The ESMO Congress 2026 will feature several important updates across urothelial cancer, with a major focus on perioperative treatment for muscle-invasive bladder cancer (MIBC). Phase III studies will evaluate checkpoint inhibition alongside cisplatin-based chemotherapy, while additional analyses will explore circulating tumor DNA (ctDNA), molecular subtypes, health-related quality of life, and outcomes in specific patient populations.
Other presentations will address high-risk non-muscle-invasive bladder cancer (NMIBC), metastatic urothelial cancer, and upper tract urothelial carcinoma (UTUC). This overview highlights 10 bladder and urothelial cancer studies to watch at ESMO 2026.
KEYNOTE-866: Perioperative Pembrolizumab Plus Cisplatin and Gemcitabine in MIBC
Abstract: 4735O
Presenter: Jens Bedke (Stuttgart, Germany)
Trial Type: Phase III
Session: Proffered Paper session
KEYNOTE-866 (NCT03924856) is a randomized phase III trial evaluating perioperative pembrolizumab versus placebo in combination with neoadjuvant gemcitabine and cisplatin in patients with cisplatin-eligible MIBC. Patients receive four cycles of neoadjuvant treatment followed by radical cystectomy and pelvic lymph-node dissection, with pembrolizumab or placebo continued postoperatively.
The primary endpoint is event-free survival; secondary endpoints include pathological complete response, overall survival, disease-free survival, and pathological downstaging.
At ESMO 2026, KEYNOTE-866 will report the phase III comparison of perioperative pembrolizumab versus placebo, each combined with neoadjuvant cisplatin-gemcitabine, in cisplatin-eligible MIBC.
ENERGIZE: Neoadjuvant Chemotherapy With or Without Nivolumab in MIBC
Abstract: 4736O
Presenter: Andrea Necchi (Milan, Italy)
Trial Type: Phase III
Session: Proffered Paper session
ENERGIZE (NCT03661320) is a phase III study in patients with cisplatin-eligible MIBC. The original study design evaluated neoadjuvant gemcitabine-cisplatin alone, gemcitabine-cisplatin plus nivolumab followed by postoperative nivolumab, and gemcitabine-cisplatin plus nivolumab and linrodostat followed by postoperative nivolumab and linrodostat.
At ESMO 2026, ENERGIZE will report results comparing neoadjuvant chemotherapy alone with neoadjuvant chemotherapy plus nivolumab followed by postoperative nivolumab.
KEYNOTE-905: Perioperative Pembrolizumab or EV Plus Pembrolizumab in Cisplatin-Ineligible MIBC
Abstract: 4733O
Presenter: Anders Ullén (Stockholm, Sweden)
Trial Type: Phase III, ad hoc analysis
Session: Proffered Paper session
KEYNOTE-905/EV-303 (NCT03924895) is a randomized phase III program evaluating perioperative pembrolizumab alone, perioperative enfortumab vedotin (EV) plus pembrolizumab, and surgery alone in patients with MIBC who were ineligible for or declined cisplatin-based chemotherapy.
The EV plus pembrolizumab comparison was published in The New England Journal of Medicine in 2026. At 2 years, event-free survival was 74.7% with EV plus pembrolizumab versus 39.4% with surgery alone, while overall survival was 79.7% versus 63.1%. Pathological complete response occurred in 57.1% versus 8.6% of patients.
At ASCO 2026, a prespecified exploratory HRQoL analysis showed no clinically meaningful deterioration in general or cystectomy-specific health-related quality of life at 18 weeks after surgery; no formal between-group comparison was performed. On November 21, 2025, the FDA initially approved perioperative pembrolizumab plus EV for adults with MIBC who are ineligible for cisplatin.
At ESMO 2026, an ad hoc analysis will report outcomes involving the perioperative pembrolizumab and EV plus pembrolizumab treatment strategies.
KEYNOTE-B15: ctDNA Analysis of Perioperative EV Plus Pembrolizumab
Abstract: 4734O
Presenter: Jonathan A. Chatzkel (Tampa, United States)
Trial Type: Phase III, ctDNA analysis
Session: Proffered Paper session
KEYNOTE-B15/EV-304 (NCT04700124) compared perioperative EV plus pembrolizumab with neoadjuvant gemcitabine-cisplatin followed by surgery in patients with cisplatin-eligible MIBC.
The primary results were published on July 22, 2026, in The New England Journal of Medicine. At 2 years, event-free survival was 79.4% with EV plus pembrolizumab versus 66.2% with gemcitabine-cisplatin, while overall survival was 86.9% versus 81.3%. Pathological complete response occurred in 55.8% versus 32.5% of patients.
At ESMO 2026, investigators will present a ctDNA analysis from KEYNOTE-B15.
KEYNOTE-B15: Health-Related Quality of Life With EV Plus Pembrolizumab
Abstract: 4738RO
Presenter: Alfonso Gomez de Liano Lista (Las Palmas de Gran Canaria, Spain)
Trial Type: Phase III, HRQoL analysis
Session: Rapid Oral session
A second KEYNOTE-B15 presentation will focus on health-related quality of life with neoadjuvant and adjuvant EV plus pembrolizumab in cisplatin-eligible patients with MIBC. The analysis follows the phase III results showing improved event-free survival, overall survival, and pathological complete response with perioperative EV plus pembrolizumab compared with neoadjuvant gemcitabine-cisplatin.
