Alberto Briganti, MD, PhD, on the PROTEUS substudy in high-risk prostate cancer

In this video, Alberto Briganti, MD, PhD, of Vita-Salute San Raffaele University in Milan, Italy, discusses findings from the PROTEUS substudy evaluating perioperative apalutamide (Erleada) plus androgen deprivation therapy (ADT) compared with radical prostatectomy (RP) alone in patients with high-risk localized or locally advanced prostate cancer. These findings were presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain.

The primary PROTEUS trial (NCT03767244) demonstrated that perioperative apalutamide plus ADT improved pathological response and metastasis-free survival (MFS) compared with placebo plus ADT in patients undergoing RP with pelvic lymph node dissection. However, the main study did not include a control arm receiving surgery alone, the standard treatment approach without neoadjuvant therapy. The prespecified substudy addressed this limitation by directly comparing perioperative apalutamide plus ADT with immediate RP alone in 408 patients with high-risk localized or locally advanced prostate cancer.

The substudy met its primary end point of event-free survival (EFS), defined as the time to biochemical failure, local or regional recurrence, distant metastasis, or death. At a median follow-up of 37.8 months, median EFS was not reached in the apalutamide plus ADT group compared with 19.1 months in the RP-alone group, corresponding to a 62% reduction in the risk of recurrence or death (HR, 0.38; 95% CI, 0.26 to 0.55; P < .0001). The combination also reduced the risk of metastasis or death by 51% (HR, 0.49; 95% CI, 0.26 to 0.90) and the risk of requiring subsequent therapy by 71% (HR, 0.29; 95% CI, 0.20 to 0.43).

Grade 3 or 4 adverse events occurred in 30.7% of patients receiving apalutamide plus ADT compared with 21.7% of those undergoing RP alone. Briganti also noted that testosterone suppression could delay prostate-specific antigen (PSA) increases and subsequent recurrence detection by prostate-specific membrane antigen positron emission tomography (PSMA-PET). However, additional landmark analyses showed that the EFS benefit was maintained over time, including after testosterone recovery.

Briganti said the findings from the PROTEUS main study and substudy together provide evidence for the potential role of perioperative systemic therapy in selected patients with high-risk localized or locally advanced prostate cancer. He emphasized that treatment decisions should account for appropriate patient selection and the potential adverse effects of both systemic therapy and surgery. As clinicians consider integrating perioperative apalutamide plus ADT into treatment approaches, the results offer a direct comparison with surgery alone while highlighting the importance of balancing oncological benefit with treatment-related risks.

REFERENCE
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 (pts) with high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): PROTEUS substudy. Presented at: 2026 European Society for Medical Oncology Congress. October 23-27, 2026. Madrid, Spain. LBA53. https://cslide.ctimeetingtech.com/esmo2026/attendee/confcal/session/list?q=proteus