By Jeffrey Turner, MD
Clinically Significant Prostate Cancer
The United States Preventive Services Task Force advised against routine PSA screening claiming the risks outweigh the benefits given that overtreatment of indolent (low-grade) prostate cancer has become an epidemic. But there is a problem: Without screening and early detection for the 20-30% of men that are diagnosed with a higher grade type prostate cancer, they lose their chance to be cured. Therefore, there is an unmet need for noninvasive tests which would help us accurately differentiate low-grade (Gleason 6) from higher-grade prostate cancer. (Gleason 7 or higher).
The OPKO 4Kscore blood test predicts one’s risk of having Gleason ≥ 7 on a future prostate biopsy. The assay measures several blood enzymes including total PSA, free PSA, intact PSA, and human kallikrein 2. The backbone of this test are four-kallikrein biomarkers which more accurately detect the aggressive and more lethal forms of cancer. The test reports the likelihood of higher grade cancer as a range from <1% to >95%. When the OPKO 4Kscore is under 7.5% a man can be fairly sure that no high-grade tumor is present. Studies show that men who use the 4Kscore test undergo 56% fewer biopsies and only 1 out of 40 men with higher-grade disease would have a delayed diagnosis.
Also, 4Kscore has potential utility for staging men with prostate cancer that have already been diagnosed. For example, in one study, men with a 4Kscore over 20% had tumor upgrading 85% of the time, even when the initial Gleason score was 6. Men with higher 4Kscore results were not only found to have higher grade cancers, but also a higher evidence of extracapsular extension1 (spread outside the prostate).
ExoDx Prostate (IntelliScore)
The ExoDx Prostate (IntelliScore) is a first-catch urine test which does not require a digital rectal examination (DRE) like the old PCA-3 urine test. The ExoDX analyzes for several tumor-specific genes ERG, PCA3, and SPDEF.2 Statistics show that this test is over 90% accurate, which is a vast improvement over PSA. In a study of 1,000 patients the test only failed to detect Gleason 7 cancers in 12 out of 148 men. And of those 12 patients only 3 (5%) had a dominant pattern 4, the type of cancer that needs to be detected.
Up until now we have been required to depend on imaging and biopsy to rule out clinically-significant prostate cancer in men who have a high PSA. Today, there are more and more ways to evaluate men who run high men with elevated PSA levels. Coupling noninvasive tests such as OPKO 4Kscore and ExoDx with modern imaging such as 3T multi-parametric MRI greatly increases our ability to avoid unnecessary biopsy in men whose PSA levels are elevated.
1. Punnen, Sanoj et al. The 4Kscore Predicts the Grade and Stage of Prostate Cancer in the Radical Prostatectomy Specimen: Results from a Multi-Institutional Prospective Trial. European Oncology. January 2016.
2. McKiernan, James et al. A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate cancer at Initial Biopsy. JAMA Oncology. March 2016.