ESMO 2026 brought several notable developments in GU Oncology, with clinical trial findings spanning treatment before surgery, intensification strategies, and long-term outcomes in advanced disease. Held in Madrid from October 23–27, the congress presented new randomized evidence alongside mature survival analyses in bladder cancer, prostate cancer, and renal cell carcinoma. From significant improvements in key efficacy endpoints to longer follow-up of established therapies, the findings offered new perspectives on treatment decisions across different clinical settings.
Bladder Cancer: Perioperative Treatment Intensification
In bladder cancer, the ESMO 2026 presentations included Phase III evidence evaluating perioperative combinations in patients with muscle-invasive disease who were ineligible for or declined cisplatin-based chemotherapy.
VOLGA: Durvalumab Plus Enfortumab Vedotin Improves EFS and OS
The Phase III VOLGA trial (LBA2), presented by Thomas Powles and simultaneously published in The New England Journal of Medicine on October 24, 2026, evaluated perioperative durvalumab with or without tremelimumab, combined with neoadjuvant enfortumab vedotin (EV), in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or declined cisplatin-based chemotherapy.
The study randomized 695 patients to durvalumab plus EV (n=233), durvalumab plus tremelimumab and EV (n=233), or radical cystectomy with or without approved adjuvant treatment (n=229). The dual primary endpoints were event-free survival (EFS) for each experimental regimen compared with control, with overall survival (OS) as a key secondary endpoint.
Perioperative durvalumab plus EV significantly improved EFS compared with control (HR 0.51; 95% CI 0.38–0.67; p<0.0001). At 24 months, estimated EFS rates were 63.5% versus 45.1%, respectively. The combination also demonstrated a statistically significant OS benefit (HR 0.58; 95% CI 0.40–0.83; p=0.0027), with 24-month OS rates of 78.4% versus 69.4%.
The tremelimumab-containing regimen also improved EFS compared with control (HR 0.61; 95% CI 0.47–0.80), but did not demonstrate a statistically significant OS benefit at the interim analysis. Grade ≥3 adverse events of any cause occurred in 71.1% of patients receiving durvalumab plus EV, 79.5% receiving the tremelimumab-containing combination, and 50.2% in the control group.
VOLGA demonstrated significant EFS and OS improvements with perioperative durvalumab plus EV in the studied cisplatin-ineligible or cisplatin-declining population. These results provide Phase III evidence for an additional perioperative treatment approach, while the increased incidence of severe adverse events remains relevant to clinical decision-making.
Prostate Cancer: Treatment Intensification and Mature Survival Evidence
In prostate cancer, ESMO 2026 included positive randomized findings in high-risk localized disease and longer-term survival results in de novo metastatic castration-sensitive prostate cancer.
DASL-HiCaP: Darolutamide Improves Metastasis-Free Survival
The Phase III DASL-HiCaP trial (LBA4), presented by Tamim Niazi, evaluated darolutamide versus placebo in combination with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiotherapy.
The study randomized 1,106 patients with very high-risk localized prostate cancer or biochemically persistent or recurrent disease within one year after radical prostatectomy. The primary endpoint was metastasis-free survival assessed by conventional imaging (MFS-CI).
At a median follow-up of 3.8 years, darolutamide significantly improved MFS-CI compared with placebo (HR 0.42; 95% CI 0.27–0.66; p=0.0001), meeting the prespecified interim significance criterion. Four-year MFS rates were 95% with darolutamide versus 88% with placebo. MFS events occurred in 27 versus 63 patients, respectively.
The OS analysis did not demonstrate a statistically significant difference between the treatment groups (HR 0.88; 95% CI 0.49–1.59). Grade ≥3 adverse events of any cause occurred in 43% of patients receiving darolutamide versus 36% receiving placebo. DASL-HiCaP provides positive Phase III evidence for adding darolutamide to ADT and radiotherapy in the studied high-risk population. The MFS benefit was statistically significant, while longer follow-up is required to determine whether this translates into an OS benefit.
