A clinical trial involving more than 2,100 men with aggressive prostate cancer has shown that adding a drug called apalutamide to standard hormone therapy—both before and after surgery—dramatically reduces the risk of cancer spreading and death. The findings, led by Dr. Mary-Ellen Taplin at Dana-Farber Cancer Institute and Dr. Adam Kibel at Mass General Brigham, represent what researchers are calling a potential shift in how high-risk prostate cancer is treated globally.
Every year, more than 330,000 people are diagnosed with prostate cancer. Up to 20% of them have an aggressive form that carries a significant risk of returning after initial treatment. Currently, doctors treat these patients with surgery, radiation, or both, combined with hormone therapy—a regimen that works well for some but leaves others vulnerable. Remarkably, up to half of patients relapse within five years, creating an urgent need for more effective approaches.
The PROTEUS trial, a rigorous randomized and double-blind study, enrolled 2,109 patients with newly diagnosed high-risk localized or locally advanced prostate cancer. For six months before surgery and six months after, participants received either apalutamide—a next-generation drug that blocks androgen pathways—plus standard hormone therapy, or a placebo plus hormone therapy. All underwent radical prostatectomy with pelvic lymph-node removal.
The results were striking. After a median follow-up of 61.7 months, patients receiving apalutamide plus hormone therapy experienced a 20% reduction in the risk of metastasis or death compared to those on hormone therapy alone. The five-year probability of remaining metastasis-free was 78.2% in the apalutamide group versus 73.5% in the control group—a meaningful difference for men facing a cancer known for its aggressiveness.
Perhaps more remarkable was the drug's effect on what surgeons find when they remove the prostate. Patients treated with apalutamide were nine times more likely to have little to no visible cancer remaining in the surgical specimen. Nearly 9% of those receiving the drug achieved a pathologic complete response or minimal residual disease—meaning surgeons found almost no cancer cells—compared to just 1% in the comparison group. This shift in what doctors see under the microscope translates into tangible benefit: the treatment delayed the need for subsequent therapy by an average of 33 months.
"This type of treatment regimen that combines systemic therapy with surgery is standard in other aggressive cancers and now has proven benefit for patients with high-risk localized or locally advanced prostate cancer," said Taplin in a statement. The trial's findings were presented at the American Society for Clinical Oncology Annual Meeting in Chicago and published in the New England Journal of Medicine, two of the most prestigious venues in cancer research.
What makes this discovery significant is its timing. Prior research from Taplin's team had suggested that intensive hormone therapy before surgery showed promise, which led researchers to test whether apalutamide—already approved for metastatic and nonmetastatic castration-resistant prostate cancer—could improve outcomes even earlier in the disease course. The PROTEUS results confirm that approach works. Side effects were consistent with what researchers have observed in previous studies, meaning the added benefit did not come at the cost of unexpected harm.
For men diagnosed with high-risk prostate cancer who are still in a window where cure is possible, this trial offers new hope that combining powerful systemic therapy with traditional surgery can reshape their odds.