ESMO 2026: New Data Advance Prostate, Kidney, and Bladder Cancer Care

Several studies presented at the 2026 European Society for Medical Oncology (ESMO) Congress explored treatment intensification and biomarker assessment across genitourinary (GU) cancers. Findings included improved event-free survival (EFS) with perioperative apalutamide (Erleada) plus androgen deprivation therapy (ADT) in high-risk localized prostate cancer, updated survival results with capivasertib (Truqap) in PTEN-deficient prostate cancer, and long-term overall survival (OS) data with abiraterone (Zytiga) in metastatic disease. Additional analyses examined belzutifan (Welireg)-based treatment in advanced renal cell carcinoma (RCC) and circulating tumor DNA (ctDNA) in muscle-invasive bladder cancer (MIBC).

Perioperative Apalutamide Improves EFS in High-Risk Prostate Cancer

In the PROTEUS substudy (NCT03767244), perioperative apalutamide plus ADT improved EFS compared with radical prostatectomy plus pelvic lymph node dissection alone in patients with high-risk localized or locally advanced prostate cancer.¹

Among 408 randomly assigned patients, median EFS was not reached with apalutamide plus ADT vs 19.1 months with surgery alone after a median follow-up of 37.8 months (HR, 0.38; 95% CI, 0.26-0.55; P < .0001). Metastasis-free survival also favored combination treatment (HR, 0.49; 95% CI, 0.26-0.90).

At 3 years, 35% of patients receiving apalutamide plus ADT required subsequent treatment compared with 68% receiving surgery alone. Grade 3 or 4 adverse events occurred in 30.7% vs 21.7%, respectively. The findings support further consideration of perioperative treatment intensification, although longer follow-up is needed to characterize OS.

CAPItello-281 Reports Updated Survival Findings in PTEN-Deficient Prostate Cancer

An updated analysis of the phase 3 CAPItello-281 trial (NCT04493853) evaluated capivasertib plus abiraterone vs placebo plus abiraterone in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer.²

Among 1012 patients, the ad hoc analysis, with a data cutoff of March 9, 2026, showed median OS of 57.4 months with capivasertib plus abiraterone vs 46.5 months with placebo plus abiraterone (HR, 0.82; 95% CI, 0.68-0.99; nominal P = .044). Median radiographic progression-free survival was 35.5 vs 26.0 months, respectively (HR, 0.83; 95% CI, 0.70-0.99; nominal P = .033).

However, the updated OS analysis was descriptive and did not meet the prespecified alpha-controlled threshold for statistical significance. The results therefore provide additional evidence of a potential benefit but should not be interpreted as a statistically significant OS improvement.

PEACE-1 Shows Long-Term Survival Benefit With Abiraterone

Long-term follow-up from the phase 3 PEACE-1 trial (NCT01957436) reinforced the survival benefit associated with adding abiraterone acetate plus prednisone to standard treatment for de novo metastatic castration-sensitive prostate cancer.³

After a median follow-up of 7.7 years, abiraterone was associated with improved OS compared with regimens without abiraterone (HR, 0.75; 95% CI, 0.65-0.87; P = .0001). Median OS was 4.6 years with standard of care (SOC), 4.6 years with SOC plus radiotherapy, 5.7 years with SOC plus abiraterone, and 6.4 years with SOC plus radiotherapy and abiraterone.

Among 710 patients whose SOC included ADT plus docetaxel, adding abiraterone increased median OS from 4.4 to 6.2 years (HR, 0.68; 95% CI, 0.56-0.82). The 8-year OS rate was 40.3% with triplet therapy vs 27.1% with ADT plus docetaxel. The benefit associated with triplet therapy was observed across metastatic-volume subgroups, with no significant interaction by disease extent.

Belzutifan Plus Lenvatinib Maintains PFS Benefit in Advanced RCC

The final analysis of the phase 3 LITESPARK-011 trial (NCT04586231) evaluated belzutifan plus lenvatinib vs cabozantinib in advanced clear cell RCC after anti–PD-L1 therapy.⁴

Among 747 patients, after a median follow-up of 38.8 months, median progression-free survival (PFS) was 14.8 months with belzutifan plus lenvatinib vs 10.8 months with cabozantinib (HR, 0.74; 95% CI, 0.62-0.88). Objective response rates were 53.1% vs 40.2%, and median duration of response was 22.0 vs 11.9 months.

Median OS was 33.7 vs 28.6 months (HR, 0.85; 95% CI, 0.70-1.03). However, the comparison did not meet the prespecified statistical significance boundary. Grade 3 or higher treatment-emergent adverse events occurred in 85.4% and 83.0% of patients, respectively.

ctDNA Analysis Explores Outcomes With Perioperative Therapy in MIBC

An exploratory analysis of the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) assessed ctDNA status in patients with cisplatin-eligible MIBC receiving perioperative enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) or neoadjuvant cisplatin and gemcitabine, followed by surgery.⁵

Among patients with evaluable presurgical samples who were ctDNA-positive before treatment, ctDNA clearance was observed in 82.1% with enfortumab vedotin plus pembrolizumab vs 66.7% with chemotherapy. Before surgery, ctDNA positivity was 13.0% vs 19.7%, respectively; after surgery, the rates were 4.8% vs 13.5%.

Patients with negative ctDNA status or ctDNA clearance had more favorable EFS and pathologic complete response outcomes. The EFS benefit with enfortumab vedotin plus pembrolizumab was observed across ctDNA subgroups, although some subgroup estimates had confidence intervals crossing 1. These exploratory findings do not establish ctDNA as a basis for omitting surgery or other planned treatment.

Together, the studies highlight ongoing efforts to improve outcomes through treatment intensification in prostate and kidney cancers and to refine response assessment in bladder cancer.

REFERENCES

1. Briganti A, Steuber T, Shore ND, et al. Perioperative apalutamide (APA) plus androgen-deprivation therapy (ADT) with radical prostatectomy plus pelvic lymph node dissection (RP + PLND) vs RP + PLND alone in patients with high-risk localized or locally advanced prostate cancer: PROTEUS substudy. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA53.

2. Fizazi K, Clarke NW, De Santis M, et al. Capivasertib plus abiraterone vs placebo plus abiraterone in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer: updated overall survival from CAPItello-281. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA56.

3. Fizazi K, Foulon S, Galceran JC, et al. Long-term overall survival with abiraterone acetate plus prednisone in the PEACE-1 phase 3 trial for de novo metastatic castration-sensitive prostate cancer. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 2215O.

4. Heng DY, McDermott RS, Park SH, et al. Final analysis of the phase 3 LITESPARK-011 study: belzutifan plus lenvatinib versus cabozantinib for advanced renal cell carcinoma after anti–PD-(L)1 therapy. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 3587O.

5. Chatzkel JA, Galsky MD, Gomez de Liano A, et al. ctDNA analysis of the phase 3 KEYNOTE-B15 trial: Neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab for participants with muscle-invasive bladder cancer who are eligible for cisplatin. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 4734O.