Patients with muscle-invasive bladder cancer (MIBC) remain at substantial risk of locoregional recurrence even after radical cystectomy and perioperative chemotherapy. While systemic treatment has evolved significantly in recent years, the role of adjuvant radiotherapy after surgery has remained uncertain because of concerns regarding toxicity and limited prospective evidence.
A recently published phase III randomized trial explored whether adjuvant pelvic radiotherapy could improve outcomes in patients with high-risk urothelial MIBC following cystectomy and chemotherapy.
The study, “Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer,” was published in the Journal of Clinical Oncology on May 21, 2026.
Authors: Vedang Murthy, Priyamvada Maitre, Mahendra Pal, Amandeep Arora, Reena Phurailatpam, Rakesh Sharma, Deleep Gudipudi, Senthil Rajappa, Lincoln Pujari, Bhavesh Bandekar, Deepa Joseph, Sadhana Kannan, Rahul Krishnatry, Ankit Misra, Amit Joshi, Vanita Noronha, Kumar Prabhash, Santosh Menon, Ganesh Bakshi, and Gagan Prakash.
Background
According to the American Cancer Society, bladder cancer remains a major public health concern in the United States. In 2026, an estimated 84,530 new cases are expected, including 64,730 in men and 19,800 in women. The disease is also projected to cause approximately 17,870 deaths, with men accounting for the majority of cases and deaths.
Bladder cancer is more common in men than in women. Smoking remains the most important risk factor, while occupational exposure to certain chemicals, long-term catheter use, and congenital bladder defects may also increase risk. Although incidence rates have declined by about 1% per year in recent years, bladder cancer remains the 10th leading cause of cancer death in the United States.
Read more about Bladder Cancer on OncoDaily.
Study Design and Patient Population
This multicenter phase III randomized trial enrolled patients with nonmetastatic urothelial MIBC considered at high risk of recurrence after radical cystectomy. High-risk features included pT3–T4 disease, nodal involvement, positive surgical margins, or 10 or fewer lymph nodes dissected.
Participants were randomized 1:1 to receive either:
- Adjuvant radiotherapy, or
- Observation alone after surgery.
Patients were stratified according to nodal involvement and the use of perioperative chemotherapy. Radiotherapy consisted of stoma-sparing image-guided intensity-modulated radiotherapy (IG-IMRT) delivered to the cystectomy bed and pelvic lymph nodes at a dose of 50.4 Gy in 28 fractions.
The primary endpoint was 2-year locoregional recurrence-free survival (LRFS), while secondary endpoints included disease-free survival (DFS), bladder cancer–specific survival (BCSS), and overall survival (OS).
Key Findings
Between June 2016 and May 2024, 153 patients were enrolled, with 76 assigned to observation and 77 to adjuvant radiotherapy. Most patients had advanced pathological disease, with 62% presenting with pT3–T4 tumors and 41% having node-positive disease. More than 90% received systemic chemotherapy, predominantly in the neoadjuvant setting, while none received immunotherapy.
After a median follow-up of 47 months, adjuvant radiotherapy significantly improved locoregional control:
- 2-year LRFS: 87.1% with radiotherapy vs 76.0% with observation
- Hazard ratio: 0.43
- P = .04
Additional efficacy outcomes also numerically favored radiotherapy:
- DFS: 71.6% vs 58.7%
- BCSS: 79.6% vs 65.0%
- OS: 70.4% vs 57.4%
Although improvements in DFS, BCSS, and OS did not reach statistical significance, these endpoints numerically favored adjuvant radiotherapy.
Read more about Radiotherapy for Bladder Cancer on OncoDaily.
Safety and Clinical Implications
An important aspect of the trial was the use of modern IG-IMRT techniques, which allowed treatment delivery while minimizing toxicity concerns historically associated with pelvic radiotherapy after cystectomy. The study reported no additional severe toxicity with adjuvant radiotherapy.
These findings suggest a potential role for postoperative pelvic radiotherapy in carefully selected patients with high-risk urothelial MIBC, particularly those with locally advanced disease or nodal involvement after cystectomy.
Conclusion
This phase III randomized trial demonstrated that adjuvant pelvic radiotherapy after radical cystectomy and perioperative chemotherapy improved locoregional recurrence-free survival in patients with high-risk muscle-invasive bladder cancer, without adding severe toxicity.
The study adds prospective evidence supporting the integration of modern adjuvant radiotherapy strategies into multidisciplinary management for selected high-risk patients following cystectomy.
The full article is available on the Journal of Clinical Oncology.