TEST:

Decipher Prostate Cancer Test

Finally, this work explores the need for appropriately enriched investigational datasets and proper ground truth, and provides guidance on how to best conduct AI prostate MRI studies. Published in parallel, a clinical study applying this suggested study design was applied to review and report a multiple-reader multiple-case clinical study of 150 bi-parametric prostate MRI studies across nine readers, measuring physician performance both with and without the use of a recently FDA cleared Artificial Intelligence software.1.

P2; This analysis suggests that the Decipher genomic classifier may be prognostic for disease progression in AS patients with low- to intermediate-risk prostate cancer. Higher Decipher and AR-A scores, as well as PAM50 luminal subtypes, may also serve as biomarkers for treatment response.

P2 | N=227 | ENACT (NCT02799745) | Sponsor: Astellas Pharma Global Development, Inc.| "Veracyte, Inc...today announced that a new study published in JCO Precision Oncology shows that, among patients undergoing Active Surveillance (AS) for prostate cancer, the Decipher Prostate Genomic Classifier is prognostic for identifying those whose disease is likely to progress...The new findings are from the biomarker analysis study of the ENACT clinical trial (NCT02799745) that aimed to compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer....In the AS alone or control arm, among patients with available tumor samples (n=65), the Decipher Prostate test predicted increased rates of disease progression after adjusting for baseline clinical risk factors (MVA HR [95% CI] per 10% increase in score: 1.17 [1.01 to 1.35]; P = 0.04)."

"Veracyte, Inc...today announced that nine abstracts focused on its Decipher Prostate and Decipher Bladder Genomic Classifiers will be presented at AUA 2024, the annual meeting of the American Urological Association, taking place May 3-6 in San Antonio. Studies to be presented include those that evaluate the clinical utility of the company’s Decipher tests in guiding treatment decisions for patients with prostate or bladder cancer. Other presentations will explore new insights into these cancers’ underlying biology, which researchers derived through use of Veracyte’s whole-transcriptome-based Decipher GRID research tool."

Clusters of inflammatory cells in the RP specimen can be divided spatially into PT TLS and IT-TLS, each with its unique molecular correlates of tumor immune microenvironment. The presence of TLS is positively correlated with MHC signatures, T- cell and B-cell cluster signatures but, negatively correlated with immune suppressive signatures. A subset of prostate cancer demonstrate a robust inflammatory response, and warrant further characterization in larger cohorts.

P2, N=95, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Dec 2026 --> Dec 2027 | Initiation date: Mar 2024 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Dec 2026

Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.

Decipher® has been shown to independently predict adverse pathology in patients with very low-, low- and intermediate-risk PCa. We found that Decipher® and unfavorable intermediate risk biopsy are predictors of upgrading on prostatectomy, while mpMRI (PIRADS) and PSA are not. Decipher® Genomics Resource for Intelligent Discovery (GRID) is a transcriptomic database which providers over 46,000 gene expressions.

In a large scale, population-based, prospective assessment, we found wide variation in genomic risk distribution in clinical stage groups, suggesting integration of genomic and clinicopathologic risk groups may lead to more nuanced prediction of relevant clinical outcomes in PCa.

Using a large, diverse, national cohort, we observed considerable variations in gene expression profiles across groups by race, age, Gleason grade group, and geographic region that can address the genomic underpinnings of sociodemographic and geographic variation in prostate cancer outcomes.

Despite similar clinical features at diagnosis, AS-eligible patients have significantly different outcomes and risk of APF due to molecular heterogeneity. The Decipher genomic classifier, PTEN loss, and activated CD4 activity at diagnosis are associated with APF among AS eligible patients. Clinical trials within AS populations should consider utility of genomic signatures in patient selection.

Decipher Score appears to better predict distant metastases compared to PSA as the only high-risk feature among patients with Grade Group 1 or 2 disease after prostatectomy. Decipher may be a useful adjunctive tool when advising these patients on subsequent prognosis and management, as not all patients with PSA >20 are at high-risk for PCa metastases.

P2/3; N=493; Recruiting; Sponsor:Cancer Research Antwerp

"Veracyte...announced that its Decipher Prostate Genomic Classifier is the only gene expression test to receive a 'Level 1B' evidence rating in the 2024 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a prognostic tool for the risk stratification of patients with localized prostate cancer. Level 1B was assigned to Decipher Prostate based on the evidence in both the post-biopsy and post-prostatectomy settings. Additionally, because of this classification, the Decipher Prostate test is the only gene expression test for which the guidelines synthesize the available published data in a separate table that summarizes treatment implications for patients based on both their NCCN risk classification and Decipher score."

Risk group stratification of prostatic adenocarcinoma provided by information in the surgical pathology report on routine biopsy assessment coupled with serum PSA level is superior to Decipher testing for cases classified as genomic high-risk.

DL algorithms utilizing WSI with or without clinical-pathologic parameters outperform currently employed genomic classifiers for the prediction of metastasis. Validation in additional multi-institutional and racially diverse cohorts is underway.

P=N/A | N=900 | Recruiting | Sponsor: University of Michigan Rogel Cancer Center | Trial completion date: Nov 2023 ➔ Jul 2024 | Trial primary completion date: Nov 2023 ➔ Jul 2024

"Genomic classifiers provide a small but consistent improvement upon the prognostic ability of clinical classification schemes, which may be helpful when treatment decisions are uncertain. However, evidence from current management-era data and of the predictive ability of these tests is needed."

