How a Veterans Affairs Study Can Help Guide Prostate Cancer Treatment

A nationwide Veterans Affairs (VA) study comparing two leading treatments for metastatic prostate cancer may help doctors choose the right drug for each patient, said a Rutgers Cancer Institute physician-scientist whose invited editorial accompanies the research.

In the editorial published alongside the study in JCO Clinical Cancer Informatics, Wadih Arap, chief of oncology/hematology at Rutgers New Jersey Medical School, said the findings provide some of the strongest real-world evidence to date comparing enzalutamide with abiraterone, two commonly prescribed hormone therapies for metastatic castration-sensitive prostate cancer. 

While the study found that the drugs produced similar outcomes overall, enzalutamide may offer a modest survival advantage for patients aged 75 and older.

“For years, physicians have largely relied on their own historical precedent rather than direct empiric evidence when deciding which of these therapies to prescribe first,” said Arap, who also directs the cancer program at University Hospital, an outpost of Rutgers Cancer Institute, New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, together with RWJBarnabas Health. 

“Large studies like this give clinicians better information to individualize treatment based on the patient sitting in front of them,” he added.

Hormone therapy has been the cornerstone of treating prostate cancer that has spread from its original site for many decades. The disease initially depends on testosterone (the main male hormone) to grow, making therapies that block or suppress the hormone highly effective. Although enzalutamide and abiraterone both reduce the cancer’s ability to use testosterone, they do so in different ways. Until now, only one publication—another VA study, but with fewer patients--had retrospectively compared the two drugs in prostate cancer patients in the metastatic castration-sensitive setting.

Researchers involved in the new study analyzed records of 5,135 veterans treated throughout the VA health system between 2020 and 2023. They found that patients receiving either drug experienced similar overall survival, time to treatment change and prostate cancer-specific survival. Among patients 75 and older, however, those receiving enzalutamide lived modestly longer than those treated with abiraterone.

Arap noted that the gap is small but worth acting on – and that it might perhaps stem less from cancer drugs themselves than from the usually required co-administration of steroids with abiraterone.

Abiraterone blocks the enzyme that builds testosterone, which also suppresses the body’s production of cortisol. Patients take a low daily dose of prednisone to compensate, and in men who already have heart disease or diabetes, years of steroid exposure carry additional risk. 

Enzalutamide, which keeps testosterone from reaching the tumor rather than stopping its production, requires no co-administration of steroids.

In the editorial, Arap argues the study also highlights the value of the VA’s integrated health system as a research resource. Because the VA has maintained decades of unified electronic medical records in an otherwise fragmented U.S. health care system, it offers researchers a unique opportunity to conduct large-scale studies such as this.

“The VA is one of the closest things the United States has to the national health care databases used for large population studies in countries like the U.K. or Sweden, Norway and Denmark,” Arap said. “That makes it possible to answer important clinical cancer management questions by using real-world data at a population scale that’s hard to achieve elsewhere.”

Arap said the findings may be particularly useful when treating older patients or those with other medical conditions that can influence how well they tolerate therapy. Rather than pointing to a single best treatment for every patient, he said, the study gives physicians additional evidence to match therapy to an individual’s age, health and preferences.

The editorial concludes that additional research is needed to confirm whether older patients consistently benefit more from enzalutamide. Still, Arap said studies such as this demonstrate how carefully analyzed real-world clinical data can answer practical questions that conventional clinical trials have left unresolved.