PROTEUS Substudy: Perioperative Apalutamide Improves EFS Compared With Surgery Alone
At ESMO 2026, Alberto Briganti presented results from a prespecified randomized substudy of the Phase III PROTEUS trial (LBA53), simultaneously published in European Urology.
The substudy compared perioperative apalutamide plus ADT and radical prostatectomy with immediate radical prostatectomy alone in 408 patients with high-risk localized or locally advanced prostate cancer. A total of 102 patients were assigned to perioperative apalutamide plus ADT and 306 to surgery alone.
At a median follow-up of 37.8 months, the substudy met its primary endpoint of EFS. Median EFS was not reached with apalutamide plus ADT, compared with 19.1 months with surgery alone (HR 0.38; 95% CI 0.26–0.55; p<0.0001). At three years, estimated EFS rates were 63.0% versus 41.4%, respectively.
Metastasis-free survival assessed using conventional or PSMA PET imaging also favored perioperative apalutamide plus ADT (HR 0.49; 95% CI 0.26–0.90; nominal p=0.019). However, the conventional-imaging MFS analysis alone did not demonstrate a statistically significant difference (HR 0.74; p=0.50).
Grade 3–4 treatment-emergent adverse events occurred in approximately 31% of patients receiving perioperative apalutamide plus ADT versus 22% undergoing surgery alone. The PROTEUS substudy demonstrated a statistically significant EFS improvement with perioperative apalutamide plus ADT compared with radical prostatectomy alone. These findings add randomized evidence for treatment intensification in selected high-risk patients, although mature OS outcomes remain unavailable.
PEACE-1: Long-Term Overall Survival With Abiraterone-Based Treatment
Long-term findings from the Phase III PEACE-1 trial (2215O), presented by Karim Fizazi, evaluated the survival impact of adding abiraterone acetate plus prednisone to standard-of-care treatment in de novo metastatic castration-sensitive prostate cancer (mCSPC).
The randomized study included 1,173 patients and used a 2×2 factorial design evaluating abiraterone and prostate radiotherapy in addition to standard-of-care treatment, which consisted of ADT with or without docetaxel.
After a median follow-up of 7.7 years, the addition of abiraterone was associated with a statistically significant OS benefit (HR 0.75; 95% CI 0.65–0.87; p=0.0001). Among 710 patients receiving ADT plus docetaxel as standard of care, median OS was 6.2 years with the addition of abiraterone versus 4.4 years without abiraterone (HR 0.68; 95% CI 0.56–0.82).
Eight-year OS rates were 40.3% with triplet therapy versus 27.1% with ADT plus docetaxel. The updated findings provide longer-term confirmation of the survival benefit associated with abiraterone-containing treatment, including triplet therapy in patients receiving ADT plus docetaxel. The ESMO analysis reinforces an established treatment benefit rather than reporting its first demonstration.
Renal Cell Carcinoma: Significant Efficacy Findings and Long-Term Outcomes
The ESMO 2026 RCC presentations included randomized results in oligometastatic disease, final survival analyses of adjuvant immunotherapy, and updated efficacy findings with targeted treatment combinations in previously treated advanced disease.
PE-PE: Pembrolizumab Plus Metastasis-Directed Therapy Improves RFS
The randomized Phase II PE-PE trial (LBA88), presented by Roberto Iacovelli, evaluated perioperative pembrolizumab plus metastasis-directed therapy (MDT) versus MDT alone in patients with oligometastatic renal cell carcinoma (RCC). The study randomized 85 patients who had previously undergone nephrectomy and were eligible for definitive treatment of metastatic lesions with surgery or stereotactic ablative radiotherapy (SABR). Patients were assigned to pembrolizumab plus MDT (n=56) or MDT alone (n=29). The primary endpoint was relapse-free survival (RFS).
At a median follow-up of 17.5 months, median RFS was 25.4 months with pembrolizumab plus MDT versus 11.0 months with MDT alone (HR 0.47; 95% CI 0.24–0.92; p=0.024). The presented RFS analysis included 54 and 29 patients, respectively. Grade 3 adverse events occurred in 7% versus 3% of patients, respectively. Overall survival data remained immature.
