MDxHealth's ConfirmMDx Genes Identify Prostate Cancer Aggressiveness in Diagnostic Biopsies

The gist: Earlier this year, we posted about a new test that could reduce the need for multiple biopsies to accurately diagnose men with prostate cancer. Now, the company that makes the test, called ConfirmMDx, reports that the results of the test for a given patient strongly correlate with already-established measurements, such as Gleason Score (GS). This supports the use of the test to help diagnose and determine the severity of prostate cancer.

MDxHealth SA (NYSE Euronext: MDXH), a leading molecular diagnostic company that develops and commercializes epigenetic tests to improve the diagnosis and treatment of cancer patients, today announced positive data from an important study confirming the ability of the ConfirmMDx® genes to identify prostate cancer (PCa) aggressiveness in diagnostic biopsies. The data, presented at the European Association of Urology, Section Urological Research (ESUR) meeting in Glasgow, UK (October 9-11, 2014), confirmed that the epigenetic profile of ConfirmMDx genes generated by the test is strongly correlated with established risk stratification metrics, such as Gleason Score (GS) and the NCCN (National Comprehensive Cancer Network) risk categories.

” ‘These data demonstrate that ConfirmMDx for Prostate Cancer not only provides important diagnostic information to help guide the decision on repeat biopsy, but that the genes may also deliver significant prognostic value, potentially determining whether a man has an aggressive or non-aggressive form of prostate cancer,’ noted Sandra M. Gaston PhD, 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 Massachusetts. ‘This study suggests that the epigenetic markers used in the ConfirmMDx test could have an expanded role in stratifying prostate biopsy patients by providing information that cannot be obtained from the histological examination of the tissue. The current ConfirmMDx test is highly sensitive for DNA hypermethylation of GSTP1, APC and RASSF1 in the tissue surrounding a prostate cancer. For men who have a histological diagnosis of “no cancer,” a negative result with the current ConfirmMDx test predicts that a subsequent biopsy will also be negative, identifying the majority of men who may avoid repeat biopsy. In this study, we found that hypermethylation of these markers is more intense in the tissue surrounding high grade prostate cancer potentially providing additional insights into the clinical significance of a potential undetected prostate cancer on methylation-positive patients.’ “

Circulating Tumor Cells Provide Genomic Snapshot of Breast Cancer

“The genetic fingerprint of a metastatic cancer is constantly changing, which means that the therapy that may have stopped a patient’s cancer growth today, won’t necessarily work tomorrow. Although doctors can continue to biopsy the cancer during the course of the treatment and send samples for genomic analysis, not all patients can receive repeat biopsies. Taking biopsies from metastatic cancer patients is an invasive procedure that it is frequently impossible due to the lack of accessible lesions. Research published October 10th in the journal Breast Cancer Research suggest that tumor cells circulating in the blood of metastatic patients could give as accurate a genomic read-out as tumor biopsies.

“Counting the number of circulating (CTCs) can tell us whether a patient’s cancer is aggressive, or whether it is stable and responding to therapy,” says the article’s first author Sandra V. Fernandez, Ph.D., assistant professor of Medical Oncology at Thomas Jefferson University. “Our work suggests that these in the blood also accurately reflect the genetic status of the parent tumor or its metastases, potentially giving us a new and easy to source of genomic information to guide treatment.”

Recommendations for Prostate Cancer Active Surveillance

“Prostate cancer is the second leading cause of cancer death in men in the United States. Active surveillance offers low-risk prostate cancer patients a means to avoid the potentially harmful side effects from treatment. Pathologists help determine patient eligibility for active surveillance and today a multi-specialty team published their recommendations for making such determinations in a special on-line posting from the Archives of Pathology & Laboratory Medicine.

“With active surveillance, patients undergo regular visits with prostate-specific antigen (PSA) tests and repeated prostate biopsies rather than aggressive treatment. It is distinguished from watchful waiting, in which treatment for localized disease is withheld and palliative treatment for systemic disease is initiated.

” ‘Active surveillance is an important management option for men with low-risk prostate cancer,’ says lead author Mahul Amin, MD, FCAP, Chair, Department of Pathology Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA. ‘Vital to this process is the critical role pathologic parameters play in identifying appropriate candidates for active surveillance.'”

Test Spares Men Unnecessary Biopsies for Prostate Cancer

Editor’s note: Some men must undergo more than one biopsy to accurately diagnose prostate cancer and assess its severity. Now, a test called ConfirmMDx can be used on tumor tissue from an initial biopsy to get a more detailed picture of a patient’s condition, reducing the likelihood that an extra biopsy will be needed. New studies show that the test could “lead to a 10-fold reduction in repeat biopsies.”

“In men with previous histopathologically negative findings, the epigenetic ConfirmMDx (MDxHealth) assay for prostate cancer can lead to a 10-fold reduction in repeat biopsies, 2 new studies show.

“Both confirm the utility of epigenetic profiling in helping to distinguish patients who have a true negative biopsy from those at risk for occult cancer, according to the researchers.

