A phase 3 clinical trial presented at the American Urological Association's 2026 annual meeting found that combining an immunotherapy drug called durvalumab with the standard BCG (bacillus Calmette-Guérin) treatment improved disease-free survival in patients with high-risk non-muscle-invasive bladder cancer (NMIBC), though the benefit came with significantly higher rates of serious side effects.

What Is the POTOMAC Trial and What Did It Show?

The POTOMAC trial enrolled patients with BCG-naive high-risk NMIBC (meaning they had not previously received BCG treatment) and randomly assigned them to receive either BCG induction and maintenance therapy alone, or the same BCG regimen combined with intravenous durvalumab infusions given every 4 weeks for 13 cycles. The study followed patients for more than 5 years, making it one of the longest-running investigations of this combination approach.

At the 4-year mark, patients receiving the combination treatment showed a disease-free survival rate of 80% compared to 75% for those receiving BCG alone. This translates to a meaningful reduction in the risk of disease progression or recurrence. In a subgroup of patients with papillary-only tumors (a specific type of bladder cancer), the benefit was even more pronounced, with 4-year disease-free survival rates of 84% versus 74%.

Beyond survival metrics, the combination approach also reduced early high-risk disease events: 45% of patients in the combination arm experienced these events compared to 61% in the BCG-only group. Additionally, fewer patients progressed to BCG-unresponsive disease (a state where the standard treatment stops working) when durvalumab was added: 65% versus 81%.

Why Are Doctors Concerned About the Side Effects?

Despite the encouraging efficacy signals, the toxicity profile raised significant concerns among the research team. Grade 3 or 4 adverse events (the most serious categories on the medical severity scale) occurred in 21% of patients receiving the combination therapy compared to just 4% in the BCG-only group. This represents a more than fivefold increase in serious side effects.

The most common severe immune-related adverse events included hypothyroidism (an underactive thyroid) and liver toxicities. Notably, approximately one-third of these serious complications had not resolved by the end of the study period, meaning some patients were left with lasting health consequences.

How to Weigh the Benefits and Risks of This Treatment Combination

• Disease Control Gains: The combination improved 4-year disease-free survival by 5 percentage points and reduced progression to BCG-unresponsive disease by 16 percentage points, offering meaningful protection against cancer recurrence.
• Serious Side Effect Risk: Patients choosing the combination approach face a significantly elevated risk of grade 3-4 adverse events, with hypothyroidism and liver damage being the primary concerns, and some complications persisting long-term.
• Overall Survival Question: Despite improved disease-free survival, the trial did not demonstrate a survival advantage after more than 5 years of follow-up, leaving uncertainty about whether the treatment ultimately extends lifespan.
• Cystectomy Rates Unchanged: Both groups had similarly low rates of bladder removal surgery, suggesting the immunotherapy did not meaningfully reduce the need for this more invasive procedure.

The research team noted that BCG delivery was not substantially compromised by the addition of durvalumab; 87% of patients in the combination arm received adequate BCG compared to 93% in the BCG-only arm. This suggests the toxicity increase was not simply due to patients being unable to tolerate the full treatment regimen.

"While the data support improved disease-free survival with the addition of immunotherapy, the absence of a demonstrated overall survival or cystectomy advantage may make the risk-benefit balance difficult for some patients and clinicians to accept," noted researchers analyzing the trial results.

Researchers, American Urological Association 2026 Annual Meeting

The POTOMAC findings highlight a broader challenge in modern oncology: improved intermediate outcomes (like disease-free survival) do not always translate to the ultimate goal of extended lifespan. For patients and their doctors, this means the decision to pursue the combination approach requires careful discussion about personal priorities, tolerance for side effects, and individual cancer characteristics.

The trial results were presented by Dr. Neal Shore at the American Urological Association's 2026 annual meeting in Washington, DC, which brought together leading urologic oncologists to discuss emerging treatment strategies and technologies reshaping cancer care.