TEST:

Prolaris®

There is no consistent association between MRI-visible cancer and Prolaris risk profile. When utilizing multigene molecular testing in prostate cancer, each individual patient must be evaluated to decide the appropriate level of care.

Correlation between 22-gene GC and either GPS-derived or CCP-derived signatures is minimal to moderate. These tests are not interchangeable, and their use should be guided by the specific evidence supporting each signature.

CCP test may be a useful tool to estimate the risk of progression in PCa patients and guide the decision between AS and active treatment. Triple hit phenotype or TMPRSS:ERG fusion status was not associated with progression.

Tissue-based genomic tests, such as Decipher, Oncotype DX (GPS), and Prolaris, have emerged as prognostic tools for assessing tumor aggressiveness and metastatic potential. Current evidence supports Decipher's prognostic capabilities with studies demonstrating risk stratification while further research is needed for Prolaris and GPS to solidify their role in PCa risk stratification. These assays are intended to guide therapeutic choices, reducing overtreatment in low-risk cases while identifying high-risk patients who may benefit from more aggressive or definitive intervention. Despite growing clinical adoption, challenges such as cost, disparities in access, and variability in physician utilization still remain. Further prospective studies and randomized trials are required to optimize clinical implementation and validate the long-term impact of genomic testing on PCa outcomes.

Genomic classifiers and AI-based digital histopathology models might have superior prognostic and predictive value compared to established clinical and pathological parameters in localized, recurrent, and metastatic PCa. Despite promising results, prospective validation of these biomarkers in randomized trials remains limited. This review underscores the need for further prospective trials to confirm the usefulness of these biomarkers in PCa.

By assessing genetic mutations (e.g. BRCA1, BRCA2 genes, single nucleotide polymorphism) or the presence of splice variants of the androgen receptor (ARV7), we are able to identify patients in whom the planned treatment may be expected to be ineffective and thus choose other treatment modalities. In the present review article, we offer a comprehensive overview of current diagnostic tests that find application in the diagnosis of early and advanced prostate cancer.

P=N/A, N=140, Active, not recruiting, British Columbia Cancer Agency | Recruiting --> Active, not recruiting

"Myriad Genetics...and PATHOMIQ, Inc...announced that they have entered into a strategic collaboration for Myriad to exclusively license PATHOMIQ_PRAD, PATHOMIQ’s AI technology platform for prostate cancer, in the United States."

Department of Veterans Affairs. (PROSPERO: CRD42022347950).

P=N/A, N=500, Active, not recruiting, Myriad Genetic Laboratories, Inc. | Recruiting --> Active, not recruiting

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.

"Myriad Genetics, Inc...announced that its Prolaris prostate cancer prognostic test continues to be classified by the National Comprehensive Cancer Network (NCCN) as an ‘Advanced Tool’ in the fight against prostate cancer. Like other gene expression-based tests, Prolaris for many years has been included in NCCN guidelines with category 2A level of evidence, meaning its inclusion has support from at least 85% of members on the NCCN prostate panel."

In-field and overall recurrence rate on biopsy one year after HIFU was found to be 42% and 56%, respectively. GG3 or greater disease trended towards in-field disease recurrence and increased pre-HIFU PSA was associated with overall disease recurrence. No significant changes in sexual or urinary symptoms were observed.

Prolaris added significant information to clinical risk stratification to aid in treatment decision making. Intermediate-risk prostate cancer patients who were recommended to AS by Prolaris were more likely to initially pursue AS and were more likely to remain on AS at 3 years post-diagnosis than patients recommended to DT.

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.

"Eurobio Scientific...announces the finalisation of its agreement with Myriad Genetics to acquire the EndoPredict genomic test. As part of the agreement announced on 7 May 2024...on 1 August 2024 the Group has completed the acquisition of the second-generation genomic test EndoPredict for breast cancer and the license agreement to distribute the second-generation genomic test Prolaris for prostate cancer from Myriad Genetics. Revenues from these two activities are around €8m on an annual basis, with EBITDA levels in the short and medium term diluting the Group's performance."

"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."

"Myriad Genetics...announced that JCO Precision Oncology has published a study showing a clinical cell-cycle risk (CCR) score can accurately predict the benefit of adding androgen deprivation therapy (ADT) to radiation therapy (RT) in men with localized prostate cancer."

The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.

"Myriad Genetics, Inc...announced the reorganization of its European operations to better align company resources to its domestic opportunities while continuing to serve key biopharma partners and patients outside the United States."

AS is an option for favorable prostate cancer. We show that there was no difference in Biomarkers, PIRADS, and PSAD between the treated and the AS group. Escalation to treatment from AS should be a shared decision making between provider and patient.

Unfortunately, methods within clinical routine today do not allow molecular subclassification of prostate cancer. To enable comparison of the most promising treatment-predictive biomarkers and to evaluate the health economic value of implementing such precision medicine for prostate cancer, a prospective study is being planned as a joint initiative in Sweden that aims to evaluate and validate biomarkers and to establish a study platform for adaptive biomarker-driven clinical trials (sprintr.se).

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

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.

45th Annual Raymond James Institutional Investors Conference

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.

GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes.

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."

P=N/A; Phase classification: P3 --> P=N/A

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.

For patients with NCCN intermediate-risk PCa who were identified by genomic testing as candidates for AS, AS is safe based on the very low observed metastasis risk. The CCR score is a strong predictor of metastasis beyond clinicopathologic factors.

"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."

Our findings are congruent with other studies in highlighting the high degree of multifocality and bilateral disease in men with prostate cancer. GRS did not improve our ability to select for focal disease. This emphasizes the importance of continuing to work to improve patient selection parameters for focal therapy.

"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."

"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."

"Myriad Genetics, Inc...announced the integration of Absolute Risk Reduction (ARR) into the Prolaris^® Prostate Cancer Prognostic Test to help patients and providers make personalized treatment decisions regarding hormone therapy. Prolaris is the only biomarker test to quantify the benefits of adding androgen deprivation therapy (ADT) to radiation therapy (RT)."

"Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited."

Mycophenolate mofetil was switched to everolimus, and he was referred to dermatology...Before he could pursue recommended treatments, he was admitted in November 2021 for fever, worsening back pain, leukocytosis (WBC 131.6 thousand/µL; increased from 7.3 thousand/µL in October 2021), anemia (6 gm/dL), and thrombocytopenia (17 thousand/µL)... Chronic immunosuppression impairs anti-tumor immune surveillance and has a central role in oncogenesis after solid organ transplant. LT recipients receive even more immunosuppression. Immunosuppression modification with mammalian target of rapamycin inhibitors (everolimus) may interfere with cancer cell proliferation and angiogenesis.

The Prolaris test can accurately predict an individual's benefit of adding ADT to RT, and the risk threshold is consistent with patient attitudes about when to use or omit ADT. 1. Spratt DE, Tward JD: IJROBP 108:899-902, 2020.