“The commercially available assay assesses methylation markers of prostate cancer (GSTP1APC, and RASSF1) to distinguish histologically benign biopsy cores from patients diagnosed with no cancer, low-volume cancer (a Gleason score of 6), or higher-volume cancer (a Gleason score of 7).

“One of the studies, a clinical utility field study in which the assay was tested by practicing urologists working in community settings, was published in the May issue of American Health & Drug Benefits.

New Accurate Epigenetic Test Could Eliminate Unnecessary Repeat Biopsies for Prostate Cancer

“More than one million prostate biopsies are performed each year in the U.S. alone, including many repeat biopsies for fear of cancer missed. Therefore there is a need to develop diagnostic tests that will help avoid unnecessary repeat biopsies. Two independent trials have now validated the performance of an epigenetic test that could provide physicians with a better tool to help eliminate unnecessary repeat prostate biopsies, report investigators in The Journal of Urology.

“In the previously reported independent MATLOC (Methylation Analysis To Locate Occult Cancer) trial, a multiplex epigenetic assay (ConfirmMDx for Prostate Cancer) profiling the APC, GSTP1 and RASSF1 genes demonstrated a negative predictive value of 90%. GSTP1 methylation is a specific biomarker for (prostate) cancer and this gene is methylated in up to 90% of prostate cancer cases. Additionally, APC and RASSF1 are important field effect markers and increase the diagnostic sensitivity of the assay.

“A second multicenter study, DOCUMENT (Detection Of Cancer Using Methylated Events in Negative Tissue), has validated the performance of the epigenetic assay used in the MATLOC trial as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. In the DOCUMENT study patients with a negative biopsy were evaluated to identify those at low risk for harboring cancer missed, through biopsy sampling error, who could forego an unnecessary repeat biopsy. The validation study resulted in a negative predictive value of 88%.”

Cancer Grading Gets an Upgrade

Cancer grading gets an upgrade

“Prostate cancer is the second most commonly diagnosed cancer among Canadian men but only about half of these cancers grow rapidly enough to require treatment.

“However, determining which prostate cancers need to be treated can be tricky because it’s hard to predict through biopsy which cancers will eventually become harmful. In fact, because biopsies often do not yield accurate information, between a third and half of patients initially diagnosed with harmless prostate cancers are likely to be “upgraded” to potentially harmful cancers within a year or two of diagnosis.

“A research team led by Dr. David Berman, a professor in the Department of Pathology and Molecular Medicine at Queen’s, and Dr. Tamara Lotan from Johns Hopkins University discovered that the decline of a specific protein within a tumour could help identify the tumours requiring treatment.

” ‘We have shown that a tumour-suppressing protein called phosphatase and tensin homolog, or PTEN, is lost most frequently in prostate tumours that will become harmful and require treatment,’ says Dr. Berman. ‘The team from Johns Hopkins has done a terrific job of making this test more reliable and valid and applicable to prostate cancer and to other forms of cancer.’ Currently, the Gleason Grading system is used to determine the harmful potential of prostate cancers. Scores usually range from 6 to 10, with lower numbers often indicating cancers that are unlikely to become harmful.”

Editor’s note: Read more about PTEN in our Top Biomarkers section.

Surgical Biopsy Proves Safe for Selected Late-Stage Lung Cancer Patients

“Researchers at UC Davis have determined that surgical biopsies can be safely performed on select patients with late-stage non-small cell lung cancer, which should enhance their access to drugs that target specific genetic mutations such as epidermal growth factor receptor (EGFR).

“The findings, published in the July issue of The Journal of Thoracic and Cardiovascular Surgery, address a common problem in treatment for advanced lung cancer: insufficient tumor tissue available for molecular analysis, which is required before prescribing targeted therapy.”

Editor’s note: A surgical biopsy (removal of a small sample of a tumor) can be used by a doctor to figure out if a patient’s tumor has certain genetic mutations. A tumor’s genetic mutations can help determine which treatments are most likely to work. Some doctors are reluctant to take surgical biopsies from patients with late-stage non-small cell lung cancer (NSCLC) because of concerns that dangerous complications will arise. But a new study found that, with careful expert review and good surgical approaches, certain late-stage patients can safely have surgical biopsies.

Few Circulating Cancer Cells Could Cue Risk of Metastases

“A simple noninvasive blood test matched with state-of-the-art molecular imaging of individual cells could help oncologists understand their patients’ chances of survival, say researchers. Metastasis accounts for an estimated 90 percent of cancer deaths. For decades, researchers tried to develop a way to gauge a cancer’s risk of metastasizing from a blood sample — the long-sought-after liquid biopsy.”

Few Circulating Cancer Cells Could Cue Risk of Metastases

“A simple noninvasive blood test matched with state-of-the-art molecular imaging of individual cells could help oncologists understand their patients’ chances of survival, say researchers. Metastasis accounts for an estimated 90 percent of cancer deaths. For decades, researchers tried to develop a way to gauge a cancer’s risk of metastasizing from a blood sample — the long-sought-after liquid biopsy.”