TEST:

SelectMDx

Methodology: A descriptive research centered on genetic biomarkers associated with the diagnosis of prostate cancer was conducted.The selection of articles comprised the period from 2019 to 2024, using as an inclusion criterion those available in the PubMed database, from the descriptor: Prostate cancer biomarkers being 519 articles, being selected only 15 Results Over the years, several studies have identified genetic tests such as BRCA1 and BRCA2, capable of identifying patients at high risk of developing prostate cancer.These findings culminated in the identification of new genetic biomarkers, categorized as blood and urinary.Urinary markers, such as Select MDX, MIPS, Exodx Prostate and PCA3-PCGm1, improve early diagnosis, reducing the need for invasive prostate biopsies, dispensing rectal touch.Already the blood markers, exemplified by the 4kscore test, associate themselves with algorithms, expanding their potential when employed in conjunction with magnetic resonance imaging and the prostate health index. Conclusion The introduction of genetic biomarkers in the context of prostate cancer represents a significant advance, providing subsidies to improve the detection, diagnosis and risk assessment associated with this neoplasia.Its application in clinical practice emerges as a facilitating tool in decision making regarding the indication of biopsies and rebiopsies, contributing to the reduction of invasive procedures and giving greater accuracy to the diagnostic process.

SelectMDx appears to have moderate to good diagnostic accuracy in differentiating patients with clinically significant prostate cancer from people at high risk of developing prostate cancer. Higher-quality clinical studies assessing the diagnostic accuracy of SelectMDx for clinically significant cancer are still needed.

We also briefly discuss a few promising biofluid marker candidates (DNA methylation, micro-RNAs) which are not in clinical application. As no single assay is perfect, we envision that a combination of biomarkers, together with imaging, will become the preferred practice.

Long-term clinical PrCa outcomes will be collected annually until the study closes. Clinical trial information: NCT04472338.

Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers.

SelectMDX® score includes genomic markers, age, PSA, prostate volume, and digital rectal examination. Several studies showed consistence in the ability to improve detection of csPCa, avoidance of unnecessary prostate biopsies, helpful in decision making for clinical benefit of PCa patients with future well designed, and impactful studies.

"MDxHealth...announced that Cigna has expanded commercial and Medicare Advantage coverage to include the Company’s Select mdx for Prostate Cancer test. With the addition of Select mdx, Cigna will now provide insurance coverage across mdxhealth’s full menu of precision diagnostic cancer tests, including its Confirm mdx and Genomic Prostate Score (GPS) tests."

Studies on prostate cancer reported in the meetings mainly focus on the advances of diagnostic biomarkers (such as α-2, 3-1inked sialylation of terminal N-glycan on free PSA density, SelectMDx) and imaging techniques [such as multiparametric magnetic resonance imaging, prostate specific membrane antigen(PSMA)-PET/CT], the new method for prostate biopsy, the new treatments of prostate cancer including [Lu] Ludotadipep and DROP-IN PSMA probe, and the prognosis assessment of prostate cancer (such as AR-V7). This article provides an overview on the research hotspots of three international academic meetings.

Coverage of novel CaP biomarkers are relatively robust for Medicare plans but sparse for non-Medicare plans, with the majority of non-Medicare plans requiring prior authorization. Non-Medicare eligible men may face significant barriers to obtaining these tests.

Application of SelectMDx results in better health outcomes and cost savings. The value of SelectMDx was highest when used before MRI to select patients for MRI and subsequent biopsy.

"MDxHealth...received notice that its Select mdx for Prostate Cancer test has successfully completed a rigorous technical assessment process with the Molecular Diagnostics Services (MolDX) Program developed by Palmetto GBA. Select mdx will be reimbursed throughout the U.S. for Medicare patients who meet coverage conditions under the foundational Local Coverage Determination (LCD) for Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer."

PSA is currently the most widely used biomarker as a screening method for prostate cancer. Additional studies of new biomarkers in patients need to be evaluated for better screening and thus clinical management.

Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.

We found that screening men at high genetic risk for PCa must be based on mpMRI without pre-screening based on PSA>3ng/mL, to avoid missing too much ISUP>1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or PSAD≥0.1ng/mL/cc when mpMRI was negative increased the detection of ISUP>1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from 40 years-old.

To further explore the diagnostic value of different urinary markers in the screening of PCa patients. https://inplasy.com/, identifier INPLASY202290094.

It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95-100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14-33% of men without PCa or insignificant PCa.

Combining SelectMDx and mpMRI PI-PADS scores of 4/5 may be useful for PCa biopsy decision-making.

The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.

The potential number of reduced biopsies in clinical use was 40,72% using the SelectMDx test, assuming a negative SelectMDx test resulted in the decision not to biopsy the patient. This is higher compared to the validation cohort, which is explained by differences in patient population.

