival beyond three years remains low. Distant metastases pose the biggest threat to overall survival, but locoregional occurrences are also a problem, Murthy noted.
"In the last five or seven years there is much more data ... that patients who have certain high-risk features, as given here, higher stage, node positivity, margin positivity, 25% to 30% of patients can have a component of locoregional relapse in the pelvis, and when such pelvic relapses occur it can be quite nasty," Murthy explained. "It is very painful for the patient but also for the treating team."
To determine the benefit of locoregional treatment, the BART trial investigated adjuvant radiotherapy (50.4 Gy in 28 fractions) of stoma and bowel sparing intensity-modulated radiation therapy (IMRT) to pelvic iliac nodes and the cystectomy bed after bladder removal and chemotherapy, against standard observation.
BART followed 153 patients (median age 57) at four centers in India from 2016 to 2024; 63 were analyzed for outcomes in the therapy arm, with 90 analyzed in the observation arm.
"After a median follow-up of 47 months in surviving patients, the two-year locoregional failure-free survival was clinically and statistically significantly better with an absolute improvement of 11%," Murthy explained. "When we looked at this endpoint per protocol, the benefit magnitude was even higher with a hazard ratio of 0.27."
In subgroups, ART also made a big difference, Murthy added, as noted in the results below.
Phase III, multicenter randomized Bladder Adjuvant RadioTherapy (BART) trial conducted in India and presented at ASTRO 2025.Vedang Murthy, MD, via ASTRO 2025
In addition, two-year disease-free survival (DFS) also favored the radiation arm (71.6% vs. 58.7%, p = 0.07). However, rates of distant metastases were similar in both groups, affecting nearly one-third of patients and reflecting the systemic nature of bladder cancer, the results noted.
Modern radiation techniques would be useful as a standard option for high-risk bladder cancer following cystectomy, Murthy's team found. He said the results open avenues for patients who cannot receive or afford immunotherapy.
No patients in the BART trial received immunotherapy; however, Murthy noted that immunotherapy is becoming standard in bladder cancer treatment, and there is “a clear need” to study its use alongside post-operative radiation for patients with high-risk disease.
“The two treatments act differently, with distinct functions and side effect profiles, and there’s no reason we shouldn’t be combining them,” Murthy said prior to ASTRO.
Although the sample size was small in the BART trial, the findings build on a previous study that showed adding IMRT after cystectomy for patients with high-risk, muscle-invasive bladder cancer was safe and caused minimal side effects.
The next step for this research is a prospective meta-analysis combining BART data with large, randomized trials from France and Egypt to further assess safety and benefit in survival outcomes, according to Murthy. However, at ASTRO he also said the time may be right to consider a trial in the U.S.
