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EAU 2026

EAU 2026: State-of-the-Art Lecture: BCG-Naïve NMIBC in 2025: Are We Moving Beyond BCG Alone?

(UroToday.com) The 2026 European Association of Urology (EAU) Annual Meeting held in London, U.K., between March 13th and 16th 2026, was host to the Urothelial Cancer: Towards Integrated Therapeutic Strategies plenary Session. Dr. Evanguelos Xylinas opened this session with a talk titled BCG-Naïve NMIBC in 2025: Are We Moving Beyond BCG Alone?

Dr. Xylinas began by reviewing three major trials evaluating treatment intensification strategies for patients with high-risk NMIBC: CREST, ALBAN, and POTOMAC.1-3 A key distinction among these studies is the duration of BCG maintenance and the immunotherapy agents used. In the CREST and POTOMAC trials, BCG maintenance is administered for two years, combined with systemic immunotherapy, sasanlimab in CREST and durvalumab in POTOMAC, both given for up to one year. In contrast, the ALBAN trial evaluates a shorter, one-year BCG schedule combined with atezolizumab administered every four weeks for one year. The primary endpoints also vary slightly across trials but generally focus on event-free or disease-free survival, incorporating outcomes such as high-grade recurrence, disease progression, carcinoma in situ recurrence, or death.

 

 
The ALBAN trial was negative, showing no improvement in event-free survival with the addition of atezolizumab to BCG compared with BCG alone (HR 0.98; p=0.91). In contrast, both the CREST and POTOMAC trials demonstrated positive results. In CREST, the addition of sasanlimab to BCG significantly improved event-free survival compared with BCG alone (HR 0.68; p=0.0095). Similarly, the POTOMAC trial showed improved disease-free survival with durvalumab plus BCG compared with BCG alone (HR 0.68; p=0.0154).1-3

The ALBAN trial was negative, showing no improvement in event-free survival with the addition of atezolizumab to BCG compared with BCG alone (HR 0.98; p=0.91). In contrast, both the CREST and POTOMAC trials demonstrated positive results. In CREST, the addition of sasanlimab to BCG significantly improved event-free survival compared with BCG alone (HR 0.68; p=0.0095). Similarly, the POTOMAC trial showed improved disease-free survival with durvalumab plus BCG compared with BCG alone (HR 0.68; p=0.0154). (1-3)

When evaluating these trials, the first question is whether the magnitude of benefit is truly meaningful. He noted that the validity of these results should be interpreted in the context of historical outcomes with BCG, which continue to serve as the benchmark in this disease setting. To illustrate this point, he reviewed the NIMBUS trial, which evaluated reduced frequency versus standard frequency BCG instillations.4 The study demonstrated inferior outcomes with the reduced frequency schedule, with a hazard ratio for recurrence of 0.403 (97.5% CI 0.241–0.676), reinforcing the importance of appropriate control arms and confirming that historical BCG data remain a valid comparator when interpreting contemporary trials.

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Dr. Xylinas then discussed the reasons why the ALBAN trial was negative,1 emphasizing that the results should not necessarily be interpreted as a failure of the drug itself. Instead, he highlighted several trial design factors that may have contributed to the negative outcome. These included the use of atezolizumab, truncation of BCG maintenance to one year, and the inclusion of a lower-risk high-risk NMIBC population. Additionally, the event-free survival endpoint incorporated low-grade recurrences, which may have diluted the ability to detect a meaningful treatment effect.

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Third, the clinical relevance of the event-free and disease-free survival benefits reported in recent trials was discussed by Dr. Xylinas. He emphasized that in both the CREST and POTOMAC studies,2,3 the improvement in EFS and DFS was primarily driven by reductions in high-grade disease recurrence. He noted that patients who develop high-grade recurrence after BCG are often on the pathway toward BCG-unresponsive disease, which has important clinical implications. In this context, preventing high-grade recurrence is meaningful, as these patients may ultimately require radical cystectomy if the disease progresses.

Third, the clinical relevance of the event-free and disease-free survival benefits reported in recent trials was discussed by Dr. Xylinas. He emphasized that in both the CREST and POTOMAC studies,2,3 the improvement in EFS and DFS was primarily driven by reductions in high-grade disease recurrence. He noted that patients who develop high-grade recurrence after BCG are often on the pathway toward BCG-unresponsive disease, which has important clinical implications. In this context, preventing high-grade recurrence is meaningful, as these patients may ultimately require radical cystectomy if the disease progresses.

