Clinical performance of serum isoform [-2]proPSA (p2PSA) and its derivatives, namely %p2PSA and PHI (Prostate Health Index) in men younger than 60 years of age, "Beyond the Abstract," by Nicola Fossati, et al

BERKELEY, CA ( - Although there is controversy over the benefit of PSA screening, early detection of prostate cancer in young men could reduce cancer-specific mortality. [-2]proPSA (p2PSA) and Prostate Health Index (PHI) represent new promising biomarkers. Preliminary investigations and observational studies have shown that p2PSA, a serum isoform of PSA and its derivates, may help to discriminate between men with and without prostate cancer. To the best of our knowledge, there have been no published studies characterizing p2PSA and PHI in men younger than 60 years of age. To address this issue, we test the hypothesis that p2PSA and its derivates are more accurate than total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (%fPSA) in detecting cancer in young men.

Our analysis consisted of a nested case-control study from the PRO-psa Multicentric European Study (PROMEtheusS) project. The primary outcome was the measure of sensibility, specificity, and accuracy of serum p2PSA, percentage of p2PSA to fPSA (%p2PSA), and PHI in men younger than 60 years of age who had undergone prostatic biopsy for suspected prostate cancer. The potential reduction of unnecessary biopsies and the characteristics of missed cases of cancer were reported as secondary outcomes. Multivariable, logistic, regression models were complemented by predictive accuracy analysis and decision curve analysis.

Of the 1 036 patients enrolled in the PROMEtheusS cohort, 238 (23%) were younger than 60 years. Prostate cancer was found in 67 participants (28%), that showed p2PSA, %p2PSA, and PHI values significantly higher than cancer-free participants (p<0.0001); no differences were found for tPSA, fPSA, and %fPSA values. Univariate accuracy analysis revealed %p2PSA (AUC: 0.70) and PHI (AUC: 0.70) to be the most accurate cancer predictors, significantly outperforming tPSA (AUC: 0.55), fPSA (AUC: 0.51) and %fPSA (AUC: 0.56) (p≤0.001). In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models, including PSA and prostate volume, by 6% and 7%, respectively (p≤0.05).

In the current study, both %p2PSA and PHI showed significantly higher accuracy in predicting the presence of prostate cancer at biopsy when compared to tPSA, fPSA and %fPSA in a group of patients younger than 60 years of age. Specifically, in accuracy analyses, %p2PSA and PHI were 27% more accurate than tPSA in detecting patients with prostate cancer. Finally, decision curve analysis data suggested the highest net benefit might be gained in those challenging patients who have probability thresholds of about 50%.

In conclusion, our findings show that %p2PSA and PHI are more accurate than the reference standard tests (tPSA, fPSA and %fPSA) in predicting prostate cancer in men younger than 60 years of age and may also be indicative of cancer aggressiveness. These results should be taken into account when considering PCa screening studies in young patients.

Written by:
Nicola Fossati, Massimo Lazzeri, Alessandro Larcher, Nicolò Buffi, and Giorgio Guazzoni as part of Beyond the Abstract on 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.

Department of Urology, San Raffaele Turro Hospital, Milan, Italy

Clinical performance of serum isoform [-2]proPSA (p2PSA) and its derivatives, namely %p2PSA and PHI (Prostate Health Index) in men younger than 60 years of age: Results from a multicentric European study - Abstract

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