THE "NEW" PROSTATE CANCER INFOLINK

The precise ability of the various genetic/genomic tests now available to accurately analyze the risk for clinically significant prostate cancer based on biopsy tissue samples is an important factor that all of the different developers and manufacturers of these tests continue to study in greater detail.

These tests include:

• The Prolaris test, from Myriad Genetics
• The Oncotype DX Prostate Cancer Assay from Genomic Health
• The Confirm MDx test for prostate cancer from MDxHealth
• The ProstaVysion test from Bostwick Laboratories

Each of these tests assesses the presence or absence of a differing but specific set of genes that are known to be associated with risk for prostate cancer in tissues extracted by a prostate biopsy, and they use data from these assessments to provide the patient and his doctors with a “risk score” of some type that may be helpful in deciding whether a patient does or does not necessarily require early treatment (as opposed to being monitored on active surveillance).

So one of the key questions about all of these tests is the degree to which the risk scores provided correlate with the data on which we have historically been dependent (PSA level, clinical stage, Gleason score, tumor volume, PSA density, etc.).

Data presented the other day at a meeting of the Urological Research section of the European Association of Urology in Glasgow, Scotland, have provided us with some new insight into this topic for one of these tests — the Confirm MDx test — that we shall describe below. However, we hasten to emphasize that (as far as we are aware) there has been no comparative analysis of the accuracy of any one of these genetic/genomioc tests to any other, and we therefore have no idea which of these various tests might be the most accurate in providing a risk score for clinical significance of prostate cancer based on biopsy tissue.

Based on data provided in a media release from MDxHealth, these were the findings of a study presented by Van Neste et al.:

• Hypermethylation levels of the GSTP1, APC and RASSF1 genes were evaluated.
• Biopsies were carried out on all test subjects using a standard 12-core systematic biopsy.
• Biopsy specimens were available from 102 men with a range of clinical risk profiles.
• 82/102 men were diagnosed with prostate cancer based on their biopsy results.
  • These men’s Gleason scores ranged from 3 + 3 = 6 to 4 + 4 = 8.
  • These men’s NCCN risk profiles (similar to the D’Amico risk profiles) ranged from very low to high.
• Biopsy specimens were also available from an additional 20 “control” patients who had not been found to have an prostate cancer.
• There were no epigenetic aberrations for any of the three Confirm MDx genes in any of the 20 control patients.
• Among 46 men with prostate cancer but a Gleason of 6 or less who met criteria for management on active surveillance,
  • 38 (83 percent) exhibited an epigentic profile that confirmed their appropriateness as candidates for active surveillance.
  • 8 (17 percent) exhibited an epigenetic profile suggestive of higher-grade disease who were therefore considered not such good canadiates for active surveillance.
• 8/9 men (88 percent) with prostate cancer and a Gleason score of 4 + 3 = 7 or higher exhibited many epigenetic aberrations.
• 17/27 men (63 percent) with prostate cancer and a Gleason score of 3 + 4 = 7 exhibited epigenetic aberrations.
• 31/39 men (79 percent) with intermediate- or high-risk disease based on NCCN criteria showed similar epigenetic profiles to those for patients witgh Gleason scores of 7 or higher.
• Roughly one-third of the patients in the very low- and low-risk NCCN categories showed similar epigenetic profiles to the men with Gleason scores of 6 or less.

So what does a study like this actually tell us?

First, it does tell us that there is a significant degree of correlation between Gleason scores and the epigenetic profile of the patients and between the NCCN risk criteria and the epigenetic profiles. However, this correlation is not perfect.

Second, it tells us that about 20 percent of men who meet NCCN criteria for active surveillance have an aberrant epigenetic profile suggestive of the fact that they may, in fact, need early treatment. … But it can not tell us that early treatment is absolutely essential. It may only be a good indicator that such men need to be monitored swith particular care on active surveillance because they are at higher than average risk for progression.

Third, it tells us that about 40 percent of men with Gleason 3 + 4 = 7 disease have no epigenetic risk factors based on these specific genes, and that these patients may, therefore, be appropriate candidates for active surveillance (but again, we cannot be certain, and if active surveillance was implemented in such patients, they would again need to be followed with great care).

Finally, it tells us that most men with Gleason 4 + 3 = 7 disease do have abberrant epigentic profiles and that these men are probably rarely going to be appropriate candidates for active surveillance (and this is hardly a surprise).

The “New” Prostate Cancer InfoLink does feel that a test like the Confirm MDx test for prostate cancer can be helpful in helping a man with very low-, low-, or intermediate-risk prostate cancer make the decision whether active surveillance is an appropriate management strategy (so long as his Gleason score is 3 + 4 = 7 of lower).  But … whether this test is any better than any other genetic/genomic tests for risk of clinically significant disease is still one of the great unknowns.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk | Tagged: clinical, genetic, genomic, risk, significance, test |