New Study Finds Hormone Combination Therapy Improves Survival in Recurrent Prostate Cancer

A New Approach for Men Whose Cancer Returns

Prostate cancer is one of the most common cancers among men. Many patients respond well to initial treatments like surgery or radiation, but some later experience a rise in prostate-specific antigen (PSA) levels which is an early sign that the cancer may be coming back.

A new study published in The New England Journal of Medicine offers promising news. Researchers found that using two hormone-based medicines together.  These two meds were  enzalutamide and leuprolide which helped men with recurrent prostate cancer live longer and delayed the cancer’s return compared to standard therapy alone.

Why Researchers Studied This Combination

Prostate cancer cells grow in response to male hormones called androgens, such as testosterone. Treatments known as androgen-deprivation therapies (ADT) lower or block these hormones.

Leuprolide lowers testosterone levels in the body, while enzalutamide blocks the hormone’s ability to attach to and fuel cancer cells. By combining the two, researchers hoped to better stop the cancer from growing and spreading.

This study focused on men with biochemically recurrent prostate cancer — meaning their PSA levels were increasing after surgery or radiation, even though scans didn’t yet show visible tumors. These men are considered high risk for developing advanced disease.

What Did the Research Discover?

The EMBARK trial was a phase 3 clinical study involving 1,068 men with high-risk, recurrent prostate cancer. Participants were randomly assigned to one of three treatment groups:

• Enzalutamide plus leuprolide
  
• Leuprolide alone (the standard treatment)
  
• Enzalutamide alone (monotherapy)
  

Men were followed for almost eight years to measure survival and disease progression.

Key Results:

• The 8-year overall survival rate was 78.9% for men taking both drugs, compared with 69.5% for those taking leuprolide alone.
  
• This means the risk of death was about 40% lower with combination therapy.
  
• Men on the combination also went longer before needing more treatment or seeing their cancer spread.
  
• The enzalutamide-only group had a survival rate of 73.1%, which was slightly higher than leuprolide alone but not significantly better.
  
• Common side effects included hot flashes, fatigue, and breast tenderness, while serious side effects such as high blood pressure or falls were less common. About 27% of men stopped treatment due to side effects.
  

How Can I Apply This Information?

This study shows that combining enzalutamide and leuprolide may help men with recurrent prostate cancer live longer and delay disease progression.

It’s important to remember that this is research and not yet a new combination drug approval. However, doctors often use results of research to know which combinations to use and these results provide evidence that earlier and more complete hormone control can improve survival in men with rising PSA levels after initial treatment.

Patients should discuss the potential benefits and side effects with their doctor, as hormone therapy can cause fatigue, mood changes, and sexual side effects. With careful monitoring, however, many side effects can be managed successfully.

This study adds to growing evidence that stronger combination hormone therapy may offer men with recurrent prostate cancer more time and better quality of life.

Source:

Smith MR, Higano CS, Shore ND, et al. Enzalutamide in combination with leuprolide and as monotherapy in men with biochemically recurrent prostate cancer (EMBARK): a phase 3, randomized trial. N Engl J Med. 2025;392(5):403–415. doi:10.1056/NEJMoa2510310. Accessed by: https://www.nejm.org/doi/full/10.1056/NEJMoa2510310