Lab 21 are currently working with MDxHealth to offer their SelectMDx assay, which helps to identify patients at increased risk for aggressive disease, thereby aiding in the selection of men for prostate biopsy.
SelectMDx provides the likelihood of detecting prostate cancer upon biopsy, and the probability for high-grade versus low-grade disease, with an area under the curve (AUC) of 0.89 (95% CI: 0.86-0.92).
High Risk men may benefit from prostate biopsy and early detection:
Low Risk men may avoid unnecessary invasive procedures with routine follow up and screening:
SelectMDx for Prostate Cancer is a reverse transcription PCR (RT-PCR) assay performed on post-DRE (digital rectal examination), first-void urine specimens from patients with clinical risk factors for prostate cancer, who are being considered for biopsy. The test measures the mRNA levels of the DLX1 and HOXC6 biomarkers, using KLK3 expression as internal reference, to aid in patient selection for prostate biopsy. Higher expression levels of DLX1 and HOXC6 mRNA are associated with an increased probability for high-grade (Gleason score (GS) ≥ 7) prostate cancer.
PSA screening has become a controversial subject within the medical community, with concerns about the identification of patients with indolent prostate cancer and overtreatment, leading to recommendations for elimination of its use in routine screening for prostate cancer. However PSA screening has improved early detection of prostate cancer, resulting in an increased likelihood for curative treatment. Many urologists are concerned about a return to the pre-PSA era, when the detection of advanced prostate cancer was far more common. Delayed diagnosis of prostate cancer will, in some instances, lead to poorer outcomes, and will inevitably result in greater healthcare costs to effectively treat these patients and lower quality of life.
Despite the negative perception of the PSA test, most urologists support its use as an early warning mechanism for the detection of prostate cancer, although it is clear the test has limitations. When PSA is utilized, men with a high or rising PSA may be subjected to a prostate biopsy. Urologists typically perform a transrectal ultrasound guided (TRUS) prostate biopsy for high-risk patients with an elevated or rising PSA level, obtaining approximately 10 to 12 needle-core tissue samples according to the current standard of care.
Of note, an abnormal PSA result can often be caused by factors other than cancer, including infection, inflammation, or other benign conditions, such as benign prostatic hyperplasia (BPH). This leads to the inclusion of many men without cancer among those who are being subjected to prostate biopsies, i.e. false-positive PSA screening. However, because of the semi-random and limited nature of sampling of the prostate during biopsy, many cancers are undetected by histopathologic review. Studies by urology and pathology opinion leaders report that initial prostate biopsy histopathology has a 20% to 30% chance of missing a tumor, i.e. the biopsy false-negative rate.
Of the nearly 2 million prostate biopsies performed each year, less than a third find cancer, due to false-positive PSA results. Most of these men could have avoided a painful and invasive prostate biopsy procedure, with its associated side effects and costs.
SelectMDx for Prostate Cancer is a proprietary urine-based, molecular test that offers a non-invasive, ‘liquid biopsy’ method to identify a patient’s risk for prostate cancer, helping to both reduce unnecessary prostate biopsy procedures with their concomitant complications and expenses, and to identify those men at increased risk of harboring high-grade disease who may benefit most from earlier detection.
The SelectMDx assay has been analytically validated and results have been compiled for publication. The analytical validation consisted of summaries of the Analytical Specificity, Analytical Sensitivity, Cross-Reactivities, Interference, Limits of Quantification and Detection, Linearity, Measurable analyte range, Reproducibility and Repeatability and test Robustness. All measurements met the internal criteria to satisfy the successful analytical validation of the assay.
For optimal clinical performance of SelectMDx a molecular biomarker algorithm was developed and validated in two prospective independent cohorts using post-DRE, first-void urine specimens collected from multiple clinics. This algorithm is based on a combination of the mRNA biomarkers and traditional clinical parameters like PSA, PSA density, DRE, age and family history of prostate cancer, and is designed to help identify patients likely to have high-grade prostate cancer detected upon biopsy (GS ≥ 7). The samples were collected after DRE from men with elevated serum PSA levels (in conjunction with potentially an abnormal DRE or family history) who were scheduled for a prostate biopsy because of suspicion of prostate cancer. The first cohort of 519 samples was used as training set for the development of the prostate cancer risk score, which was subsequently validated in a second cohort of urine samples of 386 men. The risk score based on the 2-gene mRNA urine assay combined with the available traditional clinical risk factors resulted in a significantly better patient risk stratification compared to current methods in clinical practice and segregates patients into their chances of harboring no, low-grade or high-grade prostate cancer.
- Van Neste et al, Detection of High-Grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. European Urology 2016.
- Leyten et al, 2015, Clinical Cancer Research, 21-13, pg. 3061-3070. Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer.
- Pfafll, 2001, Nucleic Acid research, 29-9, pg. 2002-2007. A new mathematical model for relative quantification in real-time RT-PCR.
- Lucia et al, 2008, Cancer Prev Res, 167-173. Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention.
- Dijkstra et al, Validation of a New Urine Test for the Early Diagnosis of Clinically Significant Prostate Cancer. Proceedings from SIU 2015, MP0302, p10.
- Guidelines EAU (European Association of Urology: www.uroweb.org)
- Richtlijnen NVU (Nederlandse vereniging voor Urologen: www.nvu.nl)
- Guidelines NVU (Dutch Society of Urologists)