ESMO 2026 bladder cancer round-up: Five key abstracts not to miss

New data from VOLGA, KEYNOTE-B15, ENERGIZE, KEYNOTE-866 and POTOMAC examine perioperative treatment combinations, circulating tumor DNA (ctDNA) and bladder-preserving strategies across muscle-invasive and non-muscle-invasive bladder cancer.

How might new treatment combinations and emerging biomarkers inform bladder cancer management? Five studies selected from the European Society for Medical Oncology (ESMO) Congress 2026 address this question across different disease settings: VOLGA, KEYNOTE-B15/EV-304, ENERGIZE, KEYNOTE-866 and POTOMAC. Their findings examine perioperative treatment intensification, the potential of circulating tumor DNA (ctDNA) to characterize treatment response and the addition of immunotherapy to bacillus Calmette–Guérin (BCG) in high-risk non-muscle-invasive disease.

VOLGA: Perioperative durvalumab plus enfortumab vedotin in cisplatin-ineligible MIBC

Abstract: LBA2 | ClinicalTrials.gov: NCT04960709 | Phase: III

VOLGA evaluated perioperative durvalumab, with or without tremelimumab, plus neoadjuvant enfortumab vedotin (EV) in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or refused cisplatin. The trial randomized 695 patients to durvalumab plus EV, durvalumab plus tremelimumab and EV, or control treatment comprising radical cystectomy and observation or locally approved adjuvant treatment. At a median event-free survival (EFS) follow-up of 22.9 months, durvalumab plus EV significantly improved EFS compared with control (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.38–0.67; P<0.0001), with 24-month rates of 64% versus 45%. Overall survival (OS) also improved significantly (HR, 0.58; 95% CI, 0.40–0.83; P=0.0027), with 24-month rates of 78% versus 69%. Adding tremelimumab also significantly improved EFS but did not meet the significance threshold for OS. Grade 3/4 treatment-related adverse events occurred in 30% of patients receiving durvalumab plus EV and 42% receiving the tremelimumab-containing regimen.

Key clinical takeaway: Perioperative durvalumab plus neoadjuvant EV improved EFS and OS compared with radical cystectomy and observation or locally approved adjuvant treatment. The higher incidence of grade 3/4 treatment-related adverse events with the tremelimumab-containing regimen is an important consideration when interpreting the results. Longer follow-up is ongoing.

KEYNOTE-B15/EV-304: ctDNA analysis of perioperative enfortumab vedotin plus pembrolizumab

Abstract: 4734O | ClinicalTrials.gov: NCT04700124 | Phase: III

This exploratory analysis of KEYNOTE-B15/EV-304 evaluated circulating tumor DNA (ctDNA) status and clearance in patients with MIBC who were eligible for cisplatin and received perioperative EV plus pembrolizumab or neoadjuvant cisplatin and gemcitabine. Among 808 randomized patients, ctDNA clearance was higher with EV plus pembrolizumab than with chemotherapy (82.1% vs 66.7%). ctDNA-negative status before neoadjuvant treatment or after surgery was associated with improved EFS and pathological complete response (pCR) in both arms. EV plus pembrolizumab showed an EFS benefit over chemotherapy regardless of ctDNA status at either time point. Patients with ctDNA clearance also had more favorable EFS and pCR outcomes than those without clearance.

Key clinical takeaway: In this exploratory analysis, ctDNA positivity was associated with poorer prognosis, while ctDNA clearance was associated with more favorable outcomes. These findings support further investigation of ctDNA as a biomarker during perioperative treatment, but they do not establish its utility for guiding treatment decisions. The results should not yet be interpreted as supporting ctDNA-guided treatment selection or modification.

