TEST:

Decipher Prostate Cancer Test

P2, N=324, Active, not recruiting, NRG Oncology | Trial completion date: Oct 2028 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice.

TBx samples yield higher genomic scores than SBx samples, with grade influencing the association between PI-RADS score and genomic risk. For the GG 1 subgroup, there was no correlation between PI-RADS and genomic scores. These findings need further validation to assess the impact of TBx on genomic risk assessment in active surveillance.

"Veracyte, Inc...today announced that its market-leading Decipher Prostate Genomic Classifier is the only gene expression test to be included in version 1 of the 2025 NCCN* Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as part of the updated “Advanced Tools” table located in the Principles of Risk Stratification and Biomarkers section (PROS-H) ."

In a prospective AS trial, the genomic classifiers – Decipher GC and the derived CCP and GPS signatures – showed no clinically relevant differences between GG1 biopsy cores with and without coexisting higher-grade cancer elsewhere in the prostate. The slightly higher values observed in the GPS signature are insufficient to support any clinical application but merit further investigation. Findings suggest that prostate cancer foci are heterogeneous and genomically independent, and results from any particular core are more reflective of the region sampled, rather than informing on the risk of missed higher-grade cancer elsewhere in the gland

Based on our analysis, elevated risk evaluations during AS inititiation by Decipher GC (≥0.45) and mpMRI (PI-RADS 4-5) were weakly correlated (τb = 0.13), which suggests that imaging and genomic features capture distinct, complementary prognostic information and should ideally be combined given that both initial Decipher GC ≥0.45 and PI-RADS 4-5 were associated with progression to treatment. Our results validate a Decipher GC ≥0.45 as an independent predictor for AS progression in patients across PI-RADS classification, while mpMRI PI-RADS 4-5 was not when Decipher GC ≥0.45. As such, an individualized approach to surveillance is augmented by Decipher GC testing, even for men with concerning mpMRI (e.g., PI-RADS 4-5).

Available models predicting LNI are historically based on clinical parameters and not on GC. Our novel nomogram including data from recently adopted GC can be used to quantify the risk of LNI and guide intraoperative decisions on lymph node dissection optimizing for postoperative complications and oncological control.

Similarly, PSC basal-luminal shows the basal neuroendocrine-like is much higher in Israeli cohort 27% vs 7.5% (p=0.004). Conclusions These preliminary results suggest that geographic variation of decipher genomic classifier risk score in patients with early prostate cancer may exist, and correlate with differences in transcriptomic profile, including androgen receptor activity, p53 mutation, pTEN tumor suppressor gene deletion, and basal-luminal biologic phenotype.

GC testing impacts adjuvant therapy administration when viewed through the risk categories presented in the patient report; however, these data do not provide specific support for GC testing in the adjuvant treatment setting.

P=Obs | N=240 | VANDAAM (NCT02723734) | "Veracyte, Inc...announced that new data from the multicenter, prospective VANDAAM trial show that the Decipher Prostate Genomic Classifier accurately predicts aggressive prostate cancer among African American men with early-stage disease....Following standard treatment, patients with high Decipher test scores were eight times more likely to have biochemical recurrence within 2 years (BCR; i.e., a rise of prostate-specific antigen levels in the blood, which was used as a surrogate for aggressive disease), compared to those with lower genomic test scores (HR = 7.93, 95% CI, 1.65 – 33.04, p = 0.008). When adjusted for other variables, such as age, race, pre-treatment prostate specific antigen (PSA), and Gleason score, those patients with high Decipher test scores remained at significantly high risk of rapid-onset BCR (HR = 10.37, 95% CI, 1.94-55.35, p = .006)."

P=N/A; Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Apr 2024

Conclusions Herein, we showed that the higher GC score was associated with risk of csPCa recurrence post-FT. Patients with low-risk GC and luminal differentiated csPCa may be ideal candidates for FT.

P2/3 | N=11,922 | STAMPEDE (NCT00268476) | "In the new study, researchers analyzed data for 1,523 patients with advanced or metastatic prostate cancer who were followed in the STAMPEDE trial for a median of 14 years. They found that higher Decipher Prostate test scores were associated with an increased risk of death in both groups. Additionally, among the 832 patients with metastatic disease, only those with higher Decipher Prostate scores received a significant survival benefit from the addition of docetaxel to ADT. These patients had a 36% reduction in risk of death (HR 0.64, 95% CI, 0.48-0.86) with the addition of docetaxel as compared to those with lower Decipher scores who did not significantly benefit (HR 0.96, 0.71-1.30; interaction p=0.039)."

PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI's SEER Program enables scientists to investigate numerous research inquiries.

This real-world study of a novel transcriptomic linkage conducted at a national scale supports the external prognostic validity of the Decipher GC among patients managed in contemporary practice.

Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.

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Men who underwent GC testing were more likely to undergo conservative management. GC testing at biopsy is prognostic of adverse pathologic outcomes in a large population-based registry.

"Active surveillance has emerged as a preferred strategy for managing low-risk prostate cancer, and tissue-based biomarkers play a crucial role in refining patient selection and risk stratification. Standardization and validation of these biomarkers are essential to ensure their widespread clinical use and optimize patient outcomes."

In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.

P2; Not yet recruiting --> Recruiting | Initiation date: Dec 2024 --> Mar 2024

"Veracyte...announced that data from 14 presentations at AUA 2024, the annual meeting of the American Urological Association, show that the Decipher Prostate and Decipher Bladder Genomic Classifiers provide better prognostic information for patients with prostate and bladder cancer, compared to standard approaches. They also show that the research-use-only Decipher GRID (Genomic Resource for Intelligent Discovery) tool is helping to advance scientific understanding of these diseases. The findings were presented during the conference taking place May 3-6 in San Antonio."

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)."

P=N/A | N=900 | Recruiting | Sponsor: University of Michigan Rogel Cancer Center | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

"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; 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.

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.

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.

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.

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.

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.