Utility of the Oncotype DX® Prostate Cancer Assay in Clinical Practice for Treatment Selection in Men Newly Diagnosed with Prostate Cancer: A Retrospective Chart Review Analysis

122 Background: With evidence showing over treatment, more patients are choosing active surveillance (AS) for intermediate or lower risk prostate cancer (CaP). Genomic profiling is offered to risk stratify patients to aid in management decision−making. This study reports risk discrepancies between National Comprehensive Cancer Network (NCCN) criteria and OncotypeDx Genomic Prostate Score (GPS) and how this influences decision−making in our CaP population. Methods: An inception cohort study was carried out on 56 patients with NCCN very low to intermediate risk CaP who were candidates for AS and underwent GPS testing on prostate biopsy specimens performed within 6mo of entry. GPS provided a score corresponding to a GPS-based risk stratification. Study endpoints: 1) distribution of GPS risk groups within each NCCN risk category; 2) frequency of change to lower or higher risk based on GPS; 3) effect of GPS on physician recommendations and patient choice on disease management. Results: 52/56 patients had sufficient carcinoma on biopsy for a GPS analysis. GPS reassigned risk in 23% (12/52) of patients, with 10 going from NCCN low risk to GPS very low risk and 2 assigned to a higher GPS risk profile (Table). AS was recommended in 19 patients with GPS very low risk group and 8 patients in the GPS-defined low risk group. Physicians recommended treatment to 7 patients with GPS intermediate risk. Patient choice was congruent with physician recommendation in all cases. No patients chose AS when assigned to a higher risk category. All 10 patients reassigned to a lower risk category chose AS. Conclusions: In this CaP cohort, assessment by GPS changed risk stratification in 23% of patients. Moving to a different risk category changed physician recommendation and patient choice in the corresponding direction (to surveillance or therapy) in all cases. More study and larger sample size are needed to fully assess the effect of GPS on clinical decision making. [Table: see text]

A recent surge in biomarkers to aid management of men with prostate cancer has occurred. Their applications are varied and not all tests are applicable to the active surveillance setting. To review primary evidence on genetic and immunohistochemical biomarkers, and their role on patient selection and risk stratification for men on active surveillance for prostate cancer. A PubMed electronic search using the terms (biomarker or genetic or histopathological) AND ("prostate cancer" AND "active surveillance") was performed from inception to April 2015. Of the biomarkers reviewed, Prostate Health Index (PHI) and Oncotype DX Genomic Prostate Score (GPS), were identified to currently hold greatest potential benefit to aid risk stratification of men for AS. Higher PHI, at baseline and during follow-up, was shown to predict pathological upgrading at rebiopsy at two single institutions, but with small cohorts (n<200). The Oncotype DX GPS test has been validated on men suitable for AS but having upfront radical prostatectomy. Increase in GPS was shown to predict upgrading and upstaging at radical prostatectomy and biochemical recurrence post radical prostatectomy. Prospective validation in AS cohorts is yet to be performed. PHI and Oncotype DX GPS show promise in aiding risk stratification for men on AS. However, larger prospective studies in AS cohorts are needed. Integration of biomarkers with existing clinical and imaging models remains a challenge.

Objective: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) biopsy-based gene expression assay as a predictor of adverse pathology (AP: Pathologic Gleason score ≥4+3, presence of any Gleason 5, and/or ≥pT3) in African American (AA) men. Methods: Between February 2009 and September 2014, AA and European American (EA) men with very low, low, and intermediate risk prostate cancer (PCa) enrolled in a multi-institutional prospective study of vitamin D impacts of biopsy outcomes. The subset who proceeded to immediate radical prostatectomy (RP) after biopsy with available biopsy tumor blocks was included in a comparative effectiveness analysis of GPS on biopsy and its association with surgical AP on RP using logistic regression and receiver operating characteristic curves. Multiplicative interactions tested for differential prediction of GPS accuracy by race (AA vs. EA). Results: Overall, 102 AA and 76 EA men elected RP, out of which 51 (47.2%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units] in AA: 4.78; 95% CI 1.8-12.5, P =0.001; and EA: 4.41; 95% CI 1.6-11.9, P =0.003) in univariable analysis. On multivariate analysis, there was a significant interaction between GPS and race (P=0.01). On race stratified binary logistic regression, AP remained significant after adjustment for NCCN risk group in both AA and EA men (OR/20 units in AA: 3.29; 95% CI 1.2-9.1, P =0.02; and EA: 4.24; 95% CI 1.4-12.6, P =0.01). Area under the curves for AP using GPS/20 units was 0.719 for AAs vs. 0.745 for EAs (P=0.39). Conclusion: In this AA validation study, the Oncotype Dx PCa assay was confirmed as an independent predictor of AP at prostatectomy in AA and EA men with similar predictive accuracy, though there was evidence of effect modification by race. Citation Format: Samuel Carbunaru, Virgilia Marcias, Peter Gann, Roohollah Sharifi, Ximing Yang, Michael Dixon, Chase Gorbein, Borko Jovanovic, Andre Kajdacsy-Balla, Adam B. Murphy. Oncotype DX assay has similar predictive accuracy for adverse pathology at radical prostatectomy in African American and European American men [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A067.

