6 Trials Impacting Treatment Options for Genitourinary Cancers

Key Trials and Recent Approvals in Genitourinary Cancers

The cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, joined with Uromigos podcast cohosts Thomas Powles, MD, MBBS, MRCP, of Barts Cancer Institute, and Brian Rini, MD, FASCO, of Vanderbilt-Ingram Cancer Center, to discuss presentations from the PROTEUS, TALAPRO-3, and EV-302 trials at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026), as well as recent FDA approvals based on the POTOMAC, CAPItello-281, and LITESPARK-022 trials.

PROTEUS

The phase 3 PROTEUS trial evaluated the addition of perioperative apalutamide to androgen deprivation therapy (ADT) and radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer. The ASCO 2026 presentation covered 1057 patients randomized to apalutamide plus ADT and 1052 randomized to placebo plus ADT. 

After a median follow-up of 61.7 months, the rate of pathologic complete response (CR) plus minimal residual disease was 8.9% in the apalutamide arm versus 1% in the placebo arm (OR, 10.17; 95% CI, 5.27-19.64; P < .0001). Apalutamide also significantly improved metastasis-free survival (MFS) compared with placebo (HR, 0.80; 95% CI, 0.67-0.96; P = .0169), with 5-year MFS rates of 78.2% versus 73.5%, respectively. Additional end points, including event-free survival, time to first subsequent treatment, time to distant metastasis, and residual cancer burden all favored apalutamide.

The use of ADT alone is not standard of care for this population and has raised questions about the strength of the control arm in PROTEUS. The study provides the only level 1 evidence for combining surgery and hormone therapy in prostate cancer, and the choice between definitive radiation or surgery ultimately remains a shared decision with each patient, Dr. Rini said. 

TALAPRO-3

Adding talazoparib to enzalutamide significantly improved rPFS and OS for patients with metastatic castration-resistant prostate cancer in the TALAPRO-2 trial. TALAPRO-3 evaluated the combination in patients with mCSPC with HRR gene alterations. 

Talazoparib plus enzalutamide significantly improved rPFS compared with placebo plus enzalutamide (HR, 0.481; 95% CI, 0.357-0.647; P < .0001), with median rPFS not reached versus 45.8 months, respectively. The rPFS benefit was greater in the BRCA-mutated subgroup (HR, 0.368; 95% CI, 0.222-0.609) than in the non-BRCA–mutated subgroup (HR, 0.567; 95% CI, 0.392-0.819). Interim OS analysis favored talazoparib but was not yet statistically significant, according to the ASCO 2026 presentation. 

In Dr. Powles’ opinion, these are the strongest data yet for poly (ADP-ribose) polymerase (PARP) inhibitor therapy in early metastatic prostate cancer, particularly with the benefit maintained for the non-BRCA–mutated, HRR-mutated subgroup. 

CAPItello-281

The CAPItello-281 trial showed capivasertib plus abiraterone significantly improved rPFS versus abiraterone alone for patients with metastatic hormone-sensitive prostate cancer with PTEN deficiency, and the FDA approved the combination on June 12, 2026. At ASCO 2026, authors presented tolerability data and patient-reported outcomes (PROs). 

The capivasertib plus abiraterone and placebo plus abiraterone arms each had 503 patients, of whom 60.9% and 62.8%, respectively, completed the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire. There were no clinically meaningful differences in least-squares mean change from baseline between arms for FACT-P total score (difference, 0.4; 95% CI, −1.97 to 2.78), physical well-being score (difference, −0.4; 95% CI, −0.89 to 0.14), or functional well-being score (difference, −0.3; 95% CI, −1.01 to 0.37). Time to deterioration (TTD) in physical well-being was faster in the capivasertib arm (HR, 1.43; 95% CI, 1.15-1.78), although there were no differences in TTD for total score (HR, 1.10; 95% CI, 0.89-1.37) or functional well-being score (HR, 1.06; 95% CI, 0.86-1.32). 

