A landmark phase III randomized trial has demonstrated that adjuvant radiation therapy following radical cystectomy significantly reduces pelvic recurrence in patients with high-risk, locally advanced muscle-invasive bladder cancer. The Bladder Adjuvant RadioTherapy (BART) trial, conducted across multiple centers in India, represents one of the largest randomized studies to establish the clinical benefit of post-operative radiation in this challenging patient population.
The study enrolled 153 patients with locally advanced, urothelial muscle-invasive bladder cancer between 2016 and 2024. Participants were randomly assigned to receive either post-operative radiation therapy (50.4 Gy in 28 fractions, n=77) or observation alone (n=76). All patients underwent radical cystectomy, with nearly all receiving chemotherapy either before surgery (71%) or after (20%).
Significant Reduction in Pelvic Recurrence
The trial's primary endpoint showed striking results for locoregional control. Over a median follow-up of 47 months, only 8% of patients in the radiation group experienced locoregional recurrence compared to 26% in the observation group (p=0.006). Two-year locoregional recurrence-free survival reached 91.2% with radiation therapy versus 76.4% without treatment (p=0.004).
"This is one of the first studies and the largest randomized trial to show that post-operative radiation therapy can meaningfully reduce pelvic relapses in bladder cancer," said Dr. Vedang Murthy, principal investigator and professor at Tata Memorial Hospital in Mumbai. "Pelvic relapse can be devastating for patients – extremely painful and almost impossible to treat."
High-Risk Patient Population
The study population represented patients at substantial risk for recurrence. Among participants, 62% had tumors extending outside the bladder wall (pT3–T4), 41% showed lymph node involvement (pN+), and 28% displayed variant tumor subtypes. This high-risk profile underscores the clinical significance of the observed benefits.
Disease-free survival also favored the radiation arm, with rates of 77.6% versus 64.4% in the observation group (p=0.07). However, distant metastases occurred at similar rates in both groups, affecting nearly one-third of patients and reflecting the systemic nature of advanced bladder cancer.
Safety Profile and Tolerability
The safety analysis revealed reassuring toxicity profiles. Severe late side effects occurred in 8.5% of patients receiving radiation compared to 10.5% in the observation arm (p=0.6). This finding challenges historical concerns about radiation-related complications in the pelvic region following cystectomy.
"BART shows that modern radiation techniques allow us to deliver highly targeted treatment with fewer complications than in the past," Dr. Murthy explained. "Radiation therapy is already used safely after surgery for gynecologic cancers in the same anatomically complex region, suggesting it could also become a standard option for high-risk bladder cancer following cystectomy."
Survival Outcomes and Future Directions
Two-year overall survival was higher in the radiation arm at 68% versus 57%, though this difference did not reach statistical significance (p=0.4). Dr. Murthy attributed this to the study's sample size and noted that his team plans a prospective meta-analysis combining BART data with large randomized trials from France and Egypt to further assess survival benefits.
Subgroup analyses revealed additional insights, suggesting particular benefit from radiation therapy for patients with larger tumors (T3-4) and node-positive disease. These findings point toward potential personalized treatment approaches for high-risk bladder cancer patients.
The study addresses a critical unmet need in bladder cancer management. Each year, approximately 20,000 to 25,000 people in the United States and more than half a million worldwide are diagnosed with muscle-invasive disease. Despite standard treatment with radical cystectomy and chemotherapy, up to one-third develop new pelvic tumors within two to three years.
"Bladder cancer is aggressive, and surgery and chemotherapy alone are not enough to prevent pelvic recurrence," Dr. Murthy noted. "But in our trial, very few people who received radiation had a locoregional relapse within two years."
The findings were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting and represent a potential paradigm shift in post-operative management for high-risk bladder cancer patients.