97 Background: The OncotypeDX Genomic Prostate Score (GPS) test is a RNA expression assay that can be performed on needle-core biopsies from men with prostate cancer (PCa). GPS has previously been validated as a predictor of adverse pathology in men with low-risk prostate cancer who undergo primary radical prostatectomy (RP). We sought to determine whether GPS was associated with increased risk of adverse pathology for men enrolled on active surveillance (AS) who undergo delayed RP. Methods: Of 1,662 men enrolled on AS at the University of California San Francisco (UCSF) who consented for prospective data collection, we evaluated 215 men on AS with Gleason score (GS) 3+3 and GS 3+4 PCa who underwent GPS testing at diagnostic or confirmatory biopsy (ie. within 1 year). Patients had at least 6 biopsy cores sampled and ≤ 33% positive cores, stage T1 or T2 disease, PSA &lt; 20, and clinical Cancer of the Prostate Risk Assessment (CAPRA) score &lt; 6. The primary outcome was adverse pathology at delayed RP, defined as GS ≥ 4+3, stage ≥ pT3a or pN1. We performed Cox proportional hazards regression, and inverse probability censored weights (IPCW) models to evaluate association between GPS and adverse pathology, adjusting for CAPRA score. Results: 72 percent (N=154) of the cohort had GS 3+3, and 28 percent (N=61) had GS 3+4. 83 percent of men (N=179) were low risk, and 17 percent of men (N=36) were intermediate risk by CAPRA scoring. Median GPS was 26.4 (interquartile range [IQR]: 18.8, 34.6). Median time from diagnosis to RP was 23 months (IQR: 15, 40). 121 men had adverse pathology on delayed RP at a median time of 27 months (IQR 16, 43) to prostatectomy. In a Cox-proportional hazards regression adjusted for CAPRA, GPS was associated with increased risk of adverse pathology at delayed RP (Hazard Ratio [HR] per 5 units: 1.12, 95 Confidence Interval [CI]: 1.05, 1.20, p &lt; 0.01). CAPRA score was not associated with adverse pathology (p=0.09). IPCW model findings were very similar to Cox results. Conclusions: In patients who undergo RP after a relatively short period of AS, a higher GPS is associated with increased risk for adverse pathology on delayed RP.

The Oncotype Dx Genomic Prostate Score (GPS) is a 17-gene relative expression assay that predicts adverse pathology at prostatectomy. We conducted a novel randomized controlled trial to assess the impact of GPS on urologist's treatment preference for favorable risk prostate cancer (PCa): active surveillance versus active treatment (i.e., prostatectomy/radiation). This is a secondary endpoint from the ENACT trial which recruited from three Chicago hospitals from 2016 to 2019. Ten urologists along with men with very low to favorable-intermediate risk PCa were included in the study. Participants were randomly assigned to standardized counseling with or without GPS assay. The main outcome was urologists' preference for active treatment at Visit 2 by study arm (GPS versus Control). Multivariable best-fit binary logistic regressions were constructed to identify factors independently associated with urologists' treatment preference. Two hundred men (70% Black) were randomly assigned to either the Control (96) or GPS arm (104). At Visit 2, urologists' preference for prostatectomy/radiation almost doubled in the GPS arm to 29.3% (29) compared to 14.1% (13) in the Control arm (p = 0.01). Randomization to the GPS arm, intermediate NCCN risk level, and lower patient health literacy were predictors for urologists' preference for active treatment. Limitations included sample size and number of urologists. In this study, we found that GPS testing reduced urologists' likelihood to prefer active surveillance. These findings demonstrate how obtaining prognostic biomarkers that predict negative outcomes before treatment decision-making might influence urologists' preference for recommending aggressive therapy in men eligible for active surveillance.