The rPFS benefit with capivasertib was statistically significant only for patients with 99% to 100% PTEN deficiency, so the use of capivasertib for metastatic hormone-sensitive prostate cancer in the real world may be limited to patients with greater PTEN deficiency, Dr. Rini suggested.

POTOMAC

The phase 3 POTOMAC trial showed durvalumab plus BCG induction and maintenance therapy significantly improved disease-free survival versus BCG alone for patients with BCG-naive, high-risk, non–muscle-invasive bladder cancer (NMIBC). Authors also presented PROs and 5-year OS outcomes at ASCO 2026.

At the data cutoff, with a median follow-up of 72 months, the HR for OS was 0.81 (95% CI, 0.54-1.19), and 5-year OS rates were 87.6% (95% CI, 83.5-90.8) in the durvalumab group versus 86.3% (95% CI, 82.1-89.6) in the BCG-only group. Median OS was not reached in either arm. Both arms had deterioration from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 mean baseline scores, and the durvalumab arm PROs suggested clinically meaningful deterioration for fatigue, although the difference between arms was small, according to the presentation. 

While the FDA approved the combination on May 28, 2026, weighing the relative benefit gained by adding durvalumab in the POTOMAC trial against the potential immunotherapy-related side effects is challenging, Dr. Rini said. This may be a more attractive treatment option for patients who are unlikely to undergo cystectomy, Dr. Powles suggested. 

EV-302

The phase 3 EV-302 trial established EV plus pembro as standard of care for previously untreated locally advanced or metastatic urothelial carcinoma after the combination improved PFS and OS outcomes compared with chemotherapy. At ASCO 2026, Dr. Powles presented 3.5-year follow-up data and an exploratory analysis on patients who achieved a CR after an initial partial response (PR). 

After a median follow-up of 42.8 months, EV plus pembro had a median OS of 33.6 months versus 15.9 months with chemotherapy, with 42-month OS rates of 44% versus 24.6%, respectively (HR, 0.53; 95% CI, 0.45-0.63). Among responders, 45.1% of patients in the EV plus pembro arm achieved a CR versus 32.8% in the chemotherapy arm. Among confirmed CR patients in the EV plus pembro arm, 66.2% had initially achieved a PR and converted to CR after a median of 5 additional treatment cycles (interquartile range, 3-8). 

Although the EV-302 trial represents an important advance over traditional platinum-based chemotherapy, more data are needed to determine the optimal duration of therapy. Before stopping therapy, oncologists should consider each patient’s baseline disease and response characteristics, tolerability, and preferences, Dr. Powles said.

LITESPARK-022

On June 12, 2026, based on the phase 3 LITESPARK-022 trial, the FDA approved adjuvant belzutifan plus pembro for patients with clear cell renal cell carcinoma (ccRCC) with intermediate-high or high risk of recurrence. Just before the approval, authors presented interim trial results at ASCO 2026.

The LITESPARK-022 study randomized 921 patients with ccRCC to pembro plus belzutifan and 902 to pembro plus placebo. After a median follow-up of 28.4 months (range, 15.0-40.1), adding belzutifan significantly improved disease-free survival (DFS; HR, 0.72; 95% CI, 0.59-0.87; P = .0003). Median DFS was not reached in either arm, although the estimated 24-month DFS rate was 80.7% (95% CI, 77.7-83.2) in the belzutifan arm versus 73.7% (95% CI, 70.6-76.6) in the placebo arm. OS data were immature but trended toward greater benefit with pembro plus belzutifan (HR, 0.78; 95% CI, 0.51-1.19; P = .122).

Dr. Rini expressed concern about overtreatment in general with any adjuvant therapy and said he wanted to wait for more mature data before incorporating this intensified adjuvant combination in his own practice. In contrast, Dr. Powles said he has seen belzutifan-related adverse effects resolve after discontinuing the drug and suggested that, if an oncologist already plans to start adjuvant therapy to treat ccRCC, it may be reasonable to initiate and assess the patient’s response.