Results from the phase 3 PROTEUS study found that for people with localised high-risk prostate cancer, treatment with apalutamide and androgen deprivation therapy (ADT) along with surgery could delay or prevent worsening of the disease, with few additional side effects, better than ADT and surgery.

The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 to June 2 in Chicago.

“This study investigated an intensified androgen deprivation treatment to reduce tumours, eliminate possible microscopic disease, and improve long-term outcomes. The favourable results support apalutamide plus androgen deprivation therapy treatment with radical prostatectomy as a possible new option for people with localised high-risk prostate cancer,” said lead study author Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute.

The trial was designed to evaluate whether administering apalutamide and ADT before and after surgery reduced the development of metastases compared to placebo and ADT.

The study included 2,109 participants across 118 hospitals globally.

The median age of participants was 66, and 69.4% were White, 19.3% were Asian, and 3.7% were Black or African American.

Participants had a median prostate-specific antigen (PSA) value of 14.8 ng/ml, and a majority had a Gleason score of 8 or higher, indicating high-risk disease.

They had not gotten treatment for the cancer.

Participants were divided into 2 groups. All participants had a radical prostatectomy and received ADT for 6 months before and 6 months after surgery.

The two groups differed in the treatment they received alongside ADT: 1,057 got apalutamide, while 1,052 got a placebo.

Key Findings

• After a median follow-up of about 62 months, results showed that giving apalutamide before and after radical prostatectomy improved treatment outcomes for people with high-risk prostate cancer. 
• People who got neoadjuvant apalutamide were about 10 times more likely to have a major reduction of tumour cells by the time they got prostate surgery: 8.9% of people in the apalutamide group and 1% in the placebo group achieved pathologic complete response or minimal residual disease. 
• Participants who got apalutamide had a 29% lower risk the prostate cancer would come back.
• Neoadjuvant and adjuvant apalutamide treatment prolonged the median event-free survival from 38.4 months in the placebo group to 57.1 months in the apalutamide group.
• Apalutamide treatment lowered the risk of metastasis by 20% compared to a placebo, and it improved 5-year metastasis-free survival from 73.5% in the placebo group to 78.2% in the apalutamide group.

Compared to the placebo group, the apalutamide group was more likely to have severe and life-threatening (grades 3 to 4) adverse events, which occurred in 39.6% and 31% of participants, respectively.

The most common adverse events in both groups were a build-up of lymphatic fluid (lymphocele) and urinary tract infection.

Pulmonary embolism also occurred in the placebo group. Rashes were the most common reason people discontinued treatment in the apalutamide group.

“This is the first convincing randomised control trial demonstrating improvement in clinically meaningful endpoints in patients with high-risk localised prostate cancer treated with radical prostatectomy. With pathologic complete response rates near 9% and metastasis-free survival improvements of 20% compared with androgen deprivation therapy alone, the addition of apalutamide to androgen deprivation therapy clearly improves outcomes in surgical patients at high risk for relapse. That said, we haven’t yet compared it directly to current options like upfront surgery or the combination of radiation and androgen deprivation therapy,” said William K. Oh, MD, Yale School of Medicine and an ASCO Expert in genitourinary cancers. 

Researchers will use PROTEUS data to evaluate the association between the extent of tumour shrinkage and long-term outcomes.

Further analyses will investigate biomarkers to help predict which patients will benefit from apalutamide and if the treatment may eventually stop working.

In addition, researchers will analyse patient-reported outcomes to understand the effects of treatment on quality of life.

Watch the related interview here.

Source: ASCO