Comparison among different precursor prostatespecific antigen isoform derivatives on prostate cancer prediction in patients with serum prostatespecific antigen bellow 10 ng/ml

Introduction/Objective. The precursor prostate-specific antigen (proPSA) especially its isoform p2PSA is useful in the detection of prostate cancer (PCa). However, the prediction value of different p2PSA derivatives remains unclear. The aim of the study was to compare the performance of the p2PSA, percentage of p2PSA to free PSA (%p2PSA), prostate health index (Phi), and one prostate dimension-adjusted index, p2PSA density (p2PSAD), with each other for PCa prediction in