Abstract:
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Methods: A three-step search strategy was utilized to identify both published and unpublished studies in the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 ¼ 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 ¼ 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 ¼ 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 ¼ 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.