Perioperative Apalutamide Plus ADT Cuts Metastasis Risk 51% Versus Surgery Alone in High-Risk Prostate Cancer

The substudy, presented at ESMO 2026 and published in European Urology, enrolled patients with high-risk localized or locally advanced prostate cancer and compared the perioperative ARPI regimen directly against standard radical prostatectomy. Primary endpoint was event-free survival incorporating PSA, clinical, and imaging relapse. Absolute metastasis-free survival benefit reached 51% relative risk reduction, with 71% lower likelihood of needing subsequent therapy and 50% fewer patients starting such therapy by three years.

These findings build on the earlier PROTEUS main study reported in NEJM that demonstrated pathologic complete response rates nine times higher with the combination. By isolating the perioperative arm against surgery alone, the substudy addresses a key gap left by prior trials that used ADT monotherapy controls. It aligns with precision-medicine trends favoring intensified androgen-receptor blockade in high-risk localized disease before systemic spread occurs.

Longer follow-up is required to determine whether the 51% metastasis-free survival gain translates into overall survival improvement, and whether genomic biomarkers can identify the patients deriving greatest benefit. Ongoing trials testing similar ARPIs in the same setting will clarify class effects and optimal duration.

Side-effect profiles remained consistent with known ARPI data, supporting feasibility, yet cost-effectiveness and quality-of-life trade-offs need prospective evaluation before widespread adoption.