In 14 months, the US Food and Drug Administration (FDA) approved the antibody durvalumab (trade name Imfinzi, manufacturer AstraZeneca) twice for bladder cancer: in March 2025 for invasive stage disease and in May 2026 for early non-invasive stage disease. Together, these approvals cover the two main forms of the disease and could fundamentally change the treatment standard.
Bladder cancer globally: Common, often in older age
Bladder cancer is among the most common cancers worldwide. The disease occurs in two main forms: invasive muscle-invasive bladder cancer (MIBC), which has penetrated the bladder muscle, and non-muscle-invasive bladder cancer (NMIBC), confined to the inner lining. These two forms demand fundamentally different treatments. NMIBC is typically managed by instilling the immune stimulant BCG, an attenuated tuberculosis bacterium, into the bladder. MIBC requires more aggressive treatment and in most cases radical cystectomy, surgical removal of the bladder.
Immunotherapy represents a new approach to both forms. Durvalumab belongs to the class of PD-L1 inhibitors, which block a surface protein on tumor cells that suppresses the immune system. When PD-L1 is blocked, T-cells can recognize and attack the tumor.
NIAGARA: The first breakthrough in invasive disease
The NIAGARA trial (NCT03732677) was a randomized Phase 3 study with 1,063 patients with muscle-invasive bladder cancer. Researchers compared neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by radical cystectomy with the same regimen plus durvalumab, followed by durvalumab as adjuvant maintenance therapy. Results published in the New England Journal of Medicine in November 2024 showed two-year disease-free survival in 67.8 percent of durvalumab patients versus 59.8 percent in the control group (hazard ratio 0.68). This corresponds to a 32 percent reduction in recurrence risk. Two-year overall survival was 82.2 percent with durvalumab versus 75.2 percent without (HR 0.75). The FDA granted approval on March 28, 2025.
POTOMAC: Addition in early-stage disease
The POTOMAC trial (NCT03528694) studied 1,018 patients with BCG-naive high-risk NMIBC. Researchers compared BCG induction and maintenance therapy alone with the same regimen plus durvalumab. After a median follow-up of 72 months, five-year overall survival was 88 percent with durvalumab versus 86 percent without. The recurrence and death risks were reduced by 32 percent over a median observation period of 60.7 months. The absolute survival benefit was more modest than in NIAGARA. The FDA approved the combination on May 28, 2026.
Oncologists are debating whether the modest absolute survival difference of two percentage points, given already high baseline survival, justifies routine addition of durvalumab. The European Association of Urology (EAU) has not yet updated its guidelines for NMIBC stage based on these new data. Professional societies emphasize that guideline updates take time before therapy recommendations reach clinicians.
In comparison: How immunotherapies changed other cancers
Other PD-L1 inhibitors have fundamentally changed cancer treatment over the past decade. The PD-1 inhibitor pembrolizumab (Keytruda, Merck) raised five-year survival in advanced melanoma from under 10 percent to over 30 percent. Nivolumab (Opdivo, Bristol Myers Squibb) achieved similar progress in non-small cell lung cancer. For bladder cancer, durvalumab is the first PD-L1 inhibitor with approval for both main disease stages. AstraZeneca confirmed that Imfinzi is thereby the first and only perioperative immunotherapy for muscle-invasive bladder cancer.
What remains inaccessible for many patients
The NIAGARA trial enrolled only cisplatin-eligible patients. About 20 to 30 percent of muscle-invasive bladder cancer patients are deemed cisplatin-ineligible, often due to reduced kidney function, which is common in older age. This group receives no direct benefit from NIAGARA. For older patients who are candidates for neither cisplatin-based chemotherapy nor radical cystectomy, bladder-preserving approaches are being researched. The RAD-IO trial, combining durvalumab with chemoradiation instead of surgery, presented early feasibility data at the ASCO 2026 meeting. Final efficacy data for this approach are still pending. The price access question also remains open for durvalumab: immunotherapies typically cost several thousand euros monthly, a significant barrier outside well-insured health systems.
Until guideline adoption in Europe: What matters now
The next crucial step is updating European guidelines by EAU and ESMO, which govern clinical practice outside the US. This process typically takes one to two years following FDA approval. In parallel, the RAD-IO trial continues, aiming to establish bladder preservation through chemoradiation plus immunotherapy as an equivalent alternative to cystectomy. If this trial succeeds, treatment options for patients wishing to preserve their bladder could fundamentally improve. Timeline: final results expected by 2028 at the earliest.