Innovative Genomic Test Guides Personalized Hormone Therapy in Recurrent Prostate Cancer

A groundbreaking clinical study has introduced a novel genomic testing method that helps determine which patients with recurrent prostate cancer will benefit most from adding hormone therapy to radiation after surgery. This is the first time a molecular biomarker has been validated to predict treatment responsiveness in this setting.

The study focused on a gene expression test called PAM50, originally developed for breast cancer, and adapted to evaluate prostate tumor biology. Researchers found that patients with a specific tumor subtype known as luminal B experienced significantly lower risks of cancer recurrence and metastasis when treated with radiation combined with apalutamide, a second-generation antiandrogen hormone therapy. Conversely, patients with non-luminal B tumors showed no advantage from additional hormone therapy.

This phase II trial, named BALANCE (NRG Oncology GU006), enrolled 295 men who had undergone prostatectomy and were experiencing rising PSA levels but showed no distant metastasis. Participants were randomized to receive standard radiation therapy with either six months of apalutamide or placebo. Tumors were classified into luminal B or non-luminal B types through the PAM50 test. After a median follow-up of five years, luminal B patients receiving hormone therapy demonstrated a notable improvement in two critical outcomes: biochemical progression-free survival (72.4% versus 53.9%) and metastasis-free survival (94.7% versus 81.8%). In contrast, non-luminal B patients showed no difference in these outcomes regardless of treatment.

Dr. Daniel Spratt, the principal investigator, emphasized the significance of these findings, stating, "This is the first prospectively validated biomarker for treatment personalization in prostate cancer. It enables us to tailor therapy, offering hormone treatment only to those likely to benefit, thereby minimizing unnecessary side effects."

Prostate cancer remains the second most common cancer worldwide, with over 314,000 new cases expected in the U.S. this year. Despite effective initial treatments such as radiation and surgery, up to 30% of patients experience disease recurrence signaled by rising PSA levels. Hormone therapy helps inhibit testosterone, which fuels tumor growth, but it also causes side effects like fatigue, bone loss, hot flashes, and cardiovascular risks. The ability to identify patients who will respond to hormone therapy marks a significant step forward in personalized cancer care.

The development of the PAM50 test in prostate cancer was led by Dr. Spratt and colleagues, who adapted a tool originally used for breast cancer. Tumors classified as luminal B tend to grow rapidly but are highly hormone-responsive, making hormone therapies effective. Non-luminal B tumors, such as luminal A and basal-like types, are less dependent on testosterone, explaining the lack of benefit from added hormone therapy in these cases.

The study's results suggest that incorporating this genomic test into clinical practice could revolutionize treatment decision-making, reducing unnecessary hormone therapy use and its associated side effects while improving outcomes for patients with the luminal B subtype. Dr. Spratt predicts that, given the compelling data, further phase III trials are unlikely, and PAM50-guided decision-making may become a new standard in managing recurrent prostate cancer.

Source: https://medicalxpress.com/news/2025-09-kind-genomic-benefit-hormone-therapy.html