Results from the phase III PROTEUS trial indicate that adding the androgen receptor pathway inhibitor apalutamide to androgen-deprivation therapy (ADT) before and after radical prostatectomy significantly improves outcomes for patients with localized high-risk prostate cancer, according to findings presented during the Plenary Session at the 2026 ASCO Annual Meeting (Abstract LBA1).
Study Details
The international study enrolled 2,109 patients (median age = 66 years, interquartile range = 41–89 years) with previously untreated localized high-risk prostate cancer across 118 centers in 18 countries. Participants were randomly assigned to receive either apalutamide plus ADT (n = 1,057) or placebo plus ADT (n = 1,052) for 6 months before and 6 months after radical prostatectomy. The primary objective was to determine whether intensified androgen receptor pathway inhibition could reduce recurrence and metastasis in a population at substantial risk for disease relapse.
Key Takeaways
After a median follow-up of approximately 62 months, investigators reported significant improvements in multiple clinically meaningful endpoints among patients treated with apalutamide. Patients receiving neoadjuvant apalutamide were nearly 10 times more likely to achieve a pathologic complete response or minimal residual disease at surgery than those receiving placebo (8.9% vs 1.0%).
The addition of apalutamide also reduced the risk of disease recurrence by 29%. Median event-free survival improved from 38.4 months in the placebo group to 57.1 months in the apalutamide group. Furthermore, apalutamide lowered the risk of metastasis by 20%, increasing the 5-year metastasis-free survival rate from 73.5% to 78.2%.
“These favorable results support apalutamide plus [ADT] with radical prostatectomy as a possible new option for people with localized high-risk prostate cancer,” said lead author Mary-Ellen Taplin, MD, of Dana-Farber Cancer Institute.
Grade 3 or 4 adverse events occurred more frequently in the apalutamide group than in the placebo group (39.6% vs 31.0%). The most common adverse events in both treatment arms were lymphocele and urinary tract infection. Rash was the leading cause of treatment discontinuation among patients receiving apalutamide.
William K. Oh, MD, of Yale School of Medicine and an ASCO Expert in genitourinary cancers, characterized the findings as the first convincing randomized evidence demonstrating improvement in clinically meaningful outcomes among patients with high-risk localized prostate cancer undergoing radical prostatectomy. He noted that the study showed pathologic complete response rates approaching 9% and meaningful gains in metastasis-free survival, while emphasizing that the regimen has not yet been directly compared with other established treatment strategies, including upfront surgery alone or radiation therapy combined with ADT.
Investigators plan additional analyses to examine correlations between tumor response and long-term outcomes, predictive biomarkers of benefit, mechanisms of resistance, and patient-reported quality-of-life outcomes.
DISCLOSURE: For full disclosures of the study authors, visit coi.asco.org.
