Following cystectomy, patients with muscle-invasive bladder cancer at high risk for recurrence may safely be treated with radiotherapy and may achieve an improvement in locoregional control compared with observation. These findings, which come from the phase III BART trial presented in a plenary session during the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting,1 may assuage concerns over radiotherapy to the pelvis after cystectomy and provide an improvement over chemotherapy for locoregional recurrences.
“I hope this trial will allay some of the fears that our radiation oncology community and urosurgeons may have regarding the adverse effects that [adjuvant radiotherapy] may have,” said lead author Vedang Murthy, MD, Professor and Radiation Oncologist at Tata Memorial Hospital in Mumbai, India. “It is relatively safe using modern techniques, and very excitingly this opens up opportunities, including integrating it with immunotherapy, as they have nonoverlapping toxicities.”
Background
Patients with advanced bladder cancer are typically treated with cystectomy and neoadjuvant or adjuvant chemotherapy or adjuvant immunotherapy, though both systemic treatment options provide nominal survival benefits. Then patients are typically followed until their disease recurs.
When patients do recur, it is expected to be a distant failure after surgery. The problem of locoregional recurrences is not as well understood as that of distant disease failures. These locoregional recurrences, which occur in about 30% of patients, can be painful in the pelvis and difficult to manage.2 According to Dr. Murthy, locoregional recurrence requires a local modality, such as radiation therapy.
I hope this trial will allay some of the fears that our radiation oncology community and urosurgeons may have regarding the adverse effects that [adjuvant radiotherapy] may have.— VEDANG MURTHY, MD
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Chemotherapy typically makes little difference difference in reducing local-regional failures, even though it can improve overall survival. The long-term results of the BA06 30894 trial showed neoadjuvant chemotherapy with cisplatin, methotrexate, and vinblastine led to an improvement in 10-year overall survival in muscle-invasive bladder cancer from 30% to 36% (hazard ratio [HR] = 0.84; 95% confidence interval [CI] = 0.72–0.99; P = .037).3
About the BART Trial
The phase III BART study is a multicenter, randomized controlled trial that was conducted in four centers in India. It enrolled 153 patients with muscle-invasive bladder cancer and high-risk pathologic features who were treated with radical cystectomy and chemotherapy. They were randomly assigned to receive either observation or adjuvant radiation therapy of 50.4 Gy in 28 fractions to the pelvic nodes and cystectomy bed. Radiotherapy contouring was conducted in accordance with consensus guidelines from 2016.4 The primary endpoint was the 2-year rate of locoregional failure–free survival.
Patients had a median age of 57 years and a median of 20 nodes dissected. Of note, the majority of patients had T3 or T4 disease (77.1%), pure urothelial histology (72.5%), and received chemotherapy in the neoadjuvant setting (70.6%). One-third of patients had clinically node-positive disease, and 41.2% had pathologic node-positive disease.
Efficacy Findings and Safety
At a median follow-up of 47 months, overall, 28 patients (18%) had a locoregional recurrence. The 2-year locoregional failure–free survival rate was 87.1% with radiation vs 76.0% with observation (HR = 0.43; 95% CI = 0.20–0.96; P = .04). “The 2-year locoregional failure–free survival was clinically and statistically significantly better, with an absolute improvement of 11%,” Dr. Murthy said. In the per-protocol population, the 2-year locoregional failure–free survival rate was 93.2% with radiation and 75.0% with observation (HR = 0.27; 95% CI = 0.10–0.71; P = .008).
The 2-year disease-free survival rate in the radiation arm was 71.6% vs 58.7% in the observation arm (HR = 0.62; 95% CI = 0.36–1.05; P = .07). The rate of bladder cancer–specific survival at 2 years was 79.6% with radiation vs 65.0% with observation (HR = 0.59; 95% CI = 0.33–1.10; P = .09), and overall survival rates were 70.4% and 57.4% with radiation and observation, respectively (HR = 0.78; 95% CI = 0.49–1.26; P = .31).
Patterns of recurrence in the two arms showed no cases of isolated locoregional recurrence with radiation therapy. Distant recurrences occurred in 32% of patients given radiation therapy vs in 30% of patients in the observation arm.
The findings of acute and late toxicity from the BART trial were previously presented and published; the rate of grade 3 or higher adverse effects was 1.6% with radiation vs 4.1% with observation. Grade 2 adverse effects were reported in 17.5% of patients in the radiation therapy arm compared with in 1.4% of the observation arm. Rates of late severe effects were similar between the two arms at 8.4% and 10.5% for radiation and observation, respectively.5 No treatment discontinuations were required due to toxicity.
DISCLOSURE: The study was supported by funding from Tata Memorial Centre. Dr. Murthy reported no conflicts of interest.
REFERENCES
1. Murthy V, et al: 2025 ASTRO Annual Meeting. Abstract PL 01. Presented September 29, 2025.
2. Murthy V, et al: Urol Oncol 39:496.e9-496.e15, 2021.
3. International Collaboration of Trialists, et al: J Clin Oncol 29:2171-2177, 2011.
4. Baumann BC, et al: Int J Radiat Oncol Biol Phys 96:78-86, 2016.
5. Murthy V, et al: Int J Radiat Oncol Biol Phys 121:728-736, 2025.
EXPERT POINT OF VIEW
The invited discussant of the BART trial was Brian C. Baumann, MD, Radiation Oncology, Springfield Clinic Cancer Center in Springfield, Illinois, and Adjunct Assistant Professor of Radiation Oncology at the University of Pennsylvania. For patients with locally advanced bladder cancer, locoregional failure rates after radical cystectomy for those with pT3 to pT4 N0 or N-positive disease range from 20% to 41% at 5 years, he said.1 When patients do experience locoregional failure, morbidity and mortality rates are high.
