For Men Facing High-Risk Prostate Cancer Surgery, Adding Apalutamide Cut the Odds of Spread

CATEGORY: MEN’S HEALTH

Taking the hormone-blocking pill apalutamide for six months before and six months after prostate cancer surgery cut the risk of the cancer spreading or of death by 20% in men with high-risk disease. Five years in, 78.2% of men who got the drug were alive with no spread, versus 73.5% of men who had the same surgery and standard hormone treatment with a placebo. That’s a gap of 4.7 percentage points.¹

The Men Surgery Alone Keeps Failing

Removing the prostate can cure cancer that hasn’t left it. For men whose tumors look aggressive on biopsy and imaging, though, the operation often isn’t the end of the story. Up to half of them relapse within five years. The PROTEUS trial asked whether wrapping the surgery in stronger drug treatment could change that. The drug tested, apalutamide, blocks testosterone from reaching cancer cells and is already used for advanced prostate cancer. Every man in the trial also received hormone therapy, treatment that cuts the body’s testosterone supply, which prostate tumors feed on.

Identical Bottles for 2,109 Men

Researchers enrolled 2,109 newly diagnosed men with high-risk localized or locally advanced prostate cancer. A computer dealt each man apalutamide or placebo. The bottles were indistinguishable. The blind held from first pill to final scan, through surgery and five more years of follow-up. Treatment ran six 28-day cycles before the operation and six after. Surgeons removed the prostate along with nearby lymph nodes, and pathologists graded how much cancer was left in what came out. Spread was tracked afterward with bone scans, CT and newer PSMA-PET imaging.

Less Cancer at Surgery, Less Spread After It

Both of the trial’s main questions came back positive. At the operating table, 8.9% of men on apalutamide had no detectable cancer or only a trace left in the removed prostate, versus 1.0% on placebo.¹ Over a median of about five years, the risk of spread or death was 20% lower (hazard ratio 0.80, confidence interval 0.67 to 0.96). Men on the drug also went far longer before needing any further treatment: a median of 74.2 months versus 41.5, nearly three extra years. The investigators, whose trial was funded by the drug’s maker, called the combination a potential new standard of care for this group.

The Bill Comes Mostly as Rash

The added drug wasn’t free of cost to the body. Severe side effects hit 39.6% of the apalutamide group against 31.0% on placebo. Rash did most of that damage. It affected a third of treated men. About 7% stopped treatment because of side effects, versus under 3% on placebo. A year of intensified hormone blockade also brings its familiar companions: fatigue, hot flashes and loss of libido. For a man facing this surgery, the trade now has numbers on both sides.

Key Takeaways

• Apalutamide plus hormone therapy, taken six months before and six months after prostate removal, lowered the risk of metastasis or death by 20% in high-risk disease; 78.2% versus 73.5% were spread-free at five years.
• Men on the drug were about nine times more likely to have little or no cancer left at surgery, and went nearly three years longer before needing further treatment.
• Severe side effects were more common with apalutamide, mostly rash, and about 7% of men stopped because of them.
• The trial was double-blind, placebo-controlled and ran at a median follow-up of about five years; it was funded by the drug’s manufacturer.

References

1. Taplin ME, Gleave M, Shore ND, et al. Perioperative Apalutamide in High-Risk Localized Prostate Cancer. The New England Journal of Medicine. 2026;DOI 10.1056/NEJMoa2603878. link