Robert L. Waterhouse Jr, MD, MBA
A new test that can detect the existence of tumor activity is gaining credibility as a means of confirming the results of prostate biopsies, which have the potential to miss tumor cells. The ConfirmMDx epigenetic assay from MDxHealth, of Belgium, hunts for signs of DNA methylation, and recent study results have confirmed its value. One study in particular, involving African American men, was presented in May at the American Urological Association (AUA) annual meeting and demonstrated strong negative predictive value.1
Prostate biopsies not only are invasive and uncomfortable for patients, but also carry significant risk for patients, who may suffer bleeding, pain, difficult or painful urination, and infection and may have blood in the urine or semen.2
These factors can make it challenging for urologists and patients to decide whether a second prostate biopsy is necessary if the initial test is inconclusive.
Further, prostate biopsies sometimes produce false-negative results due to the limitations of the current standard of care—a 12-core needle transrectal ultrasound-guided biopsy. “The challenge is that it is a relatively random sampling because although they’re trying to sample 12 definitive areas of the prostate, the needle may not always end up where it’s supposed to be,” explained Christopher Thibodeau, chief operating officer and EVP of MDxHealth, in an interview with OncologyLive ®
Although the biopsy is targeted for areas of most probable activity, it can still amount to a proverbial shot in the dark. “We’re sampling less than 1% of the prostate, so when we look at the men who are undergoing biopsies, most urologists would argue that there is a chance the biopsy might have missed something,” Thibodeau said.
The ConfirmMDx assay is efficient in that it can analyze the same tissue removed during a biopsy and potentially detect cancer even if tumor cells are not present in the sample. Typically, if after a prostate biopsy, a urologist still feels that the patient may be at risk for cancer—for example, based on results of a digital rectal exam or prostate-specific antigen (PSA) test—a second biopsy and perhaps even more could be performed. However, additional biopsies could compound the risk of bleeding and infection, lengthen recovery time for the patient, and cause patients to become frustrated with the process.
ConfirmMDx is an alternative to a string of repeat biopsies and their associated risks. “Around the area where the cancer cells are, there are changes happening,” said Wim Van Criekinge, PhD, chief scientific officer of MDxHealth and a professor at the University at Ghent in Belgium. “One of these changes is the DNA gets modified by being near the cancer cells. The cells containing that modified DNA have not [yet] become cancer cells themselves—that’s why the biopsy doesn’t recognize them as being abnormal. The molecular test can see the changes before they progress to a morphological level.”
Specifically, ConfirmMDx tests for methylation of the APC
, and RASSF1
genes, which are widely studied prostate cancer biomarkers that give an indication not only of the presence of cancer, but the aggressiveness of that cancer as well. Demonstrating confidence in the assay, the National Comprehensive Cancer Network (NCCN) this year recommended ConfirmMDx as a tool for early detection of prostate cancer. An NCCN panel stated that the assay “can be considered an option for men contemplating repeat biopsy because the assay may identify individuals at higher risk of prostate cancer diagnosis on repeat biopsy.”3
Specifically, the NCCN guidelines recommend the test for patients who have had at least 1 prior negative biopsy and are thought to be at higher risk, particularly when assessing their PSA levels. Other options listed for patients with a prior negative biopsy are percent- free PSA, the Prostate Health Index, the 4Kscore test, and a prostate cancer antigen 3 (PCA3) test.3
Improving Diagnosis in African American Men
The recent trial results showing that ConfirmMDx has predictive value among African American men suggest the potential for improved treatment in this population, which is underserved when it comes to prostate cancer diagnosis and therapy. African American males have a greater risk of clinically significant prostate cancer than the general population, and prostate cancer in this racial grouping tends to have a different molecular structure. They are approximately 1.6 times more likely than Caucasians and 2.7 times more likely than Asian Americans to develop the disease.4