Johnson & Johnson reported positive final results from the Phase 3 PROTEUS trial (NCT03767244), showing that perioperative treatment with ERLEADA® (apalutamide) plus androgen deprivation therapy (ADT) significantly improved both pathological and long-term outcomes in patients with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy.

The findings were presented during a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine. The study provides some of the strongest evidence to date supporting earlier use of systemic therapy in patients with localized disease at high risk of recurrence.

Efficacy Outcomes

The randomized Phase 3 study enrolled 2,109 patients eligible for curative-intent surgery. Patients received apalutamide plus ADT for six months before surgery and continued treatment for six months after radical prostatectomy.

At a median follow-up of 61.7 months, apalutamide plus ADT achieved nearly nine-fold higher rates of pathologic complete response or minimal residual disease compared with ADT alone (8.9% versus 1.0%; OR 10.17; p<0.0001).

The regimen also reduced the risk of metastasis or death by 20% (HR 0.80; p=0.02), with five-year metastasis-free survival rates of 78.2% versus 73.5%. Secondary endpoints supported the benefit, including a 29% reduction in recurrence or death and a median time to subsequent therapy of more than six years compared with approximately 3.5 years in the control arm.

Safety Profile

The safety profile was consistent with previous apalutamide studies. The most common adverse events included hot flushes, urinary incontinence, and erectile dysfunction.

Grade 3 or 4 adverse events occurred in 39.6% of patients receiving apalutamide plus ADT compared with 31.0% of those receiving ADT alone. Treatment discontinuation due to adverse events occurred in 7.4% and 2.7% of patients, respectively. Overall death rates were similar between treatment groups.

Expert Commentary

Mary-Ellen Taplin, M.D., principal investigator of PROTEUS, said the findings demonstrate that integrating systemic therapy before and after surgery can reduce the risk of metastasis or death while potentially lowering the need for future treatment.

Adam Kibel, M.D., Chair of Urology at Mass General Brigham, noted that the results challenge the traditional surgery-only approach for many patients with high-risk disease and support earlier use of androgen receptor pathway inhibition.

Potential Impact on Treatment Paradigms

Despite curative-intent surgery, up to half of patients with high-risk localized prostate cancer experience recurrence, highlighting the need for more effective treatment strategies.

Apalutamide is currently approved for non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer, but its use in localized disease remains investigational. The PROTEUS findings position apalutamide as the first androgen receptor pathway inhibitor to demonstrate a metastasis-free survival benefit in the perioperative treatment of high-risk localized prostate cancer.

If approved in this setting, apalutamide plus ADT could establish perioperative androgen receptor blockade as a new treatment paradigm for patients at high risk of recurrence following surgery.

Reference

Johnson & Johnson’s Phase 3 prostate cancer study shows ERLEADA® (apalutamide) before and after surgery significantly reduces risk of metastasis or death, breaking a decades-long treatment paradigm