Findings from a substudy of the phase III PROTEUS trial provided further support for the use of perioperative apalutamide and androgen-deprivation therapy (ADT) before and after surgery for patients with high-risk localized and locally advanced prostate cancer, according to results presented at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA53). During the meeting, Alberto Briganti, MD, PhD, Professor of Urology at Vita-Salute San Raffaele University in Milan, Italy, presented the results of the substudy.
“Following the presentation of the PROTEUS results at the 2026 ASCO Annual Meeting, an important question remained: how does this regimen compare with standard-of-care prostatectomy? Addressing that question is essential to understanding the full clinical significance of these findings and determining how they can best inform treatment decisions for patients with high-risk localized prostate cancer,” said study co-lead and PROTEUS principal investigator Mary-Ellen Taplin, MD, medical oncologist at Dana-Farber Cancer Institute. “This substudy demonstrated superior efficacy of perioperative apalutamide plus ADT over radical prostatectomy alone in high-risk localized/locally advanced prostate cancer, reinforcing the PROTEUS main study findings.”
Background and Study Methods
Findings from the main phase III PROTEUS study showed that perioperative apalutamide added to ADT improved the outcomes of patients with high-risk localized or locally advanced prostate cancer who underwent radical prostatecomy as compared with ADT plus placebo.
A prespecificed substudy of PROTEUS compared apalutamide and androgen deprivation therapy plus radical prostatectomy and pelvic lymph node dissection with immediate radical prostatectomy and pelvic lymph node dissection.
The substudy included patients with nonmetastatic high-risk localized or locally advanced prostate cancer who were candidates for radical prostatectomy (n = 408). Participants were randomly assigned 1:3 to receive open-label apalutamide 240 mg/day with six cycles of ADT before and after radical prostatectomy and pelvic lymph node dissection (n = 102) vs surgery alone (n = 306).
The primary endpoint of the substudy was event-free survival, which was defined as time to first biochemical failure event, local/regional recurrence, distant metastasis, or death. Secondary and exploratory endpoints matched the main PROTEUS study, including first subsequent treatment, distant metastasis, and safety.
Key Findings
Patients were followed for a median of 37.8 months. The median event-free survival was not met in the systemic therapy plus surgery arm compared with 19.1 months in the surgery alone arm (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.26–0.55; P < .0001).
Metastasis-free survival also favored the apalutamide and ADT arm (HR = 0.49; 95% CI = 0.26–0.90).
At 3 years, 35% of patients in the systemic therapy arm received subsequent therapy as compared with 68% who underwent surgery alone. The risk of needing subsequent therapy was reduced significantly with the addition of apalutamide and ADT (HR = 0.29; 95% CI = 0.20–0.43).
The rates of grade 3 or 4 adverse events were 30.8% with added systemic therapy and 21.7% without. The adverse events experienced were consistent with prior reports.
“Combined evidence from the main and substudy support perioperative apalutamide plus ADT and prostatectomy as a potential treatment of choice in patients fit for surgery and systemic therapy,” Dr. Taplin said.
DISCLOSURES: Study funding came from Johnson & Johnson. For full disclosures of the study authors, visit ctimeetingtech.com/esmo2026.
