Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

Abstract

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA.

The percentage of prostate‐specific antigen (PSA) isoform [–2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years

“…Within this range, more unnecessary biopsies can be spared compared with standard testing. These results have recently been supported by the DCA on a large ageindependent cohort with initial biopsies by Lazzeri et al [39] and Ferro et al [40].…”

Comparative analysis of the PCA3 gene expression in sediments and exosomes isolated from urine

“…В ис-следованной выборке было 5 образцов в «серой зоне» ПСА они были корректно классифицированы при уста-новленных на предыдущем этапе ROC-анализа опти-мальных пороговых уровнях 1,86 и 1,48 для осадков и экзосом мочи соответственно (за исключением 1 ложноположительного случая при анализе экзосом). Это согласуется с тем, что PCA3 охарактеризован рядом авторов как маркер с диагностической точностью вы-ше, чем у общего и отношения свободного к общему ПСА, особенно в «серой зоне» 2-10 нг/мл [17,18], в том числе и при первичной диагностике РПЖ [19,20]. Вме-сте с тем необходимо иметь в виду малый объем выбор-ки и наличие «серой зоны» deltaCt, описанной нами ранее при анализе экспрессии РСА3 в РПЖ [16].…”

A novel NMF-based DWI CAD framework for prostate cancer.

“…A similar study was performed by Catalona et al [17], which found that diagnosing using %fPSA had an AUC of 0.525, using fPSA had an AUC of 0.615, using p2PSA had an AUC of 0.557, 6 and using PHI had an AUC of 0.703 for 1,372 subjects. Additionally, Ferro et al [28] found that fPSA had an AUC of 0.60, %fPSA had an AUC of 0.62, %p2PSA had an AUC of 0.76, and PHI had an AUC of 0.77 for 300 subjects.…”

“…A common urine-based biomarker is PCA3 (formerly DD3), a prostate specific non-coding RNA [29,30,32,36]. The reported studies [20,21,25,28,[37][38][39] showed an AUC ranging from 0.64-0.74 for PCA3. Hessel et al…”

“…Roobol et al [21] also tested PSA and PCA3 biomarkers for 7 721 subjects and found an AUC of 0.58 for PSA-based tests and an AUC of 0.64 for PCA3-based tests. In addition, Ferro et al [28] performed a PCA3 study that resulted in an AUC of 0.73 for 300 subjects.…”