ENERGIZE: Perioperative nivolumab plus chemotherapy in resectable MIBC

Abstract: 4736O | ClinicalTrials.gov: NCT03661320 | Phase: III

ENERGIZE (CA017-078) evaluated neoadjuvant nivolumab plus gemcitabine and cisplatin (GC), followed by surgery and adjuvant nivolumab, compared with neoadjuvant GC followed by surgery alone. The trial randomized 653 patients, with a median follow-up of 54.5 months. EFS did not differ significantly between the groups (HR, 0.94; 95.74% CI, 0.71–1.25; P=0.67). The pCR rate was 39.1% with nivolumab plus GC followed by nivolumab and 29.6% with GC alone (odds ratio, 1.54; 99.91% CI, 0.88–2.69). OS was immature at the EFS final analysis. Grade ≥3 treatment-related adverse events were reported in 45.9% and 49.5% of patients, respectively.

Key clinical takeaway: Perioperative nivolumab plus GC did not significantly improve the primary endpoints of EFS or pCR compared with GC alone. The results highlight the need to assess individual perioperative immunotherapy strategies against their trial-specific efficacy and safety outcomes.

KEYNOTE-866: Perioperative pembrolizumab plus neoadjuvant chemotherapy

Abstract: 4735O | ClinicalTrials.gov: NCT03924856 | Phase: III

KEYNOTE-866 evaluated perioperative pembrolizumab or placebo added to neoadjuvant cisplatin and gemcitabine, followed by radical cystectomy and pelvic lymph node dissection, in cisplatin-eligible patients with MIBC. Among 907 randomized patients, the median follow-up was 60.9 months. Median EFS was 74.1 months with pembrolizumab and was not reached with placebo (HR, 0.88; 95% CI, 0.71–1.10; P=0.1366). The pCR rates were 44.4% and 35.8%, respectively, with an estimated difference of 8.9% (95% CI, 2.5–15.1). Median OS was not reached in either group (HR, 1.00; 95% CI, 0.79–1.27).

Key clinical takeaway: The addition of perioperative pembrolizumab did not confer a statistically significant EFS benefit. Although the pCR rate was numerically higher with pembrolizumab, the study’s statistical design meant that pCR and OS were not formally tested.

POTOMAC: Durvalumab plus BCG in high-risk NMIBC with papillary-only tumors

Abstract: 4737RO | ClinicalTrials.gov: NCT03528694 | Phase: III

This post hoc, exploratory analysis of POTOMAC evaluated durvalumab plus bacillus Calmette–Guérin (BCG) induction and maintenance compared with BCG induction and maintenance alone in patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC) and papillary-only tumors. The overall POTOMAC trial demonstrated a statistically significant disease-free survival (DFS) benefit with durvalumab plus BCG induction and maintenance; however, the supplied abstract does not report a specific DFS estimate for this subgroup. In the exploratory analysis, fewer high-risk disease events occurred with durvalumab plus BCG (28/217) than with BCG alone (44/220). Among patients experiencing recurrence, BCG-unresponsive disease occurred in 11/18 (61%) patients receiving durvalumab plus BCG and 30/34 (88%) receiving BCG alone. Cystectomy-free survival favored durvalumab plus BCG (HR, 0.59; 95% CI, 0.38–0.92), while time to cystectomy showed a numerical difference that was not statistically conclusive (HR, 0.51; 95% CI, 0.18–1.32). Grade 3/4 treatment-related adverse events occurred in 23% and 3% of patients, respectively.

Key clinical takeaway: This post hoc subgroup analysis found fewer high-risk disease events and BCG-unresponsive recurrences with durvalumab plus BCG. Although cystectomy-free survival favored the combination, the time-to-cystectomy estimate was imprecise, with a confidence interval crossing 1. These exploratory findings should be interpreted cautiously and do not establish a definitive benefit for cystectomy-related outcomes in this subgroup. The higher incidence of grade 3/4 treatment-related adverse events with durvalumab plus BCG should also be considered.

This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (Claude.AI and ChatGPT 5.5). The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: ESMO 2026 bladder cancer round-up: Five key abstracts not to miss. touchONCOLOGY. 30th October 2026.

Editor: Sophie Nickelson