Biomarkers are objective tools which guide our decision making, and they are indicators of normal or patologic biologic processes. The ideal biomarker is 100% effective, with a NPV of 100, cheap, and non-invasive. Biomarkers in blood (4K, PHI) urine (PCA3, SELECT MDX) and tissue have been developed.
4K score. It is a test which combines 4 prostate-specific kallikrein assay results (PSA, fPSA, intact PSA and HK2) with clinical information (age, previous biopsy and DRE) in an algorithm that calculates the individual patient’s percent risk for aggressive prostate cancer, Gleason 7 or more. Contraindications are: DRE in the previous 96 hrs, treatment with 5-a-reductase inhibitors, and histry of BPE surgery. In the initial 4K validation study, they detected 23% cases of Gleason 7 or more, the AUC was 0.82, with a reduction of 58% of negative biopsies, with few false positives. The results are given a s a percentage of probability of having a low, intermediate or high risk cancer. This will help us decide wether or not to biopsy our patient.
PHI. It is a mathematical model, a formula, given by total PSA, fPSA and another kallikrein. It calculates a number, which goes from 0- 100, the higher the number, the higher the risk of having cancer Gleason 7 or more. Having score over 28.6 will spare 30% of negative biopsies. It should be used in men over 50 years with normal DRE and a PSA in the gray area.
PCA3. It is a specific test for prostate cancer, a no codifing messenger RNA, which has been found to be elevated in 90% of cases with prostate cancer. The test is done in a urine sample, after a prostatic massage. The higher the results, the higher the risk of having cancer. A drawback of this test is that it doesn´t specify if it is more likely to have a low, intermediate or high risk cancer. A variation from PCA3 is the MIPs test, which adds another 3 biomarkers.
SELECT MDX. It is another diagnostic tool performed in a urine sample after a DRE. It measures mRNAs and combines clinical features into al algorithm. An advantage of this test is that it identifies gleason 7 or higher (intermediate-high risk).
CONFIRM MDX. It si an epigenetic test in tissue obtained from biopsies. It searches for metilation patterns in genes of the surrounding tissue of the biopsy. It is useful for confirmation of negative biopsies in patientes with a high clinical suspicion but with a negative biopsy, with an AUC of 0.74, NPV 96%. Its use can be limited by its high cost.
Biomarkers are useful tools that are already mentioned in international guidelines, although indications are not that clear. It is likely that they will be part of the diagnostic algorithm for prostate cancer in the near future.
Presented by: Daniel Olvera Posada, MD
Written by: Paulina Bueno Garcia Reyes, MD, medical writer for UroToday.com and Ashish Kamat, MD, Professor of Urology and Director of Urologic Oncology Fellowship at M.D. Anderson Cancer Center, at the Mexican Urologic Oncology Association Meeting - July 26 - 28, 2018