%p2PSA and PHI may prove more accurate than tPSA, fPSA, and %fPSA in predicting prostate cancer in men with a positive family history, "Beyond the Abstract," by Alberto Abrate, MD, et al

BERKELEY, CA (UroToday.com) - The AUA Guidelines on Early Detection of Prostate Cancer suggest a PSA-based prostate cancer screening in men younger than 55 years of age with a positive family history. Indeed, a positive family history is associated with an approximately two-fold increased risk of prostate cancer diagnosis, and the risk increases according to the number of affected family members, their degree of relatedness, and the age at which they were affected. These data are even more important if we consider the incidence of prostate cancer. In fact, prostate cancer is the most common cancer in men, and every patient transmits a risk to his first-degree relatives. Thus prostate cancer needs to be considered an epidemic disease that must be addressed with care by physicians and urologists.

PSA is known to be affected by low specificity that limits its capacity to predict the presence of prostate cancer at biopsy; thus, still today, a high rate (60-65%) of biopsies are reported to be negative, and consequently unnecessary. [-2]proPSA (p2PSA) has recently emerged as a new biomarker, more specific for prostate cancer: also its derivatives, the percentage of p2PSA (%p2PSA) and the prostate health index (PHI), were proven to be useful. In particular PHI combines total serum PSA (tPSA), free PSA (fPSA) and p2PSA using the mathematical formula: (p2PSA ÷ fPSA) × √PSA. In many recent studies, p2PSA and PHI improved specificity for prostate cancer detection compared with PSA and percent free PSA (%fPSA). That's why we hypothesised that p2PSA and its derivatives (for their clinical utility) could play a role for screening in a non-affected population but with a positive family history.

In this study, we considered 158 patients from a European multicenter project, all with a first-degree relative (father, brother, son) diagnosed with prostate cancer. Similar to previous studies of a general population of men, we found that %p2PSA and PHI outperformed PSA (and derivatives) for prostate cancer detection, avoiding several unnecessary biopsies and missing only few low-grade prostate cancers.

Our study has a number of strengths: it has a multi-institutional design, its diagnostic procedures were strictly protocolled, and it appears to be the first study in which p2PSA and its derivatives (percentage of p2PSA [%p2PSA], and PHI) were prospectively evaluated in a group of patients with positive family history of prostate cancer. However, our study has also some limitations: all men were European with unclear generalizability to other ethnic groups, the small sample size precluded the evaluation of subsets of patients based on total PSA levels or other risk factors, and patients were included in the study for their risk of prostate cancer and not primarily for their family history.

In conclusion, our findings support the hypothesis that %p2PSA and PHI are more accurate than tPSA, fPSA, and %fPSA in predicting prostate cancer in men with a positive family history. Thus, considering %p2PSA and PHI may help physicians in clinical decision making to avoid several unnecessary biopsies.

Written by:
Alberto Abrate, Massimo Lazzeri, and Giorgio Guazzoni as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Dept. of Urology, Ospedale San Raffaele Turro, San Raffaele Scientific Institute, Milan, Italy

Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: Results from a multicentre European study, the PROMEtheuS project - Abstract

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