An international phase 3 clinical trial that treated patients with high-risk localised and locally advanced prostate cancer with apalutamide — a next-generation neoadjuvant androgen-receptor pathway inhibitor (ARPI) — plus hormone therapy before and after prostate cancer surgery, was further validated by a substudy demonstrating a reduced risk of metastasis or death compared with standard of care.

The substudy, co-led by principal investigator Mary-Ellen Taplin, MD, medical oncologist at Dana-Farber Cancer Institute, was presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain and published in European Urology.

Alberto Briganti, MD, PhD, Professor of Urology at Vita-Salute San Raffaele University in Milan, Italy, presented the data at ESMO.

Previous Dana-Farber research led by Taplin, presented earlier this year at the American Society for Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine, found that apalutamide plus androgen-deprivation hormone therapy (ADT) prior to and after surgery showed significant promise for patients with high-risk localised prostate cancer.

Patients treated with the apalutamide plus hormone therapy regimen were nine times more likely to have little to no cancer present at surgery, reduced the risk of metastases or death by 20% and delayed subsequent therapy by 33 months compared to ADT alone.

The substudy compared the novel perioperative approach to standard of care, radical prostatectomy alone.

“Following the presentation of the PROTEUS results at ASCO, an important question remained: how does this regimen compare with standard of care prostatectomy? Addressing that question is essential to understanding the full clinical significance of these findings and determining how they can best inform treatment decisions for patients with high-risk localised prostate cancer,” said Taplin. “This substudy demonstrated superior efficacy of perioperative apalutamide plus ADT over radical prostatectomy alone in high-risk localised/locally advanced prostate cancer, reinforcing the PROTEUS main study findings.”

PROTEUS substudy is a 1:3 randomised trial that included 408 patients with newly diagnosed high-risk localised or locally advanced prostate cancer designed to compare apalutamide plus ADT before and after surgery to standard of care radical prostatectomy.

Apalutamide is approved for use in metastatic castration-sensitive prostate cancer and for nonmetastatic castration-resistant prostate cancer. 

Participating patients received apalutamide plus ADT for 6 months before and after radical prostatectomy with pelvic lymph-node dissection or standard or prostatectomy alone.

The study’s primary endpoint was event-free survival (events included PSA, clinical, PSMA-PET or conventional imaging relapse).

After a median follow-up of 37.8 months, the combination of apalutamide plus ADT and prostatectomy resulted in a 62 percent improvement in event-free survival and a 51 percent reduced risk of metastasis or death.

The combination reduced the risk of starting a subsequent therapy by 71 percent, and 50 percent fewer patients started subsequent therapy by 3 years. 

Side effects were consistent with data from previously reported studies.

“Combined evidence from the main and substudy support perioperative apalutamide plus ADT and prostatectomy as a potential treatment of choice in patients fit for surgery and systemic therapy,” said Taplin. 

Source: Dana-Farber Cancer Institute