PE-PE demonstrated a statistically significant RFS benefit with pembrolizumab added to metastasis-directed treatment in the studied oligometastatic population. However, the small sample size, Phase II design, and immature OS data should be considered when interpreting its potential clinical application.
KEYNOTE-564: Final Analysis Confirms Sustained DFS and OS Benefits
At ESMO 2026, Toni K. Choueiri presented the final protocol-prespecified analysis of the Phase III KEYNOTE-564 trial (3589RO), evaluating adjuvant pembrolizumab versus placebo in patients with clear-cell RCC at increased risk of recurrence following surgery.
The study randomized 994 patients, including 496 assigned to pembrolizumab and 498 to placebo. The primary endpoint was investigator-assessed disease-free survival (DFS), with OS as a key secondary endpoint. At the February 4, 2026 data cutoff, median follow-up was 85.9 months. The previously established DFS benefit remained consistent, with an HR of 0.68 (95% CI 0.56–0.82). Median DFS was not reached with pembrolizumab versus 68.3 months with placebo.
At seven years, estimated DFS rates were 57.2% versus 44.6%, respectively. The OS benefit was also maintained (HR 0.70; 95% CI 0.53–0.92), with seven-year OS rates of 82.3% with pembrolizumab versus 76.6% with placebo. No new serious treatment-related adverse events were reported at the final analysis. These longer-term findings confirm the durability of the previously demonstrated DFS and OS benefits, providing further evidence supporting adjuvant pembrolizumab in patients with clear-cell RCC at increased risk of recurrence after surgery.
LITESPARK-011: Sustained PFS Benefit With Belzutifan Plus Lenvatinib
The final prespecified analysis of the Phase III LITESPARK-011 trial (3587O), presented by Daniel Heng and published in Annals of Oncology on October 25, 2026, evaluated belzutifan plus lenvatinib versus cabozantinib in patients with advanced clear-cell RCC following anti-PD-(L)1 treatment. The study randomized 747 patients to belzutifan plus lenvatinib (n=371) or cabozantinib (n=376). The dual primary endpoints were progression-free survival (PFS) by blinded independent central review and OS.
At the final analysis, the median time from randomization to the February 2, 2026 data cutoff was 38.8 months. The previously established PFS benefit was maintained, with median PFS of 14.8 months for belzutifan plus lenvatinib versus 10.8 months for cabozantinib (HR 0.74; 95% CI 0.62–0.88). Objective response rates were 53.1% versus 40.2%, while median duration of response was 22.0 versus 11.9 months, respectively. PFS and objective response rate had already met their statistical significance criteria at earlier analyses.
Median OS was 33.7 versus 28.6 months (HR 0.85; 95% CI 0.70–1.03). However, the final OS analysis did not meet the prespecified statistical significance boundary (one-sided p=0.04689; boundary 0.0223). Grade ≥3 treatment-emergent adverse events occurred in 85.4% of patients receiving belzutifan plus lenvatinib versus 83.0% receiving cabozantinib.
The final results confirm sustained PFS and response benefits with belzutifan plus lenvatinib following anti-PD-(L)1 therapy. Although median OS numerically favored the combination, a statistically significant OS improvement was not demonstrated.
Clinical Implications of the ESMO 2026 Findings
The seven studies provide positive efficacy evidence across different genitourinary cancer settings, although the findings vary in their statistical endpoints, maturity, and potential clinical implications. In bladder cancer, VOLGA demonstrated statistically significant improvements in both EFS and OS with perioperative durvalumab plus EV compared with radical cystectomy-based control treatment. The findings support consideration of this regimen in the studied cisplatin-ineligible or cisplatin-declining population, with attention to its safety profile.
In prostate cancer, DASL-HiCaP and the PROTEUS substudy reported significant improvements in metastasis-free survival and event-free survival, respectively, with treatment intensification in different high-risk settings. However, mature OS benefits have not yet been established for these specific analyses. PEACE-1 provided longer-term confirmation of the survival benefit of abiraterone-based treatment in de novo metastatic castration-sensitive disease.
