Introduction:

Clinicopathologic features, such as Prostate Specific Antigen (PSA) and Gleason Score have been considered the gold standard for predicting disease severity and for guiding decision-making to pursue Active Surveillance (AS) or definitive treatment (DT). Prolaris is a commercially available test that combines a molecular score with clinicopathologic features to produce a Combined Clinical Risk (CCR) score; this score can be used to predict the likelihood of disease specific mortality and metastasis. This test has been clinically validated in untreated patients across all National Comprehensive Cancer Network (NCCN)-risk groups, and clinical utility studies in different risk groups are ongoing. The purpose of this prospective study was to evaluate the clinical utility of Prolaris to guide medical decisions on the selection and durability of AS in patients with NCCN Intermediate-risk prostate cancer.

Methods:

Patients were tested with Prolaris between 09/2015-12/2018, following diagnosis with NCCN favorable- or unfavorable-intermediate risk prostate cancer at 10 community or academic urology clinics. CCR scores were calculated based on UCSF Cancer of the Prostate Risk Assessment (CAPRA) score and molecular variables identified from the sample submitted for testing. Patients with CCR-based 10-year disease specific mortality risk of ≤3.2% were considered below the AS threshold. Clinical follow-up data were reported by the clinics. Patients were required to have at least six months of follow-up to establish AS selection, which was defined as six or more months without DT following diagnosis. For patients who initially selected AS, AS durability was defined as the time from diagnosis to first DT. Logistic regression was used to predict binary AS selection. Cox proportional hazards models and Kaplan-Meier methods were used to describe AS durability at three years post-diagnosis.

Results:

The analysis set consisted of 3138 patients (56% favorable-intermediate, 44% unfavorable-intermediate), 1439/3138 (46%) of whom had CCR-based mortality risks below the AS threshold. Patients with CCR-based mortality risk above the AS threshold were significantly less likely to initially select AS (20.4%, 95% confidence interval (CI) 18.5%-22.4%) than patients with risk below the threshold (42.2%, 95% CI 39.6%-44.8%; OR 0.41, 95% CI 0.36-0.47, p<0.001).  In a bivariable model predicting initial AS vs DT selection, AS threshold status added significant, predictive information over CAPRA alone (AS threshold status OR 0.57, 95% CI 0.50-0.65, p<0.001). Patients with CCR-based mortality risk below the AS threshold were also more likely to stay on AS longer than patients with risk above the threshold (HR 1.68, 95% CI 1.38-2.03, p<0.001). The three-year AS durability rate was 52.5% (95% CI 48.0%-56.8%) for patients below the AS threshold, and 33.2% (95% CI 27.6%-38.9%) for patients above the threshold.

Conclusion:

In this study, the largest to date to assess the clinical utility of the AS threshold in NCCN intermediate risk men, patients with CCR-based mortality risk below the AS threshold were more likely to initially select AS compared to patients with scores above the threshold. Additionally, patients with CCR-based mortality risk below the AS threshold experienced higher durability of AS. Together, these findings demonstrate that Prolaris provides important clinical information that significantly impacts treatment decisions in patients with NCCN favorable- and unfavorable-intermediate risk prostate cancer.    

Funding: Myriad Genetics, Inc.