A recent study presented at the 2024 Society of Urologic Oncology (SUO) annual meeting in Dallas, TX, demonstrates that the Decipher® Genomic Classifier (GC) score on index biopsy is an independent predictor of clinical progression in prostate cancer patients undergoing active surveillance, irrespective of initial MRI results.
Need for Improved Risk Stratification
Active surveillance is a widely endorsed strategy for managing low- and very low-risk prostate cancer, aiming to minimize overtreatment morbidity. However, progression to definitive therapy occurs in 20% to 50% of patients within five years of active surveillance initiation, underscoring the need for improved early risk stratification. Clinical tools like multiparametric magnetic resonance imaging (mpMRI) and Decipher® GC are recommended for risk stratification, but longitudinal evidence supporting tissue biomarker testing, independent of mpMRI, has been limited.
Study Design and Objectives
The study aimed to evaluate the associations between imaging (mpMRI) and genomic (Decipher® GC) risk stratification scores at prostate cancer diagnosis with the rate of progression to definitive therapy in active surveillance patients. A secondary objective was to determine if combining mpMRI imaging with genomic testing enhances predictive utility.
Researchers conducted a retrospective analysis of consecutive active surveillance patients from biopsies submitted for Decipher® GC testing between December 2016 and December 2023. They assessed variables such as serum prostate-specific antigen (PSA) level, index biopsy Gleason Grade Group, NCCN risk group, mpMRI Prostate Imaging-Reporting and Data System (PI-RADS) classification score, and Decipher® GC score. Treatment progression timing was also recorded. mpMRI findings were categorized as negative (PI-RADS 1–3) or positive (PI-RADS 4–5), and Decipher® scores were classified as low (<0.45), intermediate (0.45–0.6), or high (>0.6).
Key Findings
The study included 338 patients with a mean serum PSA level of 7.4 ng/ml. During a median follow-up of 26 months, 34% of patients progressed to definitive therapy. Independent evaluation of Decipher® GC score and mpMRI findings revealed that a Decipher® GC score ≥0.45 yielded a hazard ratio (HR) of 2.04 (95% CI: 1.39–2.99, p<0.001), while a PI-RADS 4-5 finding resulted in an HR of 1.85 (95% CI: 1.21–2.81, p=0.004) for treatment progression.
Decipher GC Score as an Independent Predictor
Given the weak correlation between genomic and imaging high-risk features (τb = 0.133, p=0.021), investigators evaluated the predictive utility of a Decipher® GC score ≥0.45, stratified by mpMRI PI-RADS findings. The Decipher® GC score ≥0.45 remained significantly predictive of treatment progression for all patients, including those with PI-RADS 4-5 disease (HR: 1.58, 95% CI: 0.99–2.5, p=0.05). However, a PI-RADS 4-5 lesion finding on mpMRI was not predictive of treatment progression in men with a Decipher® GC score ≥0.45.
Clinical Implications
Dr. Mark Sultan, MD, Resident Physician, Department of Urology, The Mayo Clinic, Jacksonville, FL, concluded that both elevated Decipher® GC scores (≥0.45) and mpMRI findings (PI-RADS 4-5 lesions) are associated with treatment progression following active surveillance initiation. The weak correlation between these tools suggests they capture distinct prognostic information and should be used in combination. The study validates the Decipher® GC score ≥0.45 as an independent predictor for progression to treatment for all active surveillance patients, irrespective of PI-RADS lesion classification, suggesting an individualized approach to active surveillance may be further enhanced using Decipher® GC testing, even for men with concerning mpMRI findings.