In RCC, PE-PE demonstrated an RFS benefit with pembrolizumab plus metastasis-directed therapy in a randomized Phase II trial, while KEYNOTE-564 confirmed sustained DFS and OS benefits with adjuvant pembrolizumab. LITESPARK-011 maintained previously demonstrated PFS and response benefits, although its final OS endpoint did not meet the prespecified significance criterion.
The clinical implications of these findings differ. Newly positive efficacy trials provide evidence for treatment intensification, whereas mature analyses reinforce previously established benefits. Phase II results and studies without demonstrated OS improvement require interpretation according to their design, endpoints, and safety findings.
The Bottom Line
ESMO 2026 presented significant randomized efficacy findings and longer-term survival evidence across bladder cancer, prostate cancer, and renal cell carcinoma. VOLGA demonstrated improvements in both EFS and OS, while DASL-HiCaP and the PROTEUS substudy reported significant benefits in their respective primary endpoints. PE-PE provided positive Phase II evidence for pembrolizumab combined with metastasis-directed therapy in oligometastatic RCC.
Long-term PEACE-1 findings confirmed the survival benefit of abiraterone-based treatment, and the final KEYNOTE-564 analysis demonstrated sustained DFS and OS benefits with adjuvant pembrolizumab. LITESPARK-011 maintained previously established PFS and response benefits, but its final OS analysis did not achieve statistical significance.
Taken together, these findings provide evidence for treatment intensification and reinforce established therapeutic approaches across selected GU cancer populations. Their application in clinical practice depends on the demonstrated endpoints, safety profiles, maturity of survival data, and patient selection.
Read more about ESMO 2026 Presidential Symposia: From Trial Results to Clinical Implications on OncoDaily.
Sources
- Powles T, Grande E, Simone G, et al. VOLGA, LBA2. Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer. The New England Journal of Medicine. Published October 24, 2026. doi:10.1056/NEJMoa2608323. Original publication.
- Niazi T, Thomas H, Zhang A, et al. DASL-HiCaP/ANZUP1801, LBA4. Darolutamide with androgen deprivation therapy and definitive or salvage locoregional radiation therapy for localized very high-risk prostate cancer. ESMO Congress 2026. Original ESMO abstract.
- Briganti A, et al. PROTEUS substudy, LBA53. Treatment Effect of Perioperative (Neoadjuvant and Adjuvant) Apalutamide plus Androgen-deprivation Therapy Versus Radical Prostatectomy Alone in Patients with High-risk Localized or Locally Advanced Prostate Cancer from the PROTEUS Substudy. European Urology. Published October 2026. doi:10.1016/j.eururo.2026.10.016. Original publication.
- Fizazi K, Foulon S, Carles Galceran J, et al. PEACE-1, 2215O. Long-term overall survival with abiraterone acetate plus prednisone in de novo metastatic castration-sensitive prostate cancer. ESMO Congress 2026. Original ESMO abstract.
- Iacovelli R, et al. PE-PE, LBA88. Perioperative pembrolizumab plus metastasis-directed therapy versus metastasis-directed therapy alone in oligometastatic renal cell carcinoma: randomized Phase II trial. ESMO Congress 2026. Detailed ESMO presentation summary.
- Choueiri TK, et al. KEYNOTE-564, 3589RO. Final protocol-prespecified analysis of adjuvant pembrolizumab in clear-cell renal cell carcinoma. ESMO Congress 2026. Detailed OncoDaily trial report.
- Heng DYC, Schmidinger M, McDermott R, et al. LITESPARK-011, 3587O. Final prespecified analysis of the phase 3 LITESPARK-011 study: belzutifan plus lenvatinib versus cabozantinib for advanced renal cell carcinoma after anti-PD-(L)1 therapy. Annals of Oncology. Published online October 25, 2026. doi:10.1016/j.annonc.2026.10.109. Original publication.
