The POTOMAC Trial and FDA Approval: Is Durvalumab Plus BCG a New Standard of Care in High-Risk NMIBC? Expanded AUA 2026 Analyses

KEY FINDINGS

• FDA approval: On 28 May 2026 the FDA approved durvalumab (Imfinzi, AstraZeneca) in combination with BCG induction and maintenance therapy in BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC).
• DFS gain: The phase 3 POTOMAC trial (NCT03528694, 1,018 patients) showed a 32% risk reduction in disease-free survival (DFS) in the durvalumab plus BCG (induction plus maintenance) arm compared with BCG alone (HR 0.68; 95% CI 0.50-0.93; p=0.0154).
• Expanded analysis: In data presented at AUA 2026, the high-risk event rate in the first year was 16% in the durvalumab arm and 20% in the BCG-alone arm; median time to event was reported as 14.1 months and 8.3 months respectively.
• Reduction in cystectomy: Among patients developing BCG-unresponsive disease, the cystectomy rate was 8% in the durvalumab arm and 25% in the BCG-alone arm.
• Safety: At a median follow-up of 66 months, no detrimental effect on overall survival from the addition of durvalumab was observed (HR 0.80; 95% CI 0.53-1.20).

Background and Study Design

High-risk, BCG-naive non-muscle-invasive bladder cancer (NMIBC) represents a patient group at high risk of recurrence and progression despite intravesical BCG immunotherapy. Development of BCG-unresponsive disease is accepted in current guidelines as an indication for radical cystectomy, which imposes a significant burden of quality-of-life impairment and morbidity on patients. Whether adding the PD-L1 inhibitor durvalumab to BCG could reduce this risk was the core research question of the POTOMAC trial.

POTOMAC is a multicentre, open-label phase 3 trial that randomized 1,018 patients with BCG-naive high-risk NMIBC 1:1:1 to three arms. The first patient was enrolled in June 2018, the last BCG dose was given in January 2023 and the data cut-off was 3 April 2025. The primary analysis was published in The Lancet in 2025; the expanded analyses presented at the AUA 2026 Annual Meeting by Neal D. Shore, MD (START Carolinas/Carolina Urologic Research Center) revealed new data on early recurrence, time to cystectomy, papillary tumour subgroups and immune-related adverse events.

Study Design: POTOMAC

Key Results

In the safety profile, immune-related adverse events (irAEs) added by the durvalumab arm were seen in 27% of patients; the most frequent were hypothyroidism (11%), hepatic events (5%) and dermatitis/rash (3%). The rate of grade 3-4 irAEs was 8%, and no treatment-related fatal events were reported in either arm. Importantly, the addition of durvalumab did not adversely affect patients' capacity to receive adequate BCG therapy (87% versus 93%).

"These data, together with an appropriate shared decision-making process, clearly support one year of durvalumab plus induction-maintenance BCG as a potential new treatment option for patients with BCG high-risk NMIBC." - Neal D. Shore, MD, FACS, START Carolinas/Carolina Urologic Research Center, POTOMAC Co-Principal Investigator

Implications for Clinical Practice

1. Preventing BCG-unresponsive disease and reducing the need for cystectomy

In the management of NMIBC, preventing BCG-unresponsive disease and reducing the proportion of patients proceeding to cystectomy is critically important both for oncological outcomes and for quality of life. The POTOMAC data show that adding immunotherapy to BCG can make a meaningful contribution in both areas; in particular, the lengthening of time to cystectomy and the fall in the cystectomy rate from 25% to 8% among BCG-unresponsive patients provide an important argument in patient counselling.

2. Indirect effect on robotic radical cystectomy practice

For robotic radical cystectomy practice, these findings have an indirect but important effect on patient selection and timing: if an effective immunotherapy combination in high-risk NMIBC increases the chance of preserving the bladder, the population directed to cystectomy may be confined to more advanced, genuinely BCG-unresponsive or progressive disease.

3. Careful assessment of toxicity risk

The risk of irAEs (27%) and the rate of grade 3-4 toxicity (8%) need to be carefully assessed in patient selection and multidisciplinary follow-up.

4. An individualised treatment decision

With the FDA approval of 28 May 2026, durvalumab plus BCG has become an approved treatment option for BCG-naive high-risk NMIBC; however, the decision to start treatment must be individualised within the framework of the patient's risk profile, comorbidities and shared decision-making.

Conclusion

The POTOMAC data underpinning the FDA approval and the expanded analyses presented at AUA 2026 establish durvalumab plus BCG as a treatment option that extends disease-free survival, reduces the need for cystectomy and has no detrimental effect on overall survival in BCG-naive high-risk NMIBC. With more than five years of follow-up, POTOMAC is the most mature immunotherapy-BCG combination dataset in this field and may contribute to a reshaping of NMIBC treatment algorithms in uro-oncology practice.

References

• FDA. FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. 28 May 2026. - fda.gov
• Urology Times. AUA 2026: Expanded POTOMAC analyses support durvalumab plus BCG. 15 May 2026. - urologytimes.com
• OncLive. Durvalumab Plus BCG Reduces High-Risk NMIBC Recurrence or Death Risk by 32% in Phase 3 POTOMAC Trial. - onclive.com
• Targeted Oncology. FDA Approves Durvalumab Plus BCG for High-Risk NMIBC. - targetedonc.com
• AstraZeneca. IMFINZI (durvalumab) regimen reduced early disease recurrence in POTOMAC Phase III trial exploratory analyses. - astrazeneca.com
• De Santis M, Palou Redorta J, Nishiyama H, et al. Durvalumab plus BCG induction and maintenance in BCG-naive, high-risk NMIBC (POTOMAC): a phase 3 trial. Lancet. 2025;406(10516):2221-2234.