The UroOnc Minute: Perioperative Treatment for High-Risk Localized Prostate Cancer, With Keyan Salari, MD, PhD

Welcome back to The UroOnc Minute!

In this episode of The UroOnc Minute, host Adam B. Weiner, MD, is joined by Keyan Salari, MD, PhD, to discuss results from the phase 3 PROTEUS trial (NCT03767244), which were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.¹ The conversation explores why the trial's positive results have generated significant enthusiasm within the urologic oncology community and what its findings could mean for the management of patients with high-risk localized prostate cancer.

Salari begins by placing the PROTEUS trial into historical context, noting that investigators have spent decades searching for strategies to reduce recurrence following radical prostatectomy in patients with high-risk disease. He reviews how earlier attempts using androgen deprivation therapy (ADT) and chemotherapy failed to meaningfully improve long-term outcomes, setting the stage for the evaluation of apalutamide plus ADT administered before and after surgery. The trial met its co-primary end points, showing that percentage of patients with a pathological complete response or minimal residual disease was significantly higher in the apalutamide group than in the placebo group (8.9% vs. 1.0%; OR, 10.17; 95% CI, 5.27 to 19.64; P < .001), as well as the percentage of patients with metastasis-free survival (probability of metastasis-free survival at 5 years, 78.2% vs. 73.5%; HR for distant metastasis or death, 0.80; 95% CI, 0.67 to 0.96; P = .02).

The conversation then shifts to the practical implications of incorporating this approach into clinical practice. Weiner and Salari examine how the regimen compares with current treatment paradigms for high-risk localized disease and discuss which patients may derive the greatest benefit. Salari emphasizes that the therapy may be particularly well suited for individuals with very high-risk features, including those with pelvic lymph node involvement, for whom recurrence is highly likely. He also highlights one of the trial's most clinically meaningful findings: delaying the need for subsequent therapy by nearly 3 years (median, 74.2 months vs. 41.5 months; HR, 0.65; 95% CI, 0.57 to 0.73; P < .001, an outcome that may translate into meaningful benefits for carefully selected patients.

Finally, the episode looks ahead to the questions that remain unanswered. Salari discusses the importance of ongoing analyses comparing the perioperative regimen with surgery alone, as well as the need for longer-term overall survival data. He also underscores the value of patient-reported outcomes, emphasizing that understanding how patients experience intensified therapy will be critical to shared decision-making and the role for this regimen in clinical practice.

REFERENCE

1. Taplin ME, Gleave M, Shore ND, et al. Perioperative Apalutamide in High-Risk Localized Prostate Cancer. N Engl J Med. 2026. doi: 0.1056/NEJMoa2603878