Diagnostic accuracy of [-2]proPSA versus Gleason score and Prostate Health Index versus Gleason score for the determination of aggressive prostate cancer: a systematic review.

Objective: The objective of this review was to determine the diagnostic accuracy of [-2]proPSA (p2PSA) and the Prostate Health Index compared to the Gleason score in determining the aggressiveness of prostate cancer.

Introduction: Prostate cancer is the most commonly diagnosed cancer in men. However, the utility of currently available biomarkers for determining the aggressive form of the disease remains unknown. This review sought to determine the diagnostic accuracy of two new biomarkers in determining the aggressive form of prostate cancer.

Inclusion Criteria: Diagnostic accuracy studies that enrolled men of any age and any prostate specific antigen (PSA) level with histologically confirmed prostate cancer in which Prostate Health Index and p2PSA were assessed in comparison to Gleason score for the determination of aggressive prostate cancer were considered for inclusion. There was no time limitation on study inclusion.

Methods: A three-step search strategy was utilized to identify both published and unpublished studies in the English language in the following sources: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, Google Scholar, MedNar, and SIGLE. Databases were searched from inception to January 2019. Study selection, critical appraisal, data extraction, and data synthesis were done according to the approach recommended by JBI.

Results: A total of 12 studies (n = 8462) that recruited men with aggressive prostate cancer were considered in this review. The majority of included subjects had a total PSA level of 2 to 10ng/mL. The sensitivity of the Prostate Health Index ranged from 67% to 97% while specificity ranged from 6% to 64%. At a Prostate Health Index threshold of 25 and below (three studies, n = 3222), pooled sensitivity was 97% (95% confidence interval [CI], 95% to 98%) and specificity was 10% (95% CI, 6% to 16%). At a Prostate Health Index threshold of between 26 and 35 (six studies, n = 6030), pooled sensitivity was 87% (95% CI, 8% to 91%) and specificity was 45% (95% CI, 39% to 50%). At a Prostate Health Index threshold of 36 and above (five studies, n = 1476), pooled sensitivity was 72% (95% CI, 64% to 79%) and specificity was 74% (95% CI, 68% to 80%). Only one study assessed p2PSA. Sensitivity ranged from 80% to 95%, and specificity ranged from 9.9% to 27.9% with increasing threshold values from 7.9 to 10.9ng/mL.

Conclusions: Overall, both Prostate Health Index and p2PSA have acceptable accuracy for the determination of the likelihood of aggressive prostate cancer. However, the inverse relationship between sensitivity and specificity makes it difficult to determine an optimum cut-off value for positivity. Further research is warranted to determine their utility in the management of prostate cancer.