The phase 3 PREDICT-RT trial (NRG-GU009; NCT04513717) has successfully completed enrollment with 2,478 adult patients across clinical trial sites in the United States and Canada, marking a significant milestone in precision oncology for high-risk prostate cancer. The study evaluates a novel risk stratification approach using genomic testing to assign patients to either de-intensified or intensified concurrent hormone therapy and radiation regimens.
Genomic-Guided Treatment Assignment
The trial utilizes Decipher genomic testing to determine treatment intensity based on individual tumor biology. Patients with a low Decipher risk score (≤0.85) are assigned to the de-intensification study, while those with high Decipher scores (>0.85) or node-positive disease enter the intensification arm.
"The incidence of men receiving high-risk prostate cancer diagnoses is on the increase in recent years," explained principal investigator Paul L. Nguyen, MD, MBA, of Mass General Brigham and Dana Farber Cancer Centers. "The PREDICT-RT study was designed to improve quality of life and outcomes for these patients while tailoring treatments to meet each individual's needs based on their Decipher Prostate Genomic Classifier scores, which use the tumor's genomic information to predict aggressiveness."
De-intensification Strategy for Low-Risk Genomic Profiles
In the de-intensification study, participants are randomly assigned to receive either standard radiotherapy with 24 months of androgen deprivation therapy (ADT) or radiotherapy with a shortened 12-month ADT duration. This approach aims to determine whether patients with high-risk prostate cancer but favorable genomic profiles can achieve non-inferior metastasis-free survival with reduced treatment intensity, potentially minimizing long-term side effects.
Patients in this arm are stratified by Decipher score range, boost type, prior pelvic treatment, and ACE-27 comorbidity status to ensure balanced randomization across clinically relevant subgroups.
Intensification Approach for High-Risk Genomic Signatures
The intensification study randomizes patients to receive either standard radiotherapy with 24 months of ADT or the same regimen plus 24 months of apalutamide (Erleada). The primary objective is to determine whether adding the next-generation androgen receptor inhibitor can improve metastasis-free survival in patients with high-risk prostate cancer and elevated Decipher scores.
Stratification factors for this cohort include boost type, prior pelvic treatment, and nodal status, reflecting the more advanced disease characteristics in this population.
Comprehensive Endpoint Assessment
The primary endpoint for both studies is metastasis-free survival, with co-primary endpoints encompassing patient-reported quality of life measures. Secondary objectives include overall survival, prostate cancer-specific survival, prostate-specific antigen failure-free survival, time to testosterone recovery, and safety assessments.
The study design reflects growing recognition that treatment decisions should incorporate both clinical risk factors and tumor biology to optimize outcomes while minimizing treatment-related morbidity.
Long-term Follow-up and Expected Impact
Patients will be followed for up to 13 years, with final trial completion expected in December 2033. This extended follow-up period will provide robust long-term efficacy and safety data to inform clinical practice guidelines.
"Our study team would like to thank our sites and our patients who quickly enrolled to this very important trial," concluded co-principal investigator Oliver Sartor, MD, of East Jefferson General Hospital Cancer Center. "We look forward to reporting the results as data becomes available from this trial."
The successful completion of enrollment demonstrates strong clinical interest in genomic-guided treatment approaches and positions the trial to provide definitive evidence for personalized prostate cancer management strategies.
