Inside the POTOMAC Trial: Durvalumab Plus BCG for High-Risk NMIBC

In this installment, Chandler Park, MD, opens by crediting Neal D. Shore, MD, FACS, as one of the main investigators behind landmark trials in BCG-naïve NMIBC, and argues that immunotherapy alongside BCG offers a first shot for these patients. He notes that urologists, like oncologists, build long-term relationships with patients and should be equipped to have that shared decision-making conversation.

He then asks Shore how he is currently sequencing therapy after transurethral resection of the bladder tumor for patients with high-risk NMIBC. Shore explains that before POTOMAC (NCT03528694), community physicians rarely moved a high-risk patient, one with T1 disease, lamina propria invasion, or multifocal carcinoma in situ, straight to cystectomy; most preferred bladder-preserving induction BCG for at least 5 of 6 planned weekly instillations, followed by maintenance. However, ongoing BCG shortages in the US and abroad have challenged this approach.

Shore walks through the scientific rationale behind combining BCG with immunotherapy, noting that preclinical data showed that BCG administration upregulates PD receptors, suggesting a checkpoint inhibitor given concomitantly with BCG could improve outcomes.

Shore details the trial design of POTOMAC, a global, 3-arm study in which patients received durvalumab plus BCG induction and maintenance for 1 year (monthly IV dosing every 4 weeks) in 1 arm, compared against a key comparator arm of BCG induction and maintenance alone, plus a third arm receiving durvalumab with BCG induction only, without maintenance.

POTOMAC hit its primary end point with a hazard ratio of 0.68 for disease-free survival, favoring the durvalumab-plus-BCG combination. These data, were first presented at ESMO 2025 and published in The Lancet, and led to FDA approval of the combination in May 2026.

In the next episode, "Managing Immune-Related Adverse Events With Durvalumab Plus BCG in NMIBC," Park reacts to the size of the DFS benefit, then shifts the conversation to the immune-related adverse events community urologists need to understand.