SAN FRANCISCO — A genomic test can identify patients with recurrent prostate cancer who are most likely to benefit from adding hormone therapy to secondary radiotherapy, according to findings presented at the American Society for Radiation Oncology 2025 annual meeting.

Veracyte’s PAM50 molecular signature classifies prostate tumors as luminal B subtype or not. In the phase 2 BALANCE trial, adding apalutamide to standard radiotherapy improved the 5-year outcomes of men with biochemical recurrence following prostatectomy — but only if they had luminal B tumors.

“The patients with luminal B tumors saw a large benefit, both in reducing recurrence and lowering the risk of metastatic disease,” said principal investigator Daniel Spratt, MD, a prostate cancer radiation oncologist at Case Western Reserve University, Cleveland.

For patients without the luminal B subtype, hormone therapy had no impact on outcomes.

“This is the first prospectively validated predictive biomarker in prostate cancer,” Spratt said in an ASTRO press release. “It gives us a promising way to personalize care, recommending hormone therapy for those who respond, and avoiding unnecessary treatment when it is unlikely to help.” 

Chad Tan, MD, a genitourinary radiation oncologist at MD Anderson Cancer Center in Houston, called the findings a “win” for patients.

“As all my patients will tell you, no man likes hormone therapy,” Tan said. “The ability to help reduce that in a substantial subset of patients based on this biologic marker is a win for our patients.”

The PAM50 test was originally developed to help guide breast cancer treatment, and its utility in managing that disease led Spratt and his team to adapt it for potential use in prostate cancer. In a retrospective study, they discovered that prostate tumors classified as luminal B seemed to respond far better to hormone axis treatment than nonluminal B tumors.

For the BALANCE trial, the researchers enrolled 295 men with biochemical recurrence after prostatectomy and prostate-specific antigen levels no higher than 1 ng/mL; most had values below 0.5 ng/mL. Half of the patients had positive surgical margins, and about half had pathological T3 disease. None had evidence of metastatic disease.

PAM50 testing showed that that 43% of patients had luminal B tumors, while the rest had nonluminal B subtypes.

Patients were randomized to 6 months of either apalutamide or placebo in addition to secondary radiation. Apalutamide was chosen, Spratt said, because as an androgen receptor blocker, it doesn’t lower testosterone and avoids the associated side effects.

At 5 years follow up, patients with luminal B tumors had clearly benefited from the addition of hormone therapy. Their biochemical progression-free survival was 72.4% with apalutamide vs 53.9% with placebo (P = .0062). 

In contrast, apalutamide made no difference for patients with nonluminal B subtypes: biochemical progression-free survival was 70.2% with apalutamide vs 71.1% without it (P = .44). 

It was the same story with metastasis-free survival. Among patients with luminal B tumors, 5-year estimated metastasis-free survival was 94.7% with apalutamide vs 81.8% with placebo (P = .029). But among patients with other tumor subtypes, metastasis-free survival was nearly identical in both treatment arms: 89.9% with apalutamide and 89.3% with placebo (P = .90).

“It’s not often that prospective data confirms biologic data to this extent,” Tan said. “But in this case, it has, in a big way.”

Apalutamide treatment was associated with its known side effects, including self-limiting rash and hypertension; 5.7% of patients had grade 3 or higher gastrointestinal toxicity vs 2.6% of patients in the placebo arm.

As it stands, PAM50 results can be requested with Veracyte’s Decipher Prostate test, a commercially available gene expression assay that predicts recurrence risk. It’s a test, Spratt told Medscape Medical News, that he and his Case Western colleagues routinely order.

Until now, though, it hadn’t been clear how to use those PAM50 results. With the BALANCE findings in hand, Spratt said he will be using the test results in his practice.

“This is one of the largest benefits we've ever seen at the 5-year time point,” he said. 

The work was funded by the National Cancer Institute. Spratt and Tan have no commercial relationships with Veracyte.