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MRI vs. PSA / 4Kscore® – Smarter prostate cancer screening

While prostate cancer is the most frequently diagnosed cancer in men in the United States, death rates have been steadily declining since the 1990s due to the implementation of early screening protocols.1 The current standard involves a test for the presence of prostate-specific antigen (PSA) in the blood, often following a digital rectal exam (DRE) – a manual search for abnormal lesions on the prostate. Men presenting with elevated PSA levels above the clinically accepted “cut-off” value of 4.0 ng/mL (paired with or without an abnormal DRE) are generally advised to undergo prostate biopsies for confirmation of the presence or absence of cancer.

Although the PSA method has been successful in reducing the overall mortality of prostate cancer, it is notoriously unspecific – meaning that it often produces false positives for the presence of disease, resulting in many cases of unnecessary prostate biopsy.2,3 These biopsies are invasive, and can lead to complications such as bleeding, infection, pain, lower urinary tract symptoms, and erectile dysfunction.4,5 Moreover, the combined DRE + PSA screening modality has an unclear negative predictive value (the probability that a negative test result aligns with absence of disease), limiting the credibility of “low potential for prostate cancer” assessments.6 What, then, are the next steps in developing smarter prostate cancer screening techniques?

Two approaches have recently emerged that could greatly improve the future of prostate cancer screening. First, the proprietary 4Kscore® Test (OPKO Lab, Nashville, TN) is a blood panel that extends the standard PSA test by evaluating a number of additional prostate-specific markers. It has shown better diagnostic performance than PSA in detecting the presence of significant prostate cancer in subsets of individuals already pre-selected for biopsy.7–9 However, the reported accuracy of the technique is potentially inflated due to the targeted pre-selection of patients for the studies. An additional screening methodology is multi-parametric MRI (mpMRI), which, across a number of recent studies, demonstrated a higher predictive value in detecting prostate cancer than standard PSA screening in subsets of the general population.10–12 It was even shown to be the more valuable technique in overall risk-stratification of disease when both mpMRI and a 4Kscore® were used together.13

While the clinical utility of both approaches is obvious, using the 4Kscore® as an expansion of the standard PSA blood panel doesn’t appear to perform as well as mpMRI in improving screening outcomes. mpMRI not only offers improved generalized detection rates and risk-stratification than other screening modalities, it also has significant advantages over the PSA / 4Kscore® with regards to a subsequent biopsy, if one were to occur. Traditionally, urologists use transrectal ultrasound (TRUS) guided biopsies for definitive diagnostic purposes. However, recent studies have revealed that the TRUS method is prone to low initial biopsy yields (over 25% of prostate cancers are missed during the first biopsy) due to sampling error and technical limitations.15,16 The emergence of mpMRI for prostate cancer evaluation has led to the concomitant development of TRUS – MRI fusion biopsies, in which urologists use mpMRI images to more precisely target problem areas of the prostate. This has significantly improved the detection rates of high-grade aggressive prostate cancer and decreased the detection of non-clinically significant lesions, when compared to simple TRUS biopsies.17–19 In light of recent studies highlighting the superiority of MRI in both pre-biopsy risk stratification and biopsy detection outcomes relative to standard techniques, many universities now advise performing a mpMRI prior to undergoing biopsy, regardless of preexisting test results.20,21

In short, the scientific literature indicates that mpMRI has a proven track record in both better identifying prostate cancer and improving the accuracy of resultant biopsies than traditional methods (PSA screening) or improved biomarker panels (4Kscore®). As either a reflex test for at-risk individuals or as a general population screening technique, mpMRI has the potential to reduce the number of unnecessary prostate biopsies, and provide a better experience for those that occur.