“These local failures, when they happen, are rarely salvageable,” he commented. “Salvage radiotherapy to curative doses is often precluded because of the proximity to the small bowel in the absence of the bladder.”
Growing Interest in Adjuvant Radiotherapy
Dr. Baumann explained that interest in this setting for adjuvant radiotherapy has been growing over the past 10 years because of a greater recognition of the problem of locoregional failures as well as the potential of newer radiation approaches to reduce adverse effects.2 In an Egyptian randomized phase II study of adjuvant chemoradiation vs chemotherapy alone for patients with locally advanced bladder cancer after radical cystectomy, the addition of radiotherapy improved local control significantly, with a 2-year local recurrence–free survival rate of 96% with radiation vs 69% without (P < .01). In patients with urothelial carcinoma specifically, the rate was 100% with chemoradiation vs 67% with chemotherapy alone (P < .01).3
Brian C. Baumann, MD
Modern randomized trials of adjuvant radiotherapy for locally advanced bladder cancer include the NRG GU-001 trial in the United States, which closed early due to poor accrual; the ongoing French GETUG-AFU-30 trial; a recently completed Egyptian study of 122 patients with locally advanced urothelial carcinoma of the bladder treated with radical cystectomy who were randomly assigned to observation or adjuvant radiation to 50 Gy in 25 fractionsthat showed an improvement in 3-year locoregional recurrence–free survival rates with adjuvant radiation [81% vs 71% (P = .0457)]4; and the BART trial. “Now, BART is the largest of several modern trials to report a significant improvement in local control with adjuvant radiation.”
BART Trial Highlights
Dr. Baumann commended the BART study authors for the inclusion of the cystectomy bed from the start of the trial, even though the consensus contouring guidelines originally recommended omitting it in those with negative surgical margins.4 This was updated in the 2022 guidelines to include the cystectomy bed for all patients.5 “Now, we have very high-quality data showing that adjuvant radiation to the pelvic nodes and the cystectomy bed with intensity-modulated radiation therapy is well tolerated,” he said.
When looking at the locoregional benefit across the patient subgroups, Dr. Baumann highlighted the patients with node-positive disease especially. “There was some controversy as to whether these patients would actually benefit from adjuvant radiation because of the high competing risk of distant failure. But, in fact, we’re seeing that the patients who are node-positive and even the patients at highest risk, both T3 and node-positive, were clearly benefiting from the addition of this treatment,” he said.
He also recommended that these patients receive chemotherapy to address distant disease risk. “My hypothesis here is that adjuvant radiation and perioperative chemotherapy are acting synergistically,” Dr. Baumann commented.
The improved local control for patients translated into improved disease-free survival with the addition of adjuvant radiation therapy, though the difference was not statistically significant. “The BART trial shows a strong trend toward improvement in disease-free survival when you add radiation to a cohort heavily treated with chemotherapy, even though the trial was not powered for this endpoint,” he said.
As the patients in the trial were treated before immunotherapy became available, survival rates are about similar to those of the large adjuvant immunotherapy trials for patients with bladder cancer, in terms of hazard ratios. “Radiation is a promising and potentially cost-effective option for optimal outcomes. The future is probably combining the two,” Dr. Baumann commented. In fact, early results from the phase III SWOG/NRG 1806 (INTACT) trial showed safety with concurrent chemoradiotherapy and atezolizumab for patients with localized muscle-invasive bladder cancer.6
“The BART trial showing this strong improvement in local recurrence–free survival and hazard ratio on disease-free survival that approximates immunotherapy argues that it should also be considered a new standard of care along with adjuvant immunotherapy for many patients,” Dr. Baumann concluded.
DISCLOSURE: Dr. Baumann has reported consulting with Boston Scientific, Varian, Novartis, and Blue Earth Diagnostics, outside of the scope of the current project.
REFERENCES
1. Christodouleas JP, Baumann BC, He J, et al: Optimizing bladder cancer locoregional failure risk stratification after radical cystectomy using SWOG 8710. Cancer 120:1272-1280, 2014.
2. Baumann BC, Efstathiou JA: Adjuvant radiation therapy for locally advanced bladder cancer. Int J Radiat Oncol Biol Phys 121:737-740, 2025.
3. Zaghloul MS, Christodouleas JP, Smith A, et al: Adjuvant sandwich chemotherapy plus radiotherapy vs adjuvant chemotherapy alone for locally advanced bladder cancer after radical cystectomy. JAMA Surg 153:e174591, 2018.
4. Zaghloul MS, Alnagmy AK, Kasem HA, et al: The value and safety of adjuvant radiation therapy after radical cystectomy in locally advanced urothelial bladder cancer. Int J Radiat Oncol Biol Phys 120:658-666, 2024.
5. Verghote F, Sargos P, Christodouleas JP, et al: International consensus guidelines for adjuvant radiation therapy for bladder cancer after radical cystectomy. Pract Radiat Oncol 12:524-532, 2022.
6. Singh P, Efstathiou JA, Tangen C, et al: INTACT (S/N1806) phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle-invasive bladder cancer. 2021 Genitourinary Cancers Symposium. Abstract 428.