P2; Initiation date: Dec 2023 --> Mar 2024

We conclude that MD2 predicts metastatic behavior, and serum-MD2 could be studied as a potential non-invasive biomarker for metastasis, whereas MD2 presence on prostate biopsy predicts adverse disease outcome. We suggest MD2-targeted therapies could be developed as potential treatments for aggressive metastatic disease.

Despite similar clinical features at diagnosis, AS-eligible patients with similar clinical variables have significantly different outcomes and risk of APF due to molecular heterogeneity. Prognostic gene expression signatures such as the Decipher genomic classifier as well as PTEN loss and activated CD4 activity measured at diagnosis are associated with APF among AS eligible patients. Clinical trials within AS populations should consider utility of genomic signatures in patient selection.

"Veracyte...announced that new data presented today at the 24th Annual Meeting of the Society of Urologic Oncology (SUO 2023) highlight clinical observations and translational research conducted by users of the company’s Decipher Prostate Genomic Classifier. These independent, real-world studies provide further evidence supporting the clinical utility of the test in the treatment and management of prostate cancer, particularly for patients considering active surveillance."

"Veracyte, Inc...announced that seven posters will be presented at the 24th Annual Meeting of the Society of Urologic Oncology (SUO 2023), where they will demonstrate the clinical performance of Veracyte’s Decipher Prostate Genomic Classifier in identifying patients whose prostate cancer is likely to progress and require treatment. Collectively, the posters will report data from more than 60,000 patients. The meeting will take place in Washington, DC, from November 28 to December 1."

"Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management."

P2; N=90; Not yet recruiting; Sponsor:University of Kansas Medical Center

Our findings suggest that the Decipher score has a stronger correlation with grade progression than volume progression in prostate cancer patients. This highlights the potential of genomic classifiers like Decipher in enhancing our understanding of disease progression and in tailoring personalized treatment strategies. Further prospective studies are required to validate these findings.

Tumor-based molecular assays such as Decipher® GC are included in the NCCN guidelines for localized prostate cancer management. Decipher® GC has been shown to independently predict adverse pathology with ver low-, low- and intermediate-risk PCa. Previous studies have shown the association of Decipher® GC score with progression to treatment on AS without incorporating mpMRI data.

Tumor based molecular assays such as Decipher® GC are included in the NCCN guidelines for localized prostate cancer management. Decipher® GC has been shown to independently predict adverse pathology in patients with very low-, low- and intermediate-risk PCa. We found that Decipher® GCand unfavorable intermediate risk biopsy are predictors of upgrading on prostatectomy, while mpMRI (PIRADS) and PSA are not.

In a large scale, population-based, prospective assessment, we found wide variation in genomic risk distribution within and across clinical stage groups, suggesting integration of genomic and clinicopathologic risk groups may lead to more nuanced prediction of relevant clinical outcomes in PCa. These findings may help individualize risk assessment, yielding more precise prognosis estimates for patients.

P2; Trial completion date: Oct 2025 --> Dec 2026

The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.

"Veracyte...announced that new data from a large, randomized phase 3 trial reinforce the value of the Decipher Prostate Genomic Classifier in helping physicians make more informed treatment decisions for their patients with prostate cancer. The findings, presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting, suggest that the Decipher Prostate test can categorize more accurately risk of patients with clinically high-risk disease to help inform appropriate treatment."

P2; N=95; Not yet recruiting; Sponsor:Jonsson Comprehensive Cancer Center

P1 | "A majority of subjects demonstrate a post-SBRT increase in GC score with reclassification of genomic-prognostic risk group in 58%. An enrichment of the basal-immune molecular subtype was observed following SBRT suggesting a convergence towards this biology in irradiated tumors."

Higher Decipher scores were associated with distant metastasis on PSMA PET in both the de novo and recurrent setting. Transcriptomic differences in pathways related to proliferation, p53 status, and PAM50 classification were seen when comparing localized, node-positive, and distant metastatic disease. Patients with de novo miN1M0 or miM1a disease may harbor more aggressive disease than those with miN1M0 or miM1a disease at recurrence.

P3 | "In pre-treatment biopsy samples from a randomized Phase 3 trial cohort, GC demonstrated its ability to further risk stratify clinically high-risk men demonstrating an independent association of GC score with DM and MFS. High-risk prostate cancer is a heterogeneous disease state and GC can improve risk stratification to help personalize shared decision-making. NRG-GU009/PREDICT-RT (NCT04513717) aims to determine the optimal therapy based on GC score for high-risk prostate cancer."

"There is minimal to moderate correlation between the 22-GC and GPS or CCP gene expression signatures tested. Therefore, these tests should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker."

P1; Not yet recruiting --> Recruiting

"Veracyte...announced that six abstracts highlighting new data from studies evaluating the company’s Decipher Prostate Genomic Classifier and related capabilities will be presented, three as oral presentations, at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2023 taking place October 1-4 in San Diego."

"Our data reveals that MRI-visible csPCas harbor more aggressive histomic and transcriptomic features than MRI-invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI."

"There is minimal to moderate correlation between the 22-GC and GPS or CCP gene expression signatures tested. Therefore, these tests should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker."

Higher Decipher scores were associated with distant metastasis on PSMA PET in both the de novo and recurrent setting. Transcriptomic differences in pathways related to proliferation, p53 status, and PAM50 classification were seen when comparing localized, node-positive, and distant metastatic disease. Patients with de novo miN1M0 or miM1a disease may harbor more aggressive disease than those with miN1M0 or miM1a disease at recurrence.