PROTEUS Clinical Trial Results Presented at ESMO Congress 2026
An international clinical trial evaluating apalutamide combined with hormone therapy before and after surgery for high-risk localized and locally advanced prostate cancer has demonstrated a reduced risk of metastasis or death compared to standard care. The findings from the PROTEUS substudy were presented at the European Society for Medical Oncology Congress 2026 in Madrid, Spain, and published in European Urology.
“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 localized prostate cancer,” said Mary-Ellen Taplin, MD, a medical oncologist at Dana-Farber Cancer Institute and principal investigator.
Trial Design and Patient Outcomes
The PROTEUS substudy operated as a 1:3 randomized trial tracking 408 patients with newly diagnosed high-risk localized or locally advanced prostate cancer. Participants received either apalutamide plus androgen-deprivation therapy for six months before and after radical prostatectomy with pelvic lymph-node dissection, or standard-of-care radical prostatectomy alone. Alberto Briganti, MD, PhD, a professor of urology at Vita-Salute San Raffaele University in Milan, Italy, presented the data in Madrid.
After a median follow-up of 37.8 months, the combination regimen yielded a 62 percent improvement in event-free survival and a 51 percent reduced risk of metastasis or death. Events tracked in the primary endpoint included prostate-specific antigen relapse, clinical relapse, and findings on PSMA-PET or conventional imaging. The combination treatment also lowered the risk of starting subsequent therapy by 71 percent, resulting in 50 percent fewer patients initiating subsequent therapy by 3 years. Side effects aligned with data recorded in previous evaluations of the drug.
Comparison with Previous Research
The new substudy builds upon earlier findings from the PROTEUS trial led by Taplin, which were presented at the American Society for Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. That initial research compared apalutamide plus androgen-deprivation therapy directly against androgen-deprivation therapy alone. In that comparison, patients receiving the combination regimen were nine times more likely to have little to no cancer present at the time of surgery, experienced a 20 percent reduction in the risk of metastases or death, and delayed subsequent therapy by 33 months.
“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,” Taplin said.
Frequently Asked Questions About the PROTEUS Substudy
What is apalutamide and how does it function in this treatment?
Apalutamide is a next-generation neoadjuvant androgen-receptor pathway inhibitor. It is already approved for use in metastatic castration-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer. In the PROTEUS trial, it was administered alongside hormone therapy before and after surgery.
Who led the presentation of the substudy data in Madrid?
Alberto Briganti, MD, PhD, a professor of urology at Vita-Salute San Raffaele University in Milan, Italy, presented the substudy data at the European Society for Medical Oncology Congress 2026. Mary-Ellen Taplin, MD, of the Dana-Farber Cancer Institute served as co-lead principal investigator.
How many patients participated in the randomized substudy?
The substudy included 408 patients with newly diagnosed high-risk localized or locally advanced prostate cancer. The trial followed a 1:3 randomization design comparing the combination therapy against standard-of-care radical prostatectomy alone.
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