IRVINE, Calif.—MDxHealth SA recently announced the presentation of data at the ASCO Genitourinary Cancers Symposium 2015 in Florida demonstrating the prognostic value of its ConfirmMDx for Prostate Cancer test, noting that the data support the ability to predict the presence of clinically significant cancer in biopsy-negative patients based on the DNA hypermethylation of the biomarkers in the ConfirmMDx test.
“Methylation is a DNA-based control mechanism that regulates gene expression,” explains Dr. Jan Groen, CEO of MDxHealth. “Hypermethylation of key genes, such as tumor suppressor genes, is associated with the presence and development of cancer. The pattern of gene hypermethylation in tumor cells is often specific to [a cancer of] the tissue of origin and can be used to improve cancer detection, assess prognosis—for example, risk of recurrence—and predict a tumor’s response to therapy.”
ConfirmMDx for Prostate Cancer is an epigenetic test that was developed and validated to rule out the presence of undetected cancer in men with benign prostate biopsy results. The study reported on in Florida was designed to evaluate if those patients testing positive for ConfirmMDx could be further stratified for the risk for clinically significant cancer. A total of 102 patients with either no cancer or prostate cancer with a Gleason score (GS) of 6 or 7 were tested with the ConfirmMDx test. The results showed that the intensity of the DNA hypermethylation in benign needle biopsy cores is higher in patients with GS7 cancer compared to those with GS6 cancer alone. These findings support the feasibility of an algorithm that is sensitive to the GS of undetected foci of aggressive prostate cancer and could translate into a prognostic score to help stratify patients eligible for active surveillance from those who may benefit from earlier intervention.
The three biomarkers in the test and study are GSTP1, APC and RASSF1. All three genes have been identified as important prostate cancer markers. GSTP1, Groen notes, likely the most prostate cancer-specific, is involved in DNA detoxification, with APC involved in apoptosis and RASSF1 in cell cycle regulation.
“For all three ConfirmMDx biomarkers, we observed a positive correlation between the highest level of DNA hypermethylation in the adjacent benign cores with the cancer cores from the same patient,” reported Dr. Sandra M. Gaston, director of urological research at New England Baptist Hospital and director of the Molecular Biomarkers Research Laboratory in the department of pathology and laboratory medicine at Tufts Medical Center in Boston. “These results suggest that risk stratification predicting the presence of clinically significant cancer in biopsy-negative patients based on the DNA hypermethylation of the ConfirmMDx genes is feasible.”
“These data clearly support the prognostic power of the ConfirmMDx genes. The addition of a risk score for ConfirmMDx methylated patients, which enhances the test’s positive predictive value, will provide deeper insights into a patient’s risk for undetected clinically significant cancer,” according to Groen. “The urology community has widely adopted ConfirmMDx for its ability to reduce unnecessary repeat biopsies, and these data will further augment the assay’s clinical utility by aiding in the identification of patients who may benefit from early detection and treatment.”
More than 975,000 American men are diagnosed with a negative prostate biopsy each year; however, approximately 25 to 35 percent of those men receive false-negative results. Under the current standard of care, prostate biopsy procedures consisting of 10 to 12 needle biopsy cores only sample approximately 1 percent of a man’s prostate. This approach leaves men at risk of undetected cancer, leading to a high rate of repeat biopsies, even for cancer-free men. There is an unmet medical need for a clinically effective diagnostic test to address this dilemma. ConfirmMDx for Prostate Cancer is able to detect an epigenetic field effect or “halo” associated with the cancerization process at the DNA level. This halo around a cancer lesion can be present despite cells having a normal appearance under the microscope. Thus, ConfirmMDx for Prostate Cancer can potentially aid urologists in identifying truly negative men who may forego an unnecessary repeat biopsy procedure.
In terms of what’s next, Groen notes that “MDxHealth has developed a liquid biopsy epigenetic test called ConfirmMDx for Bladder Cancer. Data from a clinical utility study using the test is scheduled for read-out in 2015. ConfirmMDx for Bladder Cancer is performed on urine samples to rule out bladder cancer in patients diagnosed with hematuria, who are traditionally followed with cytology and cystoscopy.”
