Clinical Diagnostics - Prostate

Prostate cancer is the most frequent cancer in men, with an estimated 217,730 new cases diagnosed for 2010 in the United States.

Cancer Facts and Figures 2010.

Although prostate cancer is one of the deadliest cancers in men, its accurate diagnosis and follow-up remain a challenge and come at a considerable cost to the healthcare system.

Prostate cancer is most commonly screened by performing a Prostate-Specific Antigen (PSA) blood test together with a Digital Rectal Exam (DRE). A biopsy is subsequently performed to determine if either of these initial tests is abnormal. Unfortunately, this standard of care has resulted in over-diagnosing and over-treatment of prostate cancer. An abnormal PSA result is often caused by other factors including age, infection, inflammation, or other benign conditions such as benign prostatic hypertrophy (BPH). Approximately 75% of men who undergo an initial prostate biopsy due to elevated PSA are found to have a negative biopsy. On the other hand, prostate biopsies still miss many cancers and thus cannot conclusively rule-out healthy men from further testing. As doctors are unable to say with confidence that these patients are cancer free, active follow-up including re-biopsy is usually recommended resulting in unnecessary testing on more than 1 million cancer-free men annually.

In addition, not all cancer cells detected after biopsy are clinically significant. Pathology staging by histopathology is often inaccurate whereby the majority of cancer is classified as low to intermediate risk for progression. As a result patients are confronted with the difficult decision about whether to undergo cancer treatment with life-long side effects, while in many cases the disease will not have a significant impact.

MDxHealth is developing two products for prostate cancer to augment the accuracy of current diagnostic methods and to help identify aggressive disease.

Globocan 2008

Products

ConfirmMDx for Prostate Cancer is a molecular diagnostic test that provides physicians with a tool to assist with the identification of cancer in men who have undergone a biopsy procedure and are shown to have an elevated PSA level, abnormal DRE or BPH. The test provides physicians with an important tool for assessing the presence or absence of cancer cells in biopsy tissue, ruling out healthy men from undergoing unnecessary repeat biopsies or excessive screening procedures.

The false negative rate of histopathology missing cancer due to sampling errors is reported to be 25 -30%. MDxHealth has previously reported on positive results concluding that “due to the high Negative Predictive Value (96%) of methylation markers they could be used to avoid unnecessary repeat biopsy in ~30% of men with negative initial biopsy and high risk features.”(see Troyer, etc. al. and Trock et. al. below). The test could be used on approximately 750,000 men in the US who have a negative biopsy on the same sample material as the initial biopsy, therefore avoiding an additional doctor visit for the patient.

InformMDx for Prostate Cancer is a molecular prognostic test that will provides physicians with a tool to aid in the assessment of the patient’s prognosis by determining the aggressiveness of the tumor. This information, in conjunction with Gleason scores of the biopsy, will help to distinguish patients who require more aggressive treatment from those who are at lower risk of disease progression and may be candidates for active surveillance under the care of an urologist.

Decisions on patient management after a diagnosis of prostate cancer are generally based on the positive diagnosis of biopsy tissue. However, evidence of aggressive cancer cells is often lacking in the biopsy tissue extracted for analysis, and is only detected in surgical samples after prostatectomy. The failure to detect aggressive cancer cells in prostate biopsies frequently results in aggressive treatment in men. A molecular test that provides an accurate diagnosis of cancer involvement and tumor aggressiveness in prostate biopsies may dramatically reduce such overtreatment.

Literature

Trock, B.J., Brotsman, M., Mangold, L.A., Gurganus, R., McAskill, T., Epstein, J.I., McLeod, D., Klein, E.A., Jones, S.J., Wang, S., Bigley, J.W., Mehtrota, J., Mazumber, A., Raghavan, B., Wang, H., Vener, T., Vargo, J.M., Partin, A.W. DNA methylation as a biomarker to evaluate histologically negative prostate biopsies in high-risk men. Submitted to Urology SEP 2010.

Troyer, D., Lucia, S., de Bruine, A., Mendez-Meza, R., Dunscomb, N., van England, M., McAskill, T., Bierau, K., Louwagie, J., Bigley, J. Prostate Cancer Detected by Methylated Gene Markers in Histopathologically Cancer-Negative Tissues from Men with Subsequent Positive Biopsies. Cancer Epidemiology, Biomarkers and Prevention, 2009 18(10): 68 - 74.

Gaston, S.M., Guerra, A., Meadows, J., Bigley, J., Renard, I., Louwagie, J., Bierau, K.Molecular Biomarker Analysis of Clinical Prostate Biopsy Specimens: Tissue Print Techniques Simplify Development of DNA Methylation Marker Tests while Preserving the FFPE Specimen for Histology. Abstract 129. EORTC-NCI-ASCO Conference on Molecular Cancer Markers, October 15-17, 2009, Brussels, Belgium.

Vener, T., Derecho, C., Varde, S., Mazumder, A., Grooteclaes, M., Bierau, K., Louwagie, J., Bigley J., de Leval, L., Gaspar, Y., Coppens, L., de Leval, J., and Waltregny, D. A non-invasive urine-based research test for the detection of prostate cancer using DNA methylation. 2007 Annual AACR meeting, April 2007, Los Angeles, CA.

Woodson K, O'Reilly KJ, Hanson JC, Nelson D, Walk EL, Tangrea JA. The usefulness of the detection of GSTP1 methylation in urine as a biomarker in the diagnosis of prostate cancer. J Urol. 2008;179(2):508-11;

Henrique R, Ribeiro FR, Fonseca D, Hoque MO, Carvalho AL, Costa VL, Pinto M, Oliveira J, Teixeira MR, Sidransky D, Jerónimo C. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin Cancer Res. 2007;13(20):6122-9.

Rogers CG, Gonzalgo ML, Yan G, Bastian PJ, Chan DY, Nelson WG, Pavlovich CP. High concordance of gene methylation in post-digital rectal examination and post-biopsy urine samples for prostate cancer detection. J Urol. 2006;176(5):2280-4.

Henrique R, Jeronimo C, Teixeira MR, Hoque MO, Carvalho AL, Pais I, Ribeiro FR, Oliveira J, Lopes C, Sidransky D. Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues for clonal progression in prostate carcinogenesis. Mol Cancer Res. 2006;4(1):1-8.

MDxHealth’s products are not currently cleared or approved by the FDA.