Leslie Ballas, MD, highlights trial of risk-adapted bladder preservation in MIBC

In this interview, Leslie K. Ballas, MD, discusses the background and design for the phase 2 BRIGHT trial (NCT07061964), evaluating the effect of giving pembrolizumab (Keytruda) in combination with radiation therapy after chemotherapy in preventing cystectomy in patients with muscle-invasive bladder cancer (MIBC). The design of the study was presented at the 2026 ASCO Genitourinary Cancers Symposium in San Francisco, California.¹

Ballas is a professor of clinical radiation oncology at Cedars-Sinai Medical Center in Los Angeles, California.

Ballas explained that as systemic therapies have improved in recent years, particularly in the neoadjuvant setting, there has been increasing investigation into whether select patients who achieve a clinical complete response (cCR) may be able to safely avoid radical cystectomy. However, prior data from studies such as SWOG 0219 demonstrated that up to 60% of patients with an apparent cCR still had residual disease at the time of surgery, underscoring the continued importance of local therapy even in patients who respond well to systemic treatment.

The BRIGHT trial was designed to build upon earlier phase 2 work evaluating systemic therapy–only approaches in patients who achieve a pathologic complete response following neoadjuvant therapy. In this study, patients with MIBC may receive any standard neoadjuvant regimen, including protocols such as the NIAGARA protocol or enfortumab vedotin plus pembrolizumab prior to undergoing comprehensive restaging with imaging and transurethral resection of bladder tumor (TURBT). Patients who demonstrate a clinically meaningful response (≤cT1 disease) are eligible to proceed with a bladder-preserving approach consisting of radiation therapy combined with immunotherapy. Those with more advanced residual disease are directed toward alternative treatment options, including radical cystectomy or trimodal therapy.

Patients enrolled in the BRIGHT trial are followed with cystoscopy and imaging every 3 months for the first 2 years. The primary end point is 3-year bladder-intact event-free survival. Secondary end points include cystectomy-free survival, overall survival, progression-free survival, distant metastasis–free survival, and treatment-related toxicity, with the goal of determining whether immunoradiotherapy following neoadjuvant therapy can offer a safe and effective bladder preservation strategy in appropriately selected patients.

REFERENCE

1. Ballas LK. SWOG 2427: Single arm phase II study of bladder preservation with immunoradiotherapy after a clinically meaningful response to neoadjuvant therapy in patients with muscle invasive bladder cancer (BRIGHT). J Clin Oncol. 2026;44 (suppl 7; abstr TPS913)