Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; A, Marino; Sorrentino, Alessandra; Carlo, Angelina Di; Autorino, Riccardo; Lorenzo, Giuseppe Di; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

doi:10.1016/j.cca.2012.04.017

Cited by 51 publications

(35 citation statements)

References 34 publications

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“…Recently, %[Ϫ2]proPSA and Phi have also been successfully tested in repeat biopsy patients, but in contrast with our study, data on %[Ϫ2]proPSA were better than on Phi (37 ). During the preparation of this manuscript, a report of a study with combined data on Phi and PCA3 in 151 patients was published (22 ). Data on urinary PCA3 and T2:ERG were available from a small cohort of 78 men (19 ).…”

Section: Discussioncontrasting

confidence: 62%

“…Ferro et al (22 ) stated that multivariable analysis produced no significant model to improve the performance of their single biomarkers. Inclusion of all factors such as age, DRE status, prostate volume, PSA, %fPSA, or T2:ERG did not improve the AUC over the simple model with PCA3 and Phi only.…”

Section: Discussionmentioning

confidence: 99%

“…Investigations with data on Phi and PCA3 (22 ) or PCA3 and T2:ERG have been performed (20,23 ), but a comparison of all 3 biomarkers in the same population has not been conducted so far. Therefore the aims of this study were to compare the clinical validity of Phi, PCA3, and T2:ERG in general and in different subpopulations of men who had undergone initial and repeated biopsies and to evaluate the diagnostic power of these biomarkers within a multivariate model.…”

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confidence: 99%

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Comparative Assessment of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG Gene Fusion with the Serum [−2]Proprostate-Specific Antigen–Based Prostate Health Index for Detection of Prostate Cancer

Stephan

Jung

Semjonow³

et al. 2013

Clinical Chemistry

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BACKGROUND We compared urinary prostate cancer antigen 3 (PCA3), transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG), and the serum [−2]proprostate-specific antigen ([−2]proPSA)-based prostate health index (Phi) for predicting biopsy outcome. METHODS Serum samples and first-catch urine samples were collected after digital rectal examination (DRE) from consented outpatients with PSA 0.5–20 μg/L who were scheduled for prostate biopsy. The PCA3 score (PROGENSA PCA3, Hologic Gen-Probe) and T2:ERG score (Hologic Gen-Probe) were determined. Measurements of serum PSA, free PSA, and [−2]proPSA (Beckman Coulter) were performed, and the percentages of free PSA (%fPSA) and Phi ([−2]proPSA/fPSA × √PSA) were determined. RESULTS Of 246 enrolled men, prostate cancer (PCa) was diagnosed in 110 (45%) and there was no evidence of malignancy (NEM) in 136 (55%). A first set of biopsies was performed in 136 (55%) of all men, and 110 (45%) had ≥1 repeat biopsies. PCA3, Phi, and T2:ERG differed significantly between men with PCa and NEM, and these markers showed the largest areas under the ROC curve (AUCs) (0.74, 0.68, and 0.63, respectively). PCA3 had the largest AUC of all parameters, albeit not statistically different from Phi. Phi showed somewhat lower specificities than PCA3 at 90% sensitivity. Combination of both markers enhanced diagnostic power with modest AUC gains of 0.01–0.04. Although PCA3 had the highest AUC in the repeat-biopsy cohort, the highest AUC for Phi was observed in DRE-negative patients with PSA in the 2–10 μg/L range. CONCLUSIONS PCA3 and Phi were superior to the other evaluated parameters but their combination gave only moderate enhancements in diagnostic accuracy for PCa at first or repeat prostate biopsy.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Comparative Assessment of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG Gene Fusion with the Serum [−2]Proprostate-Specific Antigen–Based Prostate Health Index for Detection of Prostate Cancer

Stephan

Jung

Semjonow³

et al. 2013

Clinical Chemistry

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“…A recent comparison of Phi with another promising PCa biomarker, PCA3, revealed a larger AUC for Phi compared with PCA3, but the difference was not statistically significant (38 ). In an analytical multicenter study by Sokoll et al (39 ), the p2PSA assay showed a clinically acceptable analytical performance with excellent precision and reproducibility and had negligible interference from other PSA isoforms.…”

Section: Multicenter Evaluation Of [؊2]proprostate-specific Antigenmentioning

confidence: 95%

Multicenter Evaluation of [−2]Proprostate-Specific Antigen and the Prostate Health Index for Detecting Prostate Cancer

et al. 2013

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BACKGROUND Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [−2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA × √tPSA, was evaluated in a multicenter study for detecting PCa. METHODS A total of 1362 patients from 4 different study sites who had tPSA values of 1.6–8.0 μg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score. CONCLUSIONS The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6–8.0 μg/L (i.e., approximately 2–10 μg/L in traditional calibration) and is better able to detect aggressive PCa.

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“…Nowadays many studies are researching the new tumor markers that was correlated to the diagnosis and prognosis of the prostatic carcinoma [11][12]. CEACAM5 is a tumor-associated antigen that plays an important regulatory role in cell adhesion and in tumor cell chemosensitivity [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

CEACAM5 is correlated with Angio/Lymphangiogenesis of Prostatic Lesions

et al. 2014

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Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers

Cited by 51 publications

References 34 publications

Comparative Assessment of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG Gene Fusion with the Serum [−2]Proprostate-Specific Antigen–Based Prostate Health Index for Detection of Prostate Cancer

Comparative Assessment of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG Gene Fusion with the Serum [−2]Proprostate-Specific Antigen–Based Prostate Health Index for Detection of Prostate Cancer

Multicenter Evaluation of [−2]Proprostate-Specific Antigen and the Prostate Health Index for Detecting Prostate Cancer

CEACAM5 is correlated with Angio/Lymphangiogenesis of Prostatic Lesions

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