Adjuvant radiation therapy following radical cystectomy and chemotherapy was found to be safe and efficacious for patients with locally advanced muscle-invasive bladder cancer, according to findings from the phase III randomized BART trial presented at the American Society for Radiation Oncology (ASTRO) 67th Annual Meeting (Abstract 2).
Patients treated with adjuvant radiotherapy experienced improvements in locoregional failure-free survival and disease-free survival without significant severe late toxicities.
“This is one of the first studies and the largest randomized trial to show that postoperative radiation therapy can meaningfully reduce pelvic relapses in bladder cancer,” said principal study investigator Vedang Murthy, MD, Professor and Radiation Oncologist at Tata Memorial Hospital in Mumbai, India. “Pelvic relapse can be devastating for patients—extremely painful and almost impossible to treat. Our research shows that modern radiation therapy offers a safe way to prevent many of these recurrences and improve patients’ quality of life.”
Rationale and Study Methods
Up to one-third of patients undergoing radical cystectomy and chemotherapy can develop new pelvic tumors within 2 to 3 years of treatment. Recurrences in the pelvis can be extremely painful for patients and hard to treat.
The BART trial randomly assigned 153 patients with high-risk, locally advanced urothelial muscle-invasive bladder cancer to receive either adjuvant radiation therapy at 50.4 Gy in 28 fractions or observation. Most patients also received chemotherapy either before or after surgery, but no patients received immunotherapy.
Key Study Findings
Patients were followed for a median of 23 months, at which point 37% had experienced recurrence, including 18% with locoregional recurrences, which consisted of 8% from the radiation arm and 26% from the observation arm (P = .006). “Bladder cancer is aggressive, and surgery and chemotherapy alone are not enough to prevent pelvic recurrence,” said Dr. Murthy. “But in our trial, very few people who received radiation had a locoregional relapse within 2 years.”
The locoregional failure-free survival rate at 2 years was 91.2% in the adjuvant radiation therapy arm compared with 76.4% in the observation arm (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.10‒0.71; P = .004). The disease-free survival rates at 2 years were 59.9% and 52.8% in the radiation and observation arms, respectively (HR = 0.74; 95% CI = 0.47‒1.17; P = .20). Bladder cancer‒specific survival rates were 77.6% at 2 years in the radiation arm vs 64.4% in the observation arm (HR = 0.57; 95% CI = 0.31‒1.07; P = .07).
Competing risk analysis showed that radiation therapy improved locoregional failure-free survival and disease-free survival rates more than observation alone. Subgroup analysis showed benefit with radiation especially in patients with T3-T4 and N+ disease.
At 2 years, the overall survival rate in the adjuvant radiation therapy arm was 68.1% compared with 57.0% in the observation arm (HR = 0.80; 95% CI = 0.49‒1.30; P = .4).
Rates of late grade 3 or higher adverse events were similar between the two arms at 8.5% with radiation and 10.5% with observation (P = .6).
“BART shows that modern radiation techniques allow us to deliver highly targeted treatment with fewer complications than in the past. 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,” Dr. Murthy said.
Disclosure: For full disclosures of the study authors, visit amportal.astro.org.