At ESMO 2026, KEYNOTE-B15 will report health-related quality-of-life outcomes with perioperative EV plus pembrolizumab.
NIAGARA: Molecular Subtypes and Treatment Outcomes in MIBC
Abstract: 4741RO
Presenter: Matthew D. Galsky (New York, United States)
Trial Type: Phase III, exploratory molecular analysis
Session: Rapid Oral session
NIAGARA (NCT03732677) evaluated perioperative durvalumab plus neoadjuvant gemcitabine-cisplatin versus neoadjuvant gemcitabine-cisplatin alone in patients with cisplatin-eligible MIBC. The primary analysis was published in The New England Journal of Medicine in 2024. Estimated 24-month event-free survival was 67.8% with the durvalumab-containing strategy versus 59.8% with the comparator, while 24-month overall survival was 82.2% versus 75.2%, respectively.
At ESMO 2026, NIAGARA will report an exploratory analysis of molecular subtypes and their association with treatment outcomes.
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GDFather-NEO: Nivolumab With or Without Visugromab in MIBC
Abstract: 4757RO
Presenter: Andrea Necchi (Milan, Italy)
Trial Type: Phase II
Session: Rapid Oral session
GDFather-NEO (NCT06059547) is a blinded exploratory phase II trial evaluating neoadjuvant nivolumab with either visugromab, a GDF-15-neutralizing antibody, or placebo in patients with MIBC. Initial results presented at ESMO 2025 showed higher pathological complete response, major pathological response, and radiological response rates with nivolumab plus visugromab than with nivolumab plus placebo.
At ESMO 2026, GDFather-NEO will report final pathological and radiological outcomes together with initial event-free survival data.
POTOMAC: Durvalumab Plus BCG in Papillary-Only High-Risk NMIBC
Abstract: 4737RO
Presenter: Maria De Santis (Berlin, Germany)
Trial Type: Phase III, subgroup analysis
Session: Rapid Oral session
POTOMAC (NCT03528694) is a randomized phase III trial evaluating durvalumab in combination with BCG in patients with BCG-naïve, high-risk NMIBC. The final analysis, published in The Lancet in 2025, showed that durvalumab plus BCG induction and maintenance reduced the risk of high-risk disease recurrence or death compared with BCG induction and maintenance alone (HR 0.68; 95% CI 0.50–0.93; P=0.015). On May 28, 2026, the FDA approved durvalumab plus BCG for adults with BCG-naïve, high-risk NMIBC.
At ASCO 2026, the 5-year overall survival rate was 87.6% with durvalumab plus BCG versus 86.3% with BCG alone (HR 0.81; 95% CI 0.54–1.19), while patient-reported outcomes were generally similar between groups.
At ESMO 2026, POTOMAC will report early recurrence and cystectomy-free survival in patients with papillary-only tumors.
TROPHY-U-01 Cohort 7: SG Plus EV and Zimberelimab in Treatment-Naïve mUC
Abstract: 4742O
Presenter: Randy Sweis (Chicago, United States)
Trial Type: Phase Ib, interim analysis
Session: Proffered Paper session
TROPHY-U-01 (NCT03547973) is a multicohort study evaluating sacituzumab govitecan alone and in combination with other agents in advanced urothelial cancer. The phase Ib portion of Cohort 7 evaluates sacituzumab govitecan combined with enfortumab vedotin and the PD-1 inhibitor zimberelimab in treatment-naïve metastatic urothelial cancer.
At ESMO 2026, Cohort 7 will report interim phase Ib results of sacituzumab govitecan plus enfortumab vedotin and zimberelimab.
WUTSUP-02: Neoadjuvant Tislelizumab Plus Disitamab Vedotin in UTUC
Abstract: 4749RO
Trial Type: Phase II
Session: Rapid Oral session
WUTSUP-02 (ChiCTR2300067836) is a multicenter phase II study evaluating neoadjuvant tislelizumab plus disitamab vedotin followed by adjuvant tislelizumab in patients with high-risk upper tract urothelial carcinoma. It includes four cycles of neoadjuvant tislelizumab plus disitamab vedotin before radical nephroureterectomy, followed by eight cycles of postoperative tislelizumab. The primary endpoint is pathological complete response.
At ESMO 2026, WUTSUP-02 will present mid-term results of this perioperative strategy in high-risk UTUC.
The Bottom Line
The ESMO 2026 urothelial cancer program places perioperative MIBC at the center of attention, with phase III results and secondary analyses across KEYNOTE-866, ENERGIZE, KEYNOTE-905, KEYNOTE-B15, and NIAGARA.
Beyond the primary efficacy readouts, ctDNA, molecular subtype, and health-related quality-of-life analyses will provide additional data from major perioperative trials. GDFather-NEO will report further results with GDF-15 blockade, POTOMAC will examine papillary-only high-risk NMIBC, TROPHY-U-01 Cohort 7 will provide interim data from a dual-ADC plus immunotherapy combination, and WUTSUP-02 will present data specifically in high-risk UTUC.
Together, these studies will provide new data across muscle-invasive, non-muscle-invasive, metastatic, and upper tract urothelial cancer settings.
Full abstract details are available in the official ESMO programme.
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