A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men

Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer

Integrating the Genomic Prostate Score into Clinical Practice Workflow

124 Background: A biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) providing a Genomic Prostate Score (GPS) as a measure of tumor aggressiveness has been validated as a predictor of adverse pathologic and oncologic outcomes. We sought to evaluate the change in GPS results among men with favorable-risk prostate cancer (PCa) managed with active surveillance (AS). Methods: We identified men with low and intermediate-clinical risk PCa managed with AS at our institution receiving a minimum of two GPS tests on serial prostate biopsy. GPS ranges from 0 (least) to 100 (most aggressive disease). We described the change in assay results and clinical risk designation over time and reported the subsequent clinical outcome (definitive treatment versus continued AS). For men receiving treatment with radical prostatectomy (RP) the occurrence of adverse pathological findings was defined by the presence of high grade (Gleason pattern ≥ 4+3) or non-organ confined disease ( ≥ pT3a). Results: 31 men were identified who underwent serial GPS testing at a median of 12 months. The median change in GPS was an increase of 1 point (IQR -7, 13). Fourteen (45%) patients experienced an increase in NCCN risk classification, including 3 from very-low to intermediate and 11 from low to intermediate risk. Following serial GPS testing 7 patients (23%) underwent radical prostatectomy. Among surgically treated patients, 3 had adverse pathology due to pT3a disease and the mean change in GPS prior to treatment was an increase of 13 points (IQR -7, 18); all of whom were intermediate clinical risk at the time of surgery. This study was limited by the small sample size and the uncontrolled decision to pursue definitive therapy. Conclusions: Serial change in a tissue based gene expression assay on serial biopsy during AS was non-static. Magnitude of GPS change may identify men at risk for adverse pathological findings, although larger series are required to validate such an endpoint during AS.

A 17-Gene Genomic Prostate Score as a Predictor of Adverse Pathology in Men on Active Surveillance.

Correlation of a Commercial Genomic Risk Classifier with Histological Patterns in Prostate Cancer

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

Tissue-based genomic classifiers (GCs) have been developed to improve prostate cancer (PCa) risk assessment and treatment recommendations. To summarize the impact of the Decipher, Oncotype DX Genomic Prostate Score (GPS), and Prolaris GCs on risk stratification and patient-clinician decisions on treatment choice among patients with localized PCa considering first-line treatment. MEDLINE, EMBASE, and Web of Science published from January 2010 to August 2024. Two investigators independently identified studies on risk classification and treatment choice after GC testing for patients with localized PCa considering first-line treatment. Relevant data extracted by 1 researcher and overread by a second. Risk of bias (ROB) was assessed in duplicate. Ten studies reported risk reclassification after GC testing. In low ROB observational studies, very low- or low-risk patients with PCa were more likely to have their risk levels classified as the same or lower (GPS, 100% to 88.1%; Decipher, 87.2% to 82.9%; Prolaris, 76.9%). However, 1 randomized trial found that GC testing with GPS reclassified 34.5% of very low-risk and 29.4% of low-risk patients to a higher risk category. Twelve observational studies indicated that treatment decisions after GC testing either remained unchanged or slightly favored active surveillance. In contrast, analyses from a single randomized trial found fewer choices for active surveillance after GPS testing. Heterogeneity in screening patterns, risk-determination cutoffs, pathology, and clinical practices. Studies on treatment choice were moderate to high ROB. Although GC tests do not consistently influence risk classification or treatment decisions, the differences observed between observational and randomized studies highlight a need for well-designed trials to explore the role of GC tests in patients with newly diagnosed PCa considering first-line treatment. U.S. Department of Veterans Affairs. (PROSPERO: CRD42022347950).

A 17-gene Panel for Prediction of Adverse Prostate Cancer Pathologic Features: Prospective Clinical Validation and Utility

Prospective Correlation between Likelihood of Favorable Pathology on the 17-Gene Genomic Prostate Score and Actual Pathological Outcomes at Radical Prostatectomy