There are two basic “buckets” of biomarkers in the prostate cancer diagnosis space. The initial biopsy bucket includes PSA, %free PSA, SelectMDx, prostate health index (PHI), 4K score, and ExoDx. The negative prior biopsy bucket includes ConfirmMDx, SelectMDx, PHI, and 4k score.
The original serum biomarker was prostate specific antigen (PSA). Stamey’s work taught us to use a cut-off of 4ng/mL and Dr. Catalona redefined this suggesting that a cut-off of 2.5ng/mL ought to be used. Dr. Carter brought the concept of PSA velocity in which an increase of 0.75ng/mL was concerning and Dr. Benson popularized the concept of PSA density in which concern was defined as >0.15 PSA/gram of prostate tissue. Lastly, Partin and Catalona introduced percent-free PSA; here, < 10% is worrisome and > 25% is considered to represent benign elevation.
The PHI is calculated using the following equation: p2PSA/fPSA x square root of PSA. The probability of cancer increases with an increase in the PHI score. Specifically, a score of < 25 represents an 11% probability of cancer), scores of 25-34.9 represent 18%risk, scores of 35-54.0 harbor 33% risk, and > 55c confer 52% risk. The 4 Kallikrein score (4K) resulted in an 8-13% increase in predictive accuracy and reduced unnecessary biopsy from 48-56%. Further, the annual savings in the US because of this reduction in unnecessary biopsy has been estimated at $19 million to $1 billion. Current cost is approximately $395 out-of-pocket.
Urine biomarkers provide slightly different information from the serum-based tests. ExoDx is a non-DRE urine sample for men presenting for initial biopsy with PSA levels of 2-10ng/mL. The, ExoDx risk score is then used to predict the presence of high grade (7 or higher) prostate cancer. For high grade disease, an ExoDx risk cut off score of 15.6 provides a negative predictive value (NPV) 0.96 and positive predictive value (PPV) of 0.37. The PCA3 test requires an attentive prostate massage followed by a urine specimen. It provides the risk of having prostate cancer at the time of biopsy. There is a linear relationship between PCA3 score and positive future biopsy with a recommended cut-off value of 35. For men with PCA3 score greater than 60, the PPV is 0.8 (95% CI 0.72-0.86). For men with a PCA3 score less than 20, the NPV is 0.88 (95% CI 0.81-0.93). SelectMDx combines two homeobox genes (HoxC6 and DLX1). It provides a 98% NPV for high risk (Gleason sum 7 or higher) prostate cancer and a 99% NPV for Gleason sum 8 or higher.
Dr. Partin discussed one tissue-based test that can be used to determine whether someone would need a rebiopsy. He shared the strategy he uses in this regard. If the patient has a high risk initial biopsy (PSA > 1.5, HGPIN > 2 cores, ASAP, or atypia), he sends the ConfirmDx. If the result is negative, biomarkers (e.g. PSA) are followed and mpMRI is considered in the future. If positive. Dr. Partin recommends mpMRI with repeat biopsy within 1 year (+/- fusion).
To close, Dr. Partin offered brief comments on mpMRI for biopsy. He does not recommend mpMRI for the initial biopsy (in fact, may payers will not approve). He advised waiting 3-4 months after the initial biopsy to avoid artifact. PIRADS should be utilized and fusion biopsy for PIRADS 3-5 lesions. When using algorithms that specify number of core, positive cores taken from “target areas” should only be counted once. Lastly, the MRI should only be repeated every two years since the results tend not to change over short interval follow-up periods.
Presented by: Alan Partin, MD, PhD
Written By: Benjamin T. Ristau, MD, Fox Chase Cancer Center, Philadelphia, PA
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA