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

PROTEUS Substudy vs RP alone

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with high-risk localised or locally advanced prostate cancer, perioperative apalutamide plus ADT with radical prostatectomy and pelvic lymph node dissection improved event-free survival compared with radical prostatectomy and pelvic lymph node dissection alone.

N

408pacientes

Diseño

Prespecified open-label randomised substudy of PROTEUS in which patients with M0 high-risk localised or locally advanced prostate cancer who were candidates for radical prostatectomy were allocated 1:3 to perioperative apalutamide plus ADT for 6 cycles before and after RP + PLND vs immediate RP + PLND alone (NCT03767244).

Desenlace

Event-free survival, defined as time to first event of biochemical failure, local/regional recurrence, distant metastasis or death.

ResultadoMedian EFS not reached with apalutamide plus ADT vs 19.1 mo with RP alone; HR 0.38 (95% CI 0.26-0.55; P<0.0001) at a median follow-up of 37.8 mo. MFS by conventional or PSMA PET imaging HR 0.49 (95% CI 0.26-0.90). Subsequent therapy at 3 y 35% vs 68%, with risk of needing subsequent therapy reduced by 71% (HR 0.29; 95% CI 0.20-0.43). Adjuvant radiotherapy 3.9% vs 14.4% and salvage radiotherapy 15.7% vs 27.8%. Grade 3/4 adverse events 30.7% vs 21.7%.

Briganti A, Steuber T, Shore ND, et al. Presented at ESMO Congress 2026, abstract LBA53, 24 October. Not yet published.

Discusión y crítica

This randomised substudy supplies the immediate-surgery control that the blinded main study lacked, and it shows a large reduction in EFS events with perioperative apalutamide plus ADT. The trial was open label and EFS includes biochemical failure, so the primary endpoint rests partly on a PSA-based surrogate. Decisions on adjuvant, salvage and subsequent therapy may also have been shaped by knowledge of the assigned arm. The metastasis-free survival benefit has a wide confidence interval, and with a median follow-up of 37.8 months the abstract reports no overall survival or quality-of-life data. The 1:3 allocation leaves only 102 patients in the experimental arm, and grade 3/4 adverse events were more frequent with apalutamide plus ADT.