Novel Genomic Test Predicts Which Patients Benefit from Hormone Therapy Plus Radiation in Recurrent Prostate Cancer

A randomized clinical trial has validated the first genomic test that can predict which men with recurrent prostate cancer benefit from adding hormone therapy to radiation after surgery. The findings, from the phase II BALANCE trial (NRG Oncology GU006), were presented today at the 2025 ASTRO Annual Meeting.

“We’ve been searching for decades for a way to determine which patients are most likely to respond to hormone therapy after prostatectomy,” said Daniel Spratt, MD, principal investigator and professor of radiation oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University. “We now have a tool that lets us tailor treatment based on a tumor’s biology and recommend hormone therapy only for those patients who we think can expect to see a benefit.”

Hormone therapy is often added to radiation to block testosterone, which fuels prostate cancer growth. While it can improve outcomes, it also causes side effects such as fatigue, bone loss, hot flashes, and cardiovascular risks. Until now, doctors lacked a reliable way to determine who truly benefits.

The new approach uses PAM50, a gene expression test originally designed for breast cancer, adapted to classify prostate tumors. In the study, tumors were grouped as luminal B (fast-growing, more hormone-sensitive) or non-luminal B.

Among the 295 patients enrolled, those with luminal B tumors saw striking benefits from adding the hormone therapy apalutamide to radiation:

• Five-year progression-free survival: 72.4% with apalutamide vs. 53.9% with placebo (p=0.0062)
• Five-year metastasis-free survival: 94.7% vs. 81.8% (p=0.029)

Patients without luminal B tumors, however, gained no benefit. Their outcomes were nearly identical whether or not they received hormone therapy.

“The patients with luminal B tumors saw a large benefit, both in reducing recurrence and lowering the risk of metastatic disease,” Dr. Spratt said. “But for patients without this subtype, hormone therapy didn’t change the outcome. That’s incredibly valuable information when we’re trying to personalize care.”

Dr. Spratt said the results are likely to change practice. “This is the first prospectively validated predictive biomarker in prostate cancer. 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.”

Because the results were so definitive, researchers said a larger phase III trial is unlikely. PAM50, already available in breast cancer care, could soon be used in prostate cancer to guide treatment decisions.