UPDATE: PROTEUS Substudy Shows Improved Event-Free Survival With Perioperative Apalutamide

New results from a randomised substudy of the phase 3 PROTEUS trial, presented at ESMO 2026, show that adding apalutamide and androgen deprivation therapy (ADT) before and after radical prostatectomy improves outcomes compared with surgery alone in patients with high-risk localised or locally advanced prostate cancer.
The substudy enrolled 408 patients, including 102 receiving perioperative apalutamide plus ADT and 306 undergoing surgery without neoadjuvant systemic treatment. After a median follow-up of 37.8 months, median event-free survival (EFS) was not reached in the treatment group, compared with 19.1 months in the surgery-alone group. At three years, EFS was 63.0% versus 41.4%, representing a 62% relative reduction in the risk of an event or death (HR 0.38).

The risk of metastasis or death was also reduced by 51% (HR 0.49). Median time to subsequent treatment was 46 months versus 12.3 months, while severe adverse events were more frequent with treatment intensification.

Unlike the main PROTEUS trial, which compared apalutamide plus ADT against ADT alone, this substudy directly evaluated the additional benefit over surgery without neoadjuvant treatment.

Although the findings support improved disease control, overall survival benefit has not been established, and longer follow-up is needed to determine the durability of these results.

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