The first prospective validation trial for a predictive biomarker in non-metastatic prostate cancer has demonstrated that the PAM50 molecular signature can identify which patients with recurrent disease will benefit from hormone therapy. Results from the randomized BALANCE trial, presented at ASTRO 2025, show significant treatment response differences based on molecular subtype classification.
Trial Design and Patient Population
The BALANCE trial (NCT03371719) enrolled 295 men with recurrent, non-metastatic prostate cancer following prostate-removal surgery. Patients were randomly assigned to receive salvage radiation therapy with either placebo or apalutamide for 6 months. The PAM50 biomarker served as a key stratification variable to ensure balanced distribution of luminal B and non-luminal B subtypes across treatment arms.
Participants were followed for a median of 5 years and evaluated for biochemical failure, defined as a rise in prostate-specific antigen (PSA) levels post-treatment—an early indicator of salvage therapy failure.
Molecular Subtype Determines Treatment Response
The trial revealed striking differences in treatment response based on PAM50-defined molecular subtypes. Among the 127 men with luminal B molecular subtype tumors, 72% of those receiving apalutamide did not experience biochemical failure, compared to 54% in the placebo group [HR 0.45 (80% CI 0.29-0.68), p=0.0062].
In contrast, patients with non-luminal B subtypes showed no difference between apalutamide and placebo treatment, with 70% versus 71% avoiding biochemical failure respectively [HR 0.95 (80% CI 0.65-1.41), p=0.44].
"Our findings mark the first time, to my knowledge, that a predictive biomarker has been validated in a prospective, biomarker-driven, randomized trial in non-metastatic prostate cancer," said Daniel Spratt, M.D., from University Hospitals Seidman Cancer Center, Case Western Reserve University, who presented the findings.
Clinical Implications for Personalized Treatment
The results provide the highest level of evidence supporting routine biomarker testing in recurrent prostate cancer patients planned for secondary radiotherapy. Dr. Spratt emphasized the clinical significance: "With such a strong difference in the metastasis-free survival response to hormone therapy between luminal B and non-luminal-B tumors, the use of the predictive PAM50 biomarker is a game changer to help personalize treatment for men with recurrent prostate cancer beyond merely prognostic tools."
This advancement allows for more precise patient selection, enabling clinicians to identify those who will benefit from hormone therapy while sparing others from unnecessary treatment and potential side effects.
Expanding Biomarker Applications
The PAM50 signature represents the third biomarker assessed through Veracyte's whole-transcriptome-based Decipher platform that has demonstrated predictive value for hormone therapy, radiation therapy, or chemotherapy benefit in major studies. Another ongoing trial, PREDICT-RT, completed enrollment two years early and is evaluating the Decipher Prostate test's ability to predict benefit from combined hormone therapy concurrent with radiation in high-risk prostate cancer patients at initial diagnosis.
"Prostate cancer, like all cancers, is a disease of the genome," said Elai Davicioni, Ph.D., Veracyte's medical director for Urology. "Our Decipher GRID tool uniquely enables researchers to better pinpoint adverse molecular features that are associated with poor outcomes. This can ultimately lead to more-personalized care for each patient based on their tumor's unique molecular make-up."
The prostate PAM50 biomarker is currently available for Research Use Only on the Decipher GRID research tool, with the BALANCE trial results representing one of nine Decipher-focused abstracts presented at ASTRO 2025.