Moreover, Dr. Xylinas highlighted that BCG maintenance remains a critical component of treatment despite attempts at therapeutic intensification. Reviewing data from the CREST and POTOMAC trials, he emphasized that adequate maintenance BCG for two years appears to be essential, suggesting that the addition of immune checkpoint inhibitors may provide limited benefit if maintenance BCG is not properly administered. He underscored that optimal delivery of BCG maintenance should remain a priority when interpreting the results of these combination strategies.

Moreover, Dr. Xylinas highlighted that BCG maintenance remains a critical component of treatment despite attempts at therapeutic intensification. Reviewing data from the CREST and POTOMAC trials, he emphasized that adequate maintenance BCG for two years appears to be essential, suggesting that the addition of immune checkpoint inhibitors may provide limited benefit if maintenance BCG is not properly administered. He underscored that optimal delivery of BCG maintenance should remain a priority when interpreting the results of these combination strategies.

The fifth point addressed overall survival in the context of treatment intensification. Neither the CREST nor the POTOMAC trials demonstrated an improvement in overall survival with the addition of immune checkpoint inhibition. In the NMIBC setting, overall survival is not typically considered the most relevant endpoint. However, these findings are reassuring in that adding an immune checkpoint inhibitor does not appear to negatively impact overall survival.2,3

The fifth point addressed overall survival in the context of treatment intensification. Neither the CREST nor the POTOMAC trials demonstrated an improvement in overall survival with the addition of immune checkpoint inhibition. In the NMIBC setting, overall survival is not typically considered the most relevant endpoint. However, these findings are reassuring in that adding an immune checkpoint inhibitor does not appear to negatively impact overall survival.2,3

In terms of adverse events, treatment intensification was associated with higher rates of toxicity in both the CREST and POTOMAC trials. However, most events were low grade and consistent with the expected safety profiles of BCG and immune checkpoint inhibitors. Urinary symptoms such as dysuria, hematuria, and pollakiuria were among the most commonly reported adverse events, while immune-related events remained relatively infrequent. Overall, the safety profile of these combination strategies appeared manageable.2,3

In terms of adverse events, treatment intensification was associated with higher rates of toxicity in both the CREST and POTOMAC trials. However, most events were low grade and consistent with the expected safety profiles of BCG and immune checkpoint inhibitors. Urinary symptoms such as dysuria, hematuria, and pollakiuria were among the most commonly reported adverse events, while immune-related events remained relatively infrequent. Overall, the safety profile of these combination strategies appeared manageable.2,3

More specifically, immune-related toxicity in the CREST trial did not appear to increase substantially with the addition of BCG. The incidence and severity of immune-related adverse events were comparable between treatment groups. Most events were low grade, with thyroid disorders and rash among the most commonly reported immune-related toxicities, while higher-grade immune-related events remained relatively uncommon.2

More specifically, immune-related toxicity in the CREST trial did not appear to increase substantially with the addition of BCG. The incidence and severity of immune-related adverse events were comparable between treatment groups. Most events were low grade, with thyroid disorders and rash among the most commonly reported immune-related toxicities, while higher-grade immune-related events remained relatively uncommon.2

These adverse event rates appear acceptable and are comparable to those observed with immune checkpoint inhibitors in the BCG unresponsive setting. Data from studies such as KEYNOTE 057, SWOG S1605, and SUNRISE 1 demonstrate similar toxicity profiles, with grade 3 to 4 immune-related adverse events occurring in approximately 8 to 14 percent of patients and serious adverse events reported in roughly 4 to 9 percent, as shown below.

These adverse event rates appear acceptable and are comparable to those observed with immune checkpoint inhibitors in the BCG unresponsive setting. Data from studies such as KEYNOTE 057, SWOG S1605, and SUNRISE 1 demonstrate similar toxicity profiles, with grade 3 to 4 immune-related adverse events occurring in approximately 8 to 14 percent of patients and serious adverse events reported in roughly 4 to 9 percent, as shown below.

The next important question is identifying which patients may be the best candidates for these intensified treatment strategies. Subgroup analyses from the CREST trial suggest that the event-free survival benefit was generally consistent across multiple patient groups, including those with CIS and T1 disease. These findings indicate that the benefit of treatment intensification may extend broadly across high-risk NMIBC populations, although further work is needed to better refine patient selection.

The next important question is identifying which patients may be the best candidates for these intensified treatment strategies. Subgroup analyses from the CREST trial suggest that the event-free survival benefit was generally consistent across multiple patient groups, including those with CIS and T1 disease. These findings indicate that the benefit of treatment intensification may extend broadly across high-risk NMIBC populations, although further work is needed to better refine patient selection.

In this population, early radical cystectomy is often considered the preferred management strategy rather than intravesical BCG. However, an exploratory analysis in patients with very high-risk disease showed a potential event-free survival benefit with treatment intensification using sasanlimab plus BCG compared with BCG alone in this subgroup, although these findings should be interpreted cautiously given the limited sample size.

In this population, early radical cystectomy is often considered the preferred management strategy rather than intravesical BCG. However, an exploratory analysis in patients with very high-risk disease showed a potential event-free survival benefit with treatment intensification using sasanlimab plus BCG compared with BCG alone in this subgroup, although these findings should be interpreted cautiously given the limited sample size.

Dr. Xylinas concluded with several key take-home points:

  • The available randomized clinical trials are well designed, fully accrued, and now include meaningful follow-up.
  • Treatment intensification strategies in high-risk NMIBC appear to provide a benefit in event-free and disease-free survival, primarily driven by reductions in high-grade disease recurrence.
  • These benefits must be balanced with the expected immune-related toxicity associated with checkpoint inhibition.
  • Careful patient selection remains essential, particularly in identifying those most likely to benefit, including patients with very high-risk disease and those defined by emerging biomarker profiles.

Presented by: Evanguelos Xylinas, MD, PhD, FEBU, Professor of Urology, Head of Urologic Oncology Unit, Paris University, APHP Nord Bichat-Claude Bernard Hospital, Paris, France

Written by: Julian Chavarriaga, MD, Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health. @chavarriagaj on X during the 2026 European Association of Urology (EAU) Annual Meeting, London, United Kingdom, Fri, Mar 13 – Mon, Mar 16, 2026. 

References:

 

  1. Roupret M, Bertaut A, Pignot G, Neuzillet Y, Houede N, Mathieu R, Corbel L, Besson D, Seisen T, Jaffrelot L, Lebacle C, Champiat S, Lebdai S, Timsit MO, Thibault C, Goeman L, Juárez Soto Á, La C, Léger C, Loriot Y. ALBAN (GETUG-AFU 37): a phase III, randomized, open-label international trial of intravenous atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) versus BCG alone in BCG-naive high-risk, non-muscle-invasive bladder cancer (NMIBC). Ann Oncol. 2026 Jan;37(1):44-52. doi: 10.1016/j.annonc.2025.09.017. Epub 2025 Oct 17. PMID: 41110692.
  2. Steinberg GD, Shore ND, Redorta JP, Galsky MD, Bedke J, Ku JH, Kretkowski M, Hu H, Penkov K, Vermette JJ, Tarazi JC, Randall AE, Pierce KJ, Saltzstein D, Powles TB. CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer. Future Oncol. 2024 May;20(14):891-901. doi: 10.2217/fon-2023-0271. Epub 2024 Jan 8. PMID: 38189180.
  3. De Santis M, Palou Redorta J, Nishiyama H, Krawczyński M, Seyitkuliev A, Novikov A, Guerrero-Ramos F, Zukov R, Kato M, Kawahara T, Goeman L, Puente J, Hellmis E, Powles T, Radziszewski P, Gust KM, Vasey P, Bigot P, Fradet Y, Hunting J, Armstrong J, Boulos S, Hois S, Shore ND; POTOMAC Investigators. 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 Nov 8;406(10516):2221-2234. doi: 10.1016/S0140-6736(25)01897-5. Epub 2025 Oct 17. PMID: 41115436.
  4. Grimm MO, van der Heijden AG, Colombel M, Muilwijk T, Martínez-Piñeiro L, Babjuk MM, Türkeri LN, Palou J, Patel A, Bjartell AS, Caris C, Schipper RG, Witjes WPJ; EAU Research Foundation NIMBUS Study Group. 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 Nov;78(5):690-698. doi: 10.1016/j.eururo.2020.04.066. Epub 2020 May 20. PMID: 32446864.