Serum, urine, and tissue-based biomarkers are increasingly being incorporated into the clinical care paradigm, but there is still a limited understanding of how to use them most effectively. In the current article, we review test characteristics and clinical performance data for both serum [4 K score, prostate health index (phi)] and urine [SelectMDx, ExoDx Prostate Intelliscore, MyProstateScore (MPS), and PCa antigen 3 (PCA3)] biomarkers to aid decisions regarding initial or repeat biopsies as well as tissue-based biomarkers (Confirm MDx, Decipher, Oncotype Dx, and Polaris) aimed at risk stratifying patients and identifying those patients most likely to benefit from treatment versus surveillance or monotherapy versus multi-modal therapy.

In 59.5% of the patients a prostate carcinoma was detected in the biopsy, in 40.6% of the cases a clinically significant prostate carcinoma (Gleason ≥7). The SelectMDx® score was significantly higher in patients with a positive biopsy result (49.07 ± 25.99% vs. 22.00 ± 26.43%; p < 0.001).

No abstracts available

"MDxHealth SA...announces that Palmetto GBA, a Medicare Administrative Contractor (MAC) that assesses molecular diagnostic technologies under its MolDX program, has finalized a foundational Local Coverage Determination (LCD) for Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer that covers the indication for our SelectMDx® for Prostate Cancer test. The foundational LCD identifies evidence supporting the clinical utility of our SelectMDx test and, when the LCD becomes effective on July 3, 2022, is expected to support coverage of our test for qualified Medicare patients throughout the United States."

P2; Recruiting --> Completed | Trial completion date: Dec 2022 --> May 2022 | Trial primary completion date: Dec 2022 --> May 2022

The performance of SelectMDx is comparable to that of mpMRI with regards to PCa and HG-PCa detection. In addition, this biomarker could help refine the clinical decision-making regarding the necessity of a biopsy in patients suspected to has been PCa.

Conclusions : SelectMDx revealed to be a good predictor of PCa, while, with regards to csPCa detection, it demonstrated to be less effective, showing results similar to mpMRI. Biopsy could be proposed to all cases of mpMRI PI-RADS 4-5 score and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 score followed by a positive SelectMDx.

These results support the use of SelectMDx to help identify men for WW or AS following TRUS biopsy. Study results also support the use of non-invasive tests to help identify men with HGPCa who may benefit from prostate biopsy, thereby reducing over-detection of indolent disease.

The use of urinary biomarkers hasimproved of clinically significant prostate cancerdiagnosis. Their use reduces the number of unnecessarybiopsies and avoids overtreatment of indolentprostate cancer.

"Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry."

"This is only the 2 nd study and the largest study to date to evaluate SelectMDx in an AS cohort. SelectMDx score was associated with a more than 4-fold increase in risk of rapid upgrading, even after adjusting for known prognostic factors, and the effect was particularly strong in men meeting the criteria for very low risk (GG=1, no more than 2 positive cores, <50% of any core involved with cancer, and PSA density<0.15). Evaluation of this non-invasive test is warranted as a potential means of monitoring AS patients during follow-up, to reduce biopsy frequency and the need for expensive MRIs."

"Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors, patient's ethnicity, cost of the test, patient life-expectancy, and patient goals. There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging, polygenic single-nucleotide panels, IsoPSA, and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening."

Despite major improvements and innovations in prostate cancer biomarkers, application in current clinical practice is limited. However, these biomarkers have an important role in determining risk, preventing unnecessary prostate biopsies, and predicting prognoses. Additional confirmatory studies will be needed to fully understand the impact of prostate cancer-specific biomarkers.

"In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index, SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches - circulating tumour cells and cell-free DNA - with a potential role in metastatic castration-resistant prostate cancer and will briefly give some future perspectives, mostly outlooking epigenetic markers."

"Published data were used to compute the number of unnecessary biopsies avoided and number of GG ≥2 cancers missed if the biomarker had been used clinically to select for prostate biopsy. The evidence review is preceded by a primer on these and other clinically-relevant summary statistics."

Financial issues and the absence of SelectMDx in professional guidelines and hospital care pathways also hampered its use. Eliciting users' and nonusers' views is important to better understand how biomarker tests can be embedded in clinical practice.

In combination with traditional factors like age and baseline PSA, the stepwise addition of OPKO4K combined with ExoDx test significantly improves decision for the need of prostate biopsy. Incorporation of both tests prior to MRI provides outstanding discrimination between men with a low versus high probability of positive prostate biopsy. Utilizing MRI with combination of biomarkers has high predictive capability in men with elevated PSA.

"Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice."

These early data support the feasibility of opening a dedicated clinic for men at high genetic risk of prostate cancer. This early report on the initial enrollment of our long-term study will help optimize early detection protocols and provide evidence for personalized prostate cancer screening in men with key pathogenic germline variants.

Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3-10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.

In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.

SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

In this real-life selected group of consecutive patients with a confirmed positive PCa biopsy and available mpMRI, the liquid biopsy test with SelectMDx, did not provide an additional information about the PCa clinical significance. The addition of SelectMDx was only found valuable in those patients who had a very high-risk PCa (ie, GS ≥8) who had a positive SelectMDx test outcome despite of a negative mpMRI outcome.