BCG Optimization Becomes a Priority as Durvalumab Gains a Role in High-Risk NMIBC

Adding durvalumab (Imfinzi) to BCG is a Level 1 evidence–supported treatment option for first-line high-risk non–muscle-invasive bladder cancer (NMIBC), but optimizing BCG delivery remains the most important step to take, and biomarkers, such as circulating tumor DNA (ctDNA), will likely determine who benefits from treatment intensification, according to Tom Jayram, MD.¹

In a presentation at the 2026 LUGPA Annual Meeting, Jayram outlined how to strengthen BCG practices; reviewed efficacy, safety, and quality-of-life data from the phase 3 POTOMAC trial (NCT03528694); and discussed the emerging role of ctDNA in NMIBC.

Jayram is co-director of the Advanced Therapeutics Center at Urology Associates, P.C., in Nashville, Tennessee.

Why should BCG delivery be optimized before systemic therapy is considered in NMIBC?

The National Comprehensive Cancer Network Guidelines list BCG induction followed by maintenance as the preferred approach for patients with BCG-naive, high-risk NMIBC.² Jayram said he believes “a lot of [patient progression on] BCG [is] not because the disease is really bad, but because we’re doing a poor job of getting our patients on BCG.”¹

He cited findings from the phase 3 NIMBUS trial, in which 345 patients were randomly assigned to a reduced-frequency BCG schedule (n = 170) or a standard-frequency BCG schedule (n = 175), with re-resection required.³ The respective recurrence rates were higher with reduced-frequency vs standard dosing at 6, 12, and 24 months. Jayram argued the reduced-frequency population resembles that most commonly found in real-world community practice, where patients often complete only some instillations.¹ To improve first-line outcomes, he recommended a thorough resection with a restaging resection for high-grade disease, standardized pathology reporting, blue-light or narrow-band imaging, and strict induction and maintenance, with longer maintenance shown to help.

What does POTOMAC show about adding durvalumab to BCG in NMIBC?

POTOMAC was an open-label phase 3 study that enrolled 1018 patients with high-risk NMIBC who had not previously received BCG. Patients were randomly assigned 1:1:1 to receive durvalumab plus BCG induction and maintenance (n = 339), durvalumab plus BCG induction alone (n = 339), or BCG induction and maintenance alone (n = 340).⁴ With a median follow-up of 60.7 months, durvalumab plus BCG induction and maintenance improved disease-free survival (DFS) vs BCG alone, lowering the risk of high-risk recurrence or death (HR, 0.68; 95% CI, 0.50-0.93; P = .0154), respectively. Based on these data, the FDA approved durvalumab with BCG for this patient population on May 28, 2026.⁵

Jayram noted that despite these findings, the BCG-alone comparator arm performed well.¹ “It is hard to beat BCG in this setting,” he said. Most of patients had high-grade T1 disease, which he suggested makes each recurrence more consequential.

New POTOMAC analyses from the 2026 American Urological Association Annual Meeting added support.⁶ The median time to events was 14.1 months with durvalumab plus BCG induction and maintenance vs 8.3 months with BCG alone, respectively. Cystectomy rates favored the durvalumab arm (HR, 0.63; 95% CI, 0.31-1.24), as did cystectomy-free survival outcomes (HR, 0.69; 95% CI, 0.48-0.99).

“Cystectomy-free survival is probably the most meaningful end point to our patients in this setting,” Jayram said.¹ He added that “[durvalumab] is probably a meaningful treatment for younger patients who are motivated and can tolerate the therapy.”

How should safety and quality of life shape patient selection for NMIBC therapy?

Adding durvalumab had no major effect on patient-reported global health status on the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire in POTOMAC, and Jayram noted a similar pattern with sasanlimab plus BCG in the phase 3 CREST trial.¹

Jayram emphasized the importance of explaining to patients the approximately 5%-to-10% risk of needing to receive thyroid hormone replacement therapy for the rest of their lives. He urged the bladder cancer community to find clearer ways to communicate these risks to patients.

What may be the future role of biomarkers in high-risk NMIBC?

Jayram called ctDNA “a profound marker for bladder cancer.” In a single-institution retrospective analysis of 23 patients with NMIBC from Cleveland Clinic, ctDNA was detected in 35%.⁷ Some patients tested positive despite no cystoscopic or radiographic findings. “[That is] the perfect population to intensify with checkpoint inhibitors plus BCG,” he said.¹

He encouraged use of the Natera-sponsored SCORE-NMIBC study (NCT07763197) registry, which is prospectively tracking how often ctDNA positivity occurs in high-risk NMIBC.⁸ Overall, Jayram said that “first shot, best shot” is a reasonable approach for managing aggressive disease, though overall survival data are still needed.¹

References

1. Jayram T. Systemic therapy in BCG-naive NMIBC: is it worth it? Presented at: LUGPA 18th Annual Meeting; November 5-7, 2026; Chicago, IL.
2. NCCN. Clinical Practice Guidelines in Oncology. Bladder cancer, version 3.2026. August 6, 2026. Accessed November 5, 2026. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
3. Grimm MO, van der Heijden AG, Colombel M, et al. Treatment of high-grade non-muscle-invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations: results of the European Association of Urology Research Foundation randomised phase III clinical trial “NIMBUS”. Eur Urol. 2020;78(5):690-698. doi:10.1016/j.eururo.2020.04.066
4. De Santis M, Palou Redorta J, Nishiyama H, et al. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025;406(10516):2221-2234. doi:10.1016/S0140-6736(25)01897-5
5. FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. FDA. May 28, 2026. Accessed November 5, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-combination-bacillus-calmette-guerin-high-risk-non-muscle-invasive-bladder
6. Shore ND, De Santis M, Redorta JP, et al. Durvalumab in combination with bacillus Calmette-Guérin induction and maintenance in BCG-naive, non-muscle-invasive bladder cancer: expanded efficacy and safety analyses from POTOMAC. Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC.
7. Wang B, Davis LE, Weight CJ, Abouassaly R, Bukavina L. Real-world experience with a commercial circulating tumor DNA assay in non-muscle-invasive bladder cancer. Eur Urol Oncol. 2025;8(4):883-887. doi:10.1016/j.euo.2025.05.019
8. Sample collection for ongoing research and product evaluation study - non-muscle invasive bladder cancer (SCORE-NMIBC) (SCORE-NMIBC). ClinicalTrials.gov. Updated August 13, 2026. Accessed November 5, 2026. https://clinicaltrials.gov/study/NCT07763197