Erleada before and after surgery cuts recurrence or death risk by 62% in high-risk prostate cancer – Johnson & Johnson

Johnson & Johnson announced new results from the Phase 3 PROTEUS substudy that directly compared the investigational use of apalutamide plus androgen deprivation therapy (ADT), given for six months before and after surgery, with radical prostatectomy alone in patients with high-risk localized or locally advanced prostate cancer.
The apalutamide plus ADT regimen reduced the risk of disease recurrence or death by 62 percent compared with surgery alone. The regimen also showed a numerical improvement in metastasis-free survival (MFS), with a 51 percent lower risk of metastasis or death. Patients receiving apalutamide plus ADT also went longer before needing subsequent therapy.

These substudy findings build on the primary PROTEUS results presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and evaluate a remaining clinical question by directly comparing perioperative apalutamide plus ADT with surgery alone, a longstanding standard of care. The new results were presented at the European Society for Medical Oncology (ESMO) Congress 2026 (#LBA53). The accompanying manuscript has been accepted for publication by European Urology.

The burden of recurrence in high-risk localized prostate cancer

For patients with high-risk localized or locally advanced prostate cancer, surgery has long been a standard of care performed with curative intent. Yet nearly half of patients will see their cancer return and require additional treatment. Recurrence can mean facing further therapy and the continued risk that the disease will spread, underscoring the need for approaches that can improve outcomes earlier in the course of disease. Apalutamide blocks androgen hormones from binding to their receptor, which can help slow prostate cancer progression. It is currently approved for use in advanced prostate cancer, including cases where the disease has spread (metastatic castration-sensitive) or is no longer responding to certain hormone therapies (non-metastatic castration-resistant prostate cancer).

Expert and company perspectives on improving outcomes earlier in high-risk prostate cancer

“Radical prostatectomy has long been a cornerstone of curative-intent treatment for high-risk localized prostate cancer, yet recurrence remains a concern for patients with aggressive disease,” said Alberto Briganti, M.D., Professor of Urology and Urologic Surgeon at IRCCS San Raffaele Hospital, Milan. “In this substudy, median event-free survival was 19.1 months with surgery alone, highlighting the challenges these patients continue to face despite treatment intended to cure their cancer. The reduction in the risk of recurrence and metastases after radical prostatectomy seen with apalutamide plus androgen deprivation therapy suggests we may be able to build on surgery and help more patients achieve lasting disease control.”

“For people with high-risk early prostate cancer, finishing surgery doesn’t necessarily mean the uncertainty is over. The possibility of recurrence can weigh heavily on patients and their families, even as they try to move forward with their lives,” said Courtney Bugler, President and CEO of ZERO Prostate Cancer, a leading prostate cancer patient advocacy organization in the U.S. “The possibility of helping more people remain free from disease recurrence, and potentially avoid or delay additional treatment, is incredibly meaningful. More time without another treatment can mean more time focused on family, work and life, rather than what comes next for their cancer.”

“The primary PROTEUS study showed the potential of treating high-risk prostate cancer earlier with apalutamide plus androgen deprivation therapy. We designed this substudy to take that evidence further by evaluating the regimen against surgery alone, a longstanding standard of care for these patients,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “These findings provide important additional insight into what this approach could mean for patients and reinforce why we continue to investigate ways to improve outcomes earlier in the course of disease.”

Perioperative treatment demonstrates improvement in event-free survival

The PROTEUS substudy evaluated apalutamide plus ADT before and after surgery compared with radical prostatectomy alone in 408 patients with newly diagnosed, non-metastatic, high-risk localized or locally advanced prostate cancer who were fit for surgery and systemic therapy. The primary endpoint was 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, apalutamide plus ADT significantly improved EFS, reducing the risk of recurrence or death by 62 percent compared with surgery alone (hazard ratio [HR], 0.38; 95 percent confidence interval [CI], 0.26-0.55; p<0.0001). Median EFS was not reached with apalutamide plus ADT, compared with 19.1 months with surgery alone. At three years, 63 percent of patients receiving apalutamide plus ADT remained event-free compared with 41.4 percent of those undergoing surgery alone.

Numerical improvements were also observed across secondary and exploratory endpoints. For the secondary endpoint of MFS, apalutamide plus ADT showed a 51 percent lower risk of distant metastasis or death (HR, 0.49; 95 percent CI, 0.26-0.90; nominal p=0.0193). For the exploratory endpoint of time to first subsequent therapy, the regimen showed a 71 percent lower risk of needing subsequent treatment (HR, 0.29; 95 percent CI, 0.20-0.43; nominal p<0.0001). At three years, 64.6 percent of patients receiving apalutamide plus ADT remained free from subsequent therapy compared with 32 percent undergoing surgery alone. Additional follow-up is underway to evaluate overall survival.

The safety profile was consistent with the primary PROTEUS study results. Grade 3 or 4 treatment-emergent adverse events occurred in 31 percent of patients receiving apalutamide plus ADT and 22 percent receiving surgery alone. No treatment-emergent adverse events leading to death were reported in either arm. The most common adverse events with apalutamide included hot flush (64 percent) and urinary incontinence (63 percent).

Apalutamide plus ADT has not been approved by regulatory authorities for the treatment of high-risk localized or locally advanced prostate cancer. These findings add to the growing body of evidence evaluating the potential of treating selected patients with high-risk prostate cancer earlier in the course of disease.

About the PROTEUS substudy
The PROTEUS substudy is a randomized, open-label study evaluating perioperative apalutamide plus androgen deprivation therapy (ADT) compared with radical prostatectomy alone in patients with high-risk localized or locally advanced prostate cancer who are candidates for radical prostatectomy. The substudy was designed to further evaluate the efficacy and safety of adding apalutamide plus ADT before and after surgery compared with surgery alone. A total of 408 patients were randomized to one of two treatment groups, with 102 receiving apalutamide plus ADT and 306 undergoing radical prostatectomy alone. Patients receiving apalutamide plus ADT were treated for six 28-day cycles before radical prostatectomy with pelvic lymph node dissection and for six cycles after surgery, with apalutamide paused two weeks before and resumed four weeks after radical prostatectomy with pelvic lymph node dissection. Apalutamide was administered orally at 240 mg once daily. Patients in the comparator arm underwent radical prostatectomy with pelvic lymph node dissection followed by standard institutional practice or observation. The primary endpoint is event-free survival (EFS), defined as the time to biochemical failure, local or regional recurrence, distant metastasis or death. Secondary endpoints include prostate-specific antigen (PSA)-free survival and metastasis-free survival (MFS), with exploratory endpoints including time to first subsequent systemic therapy and overall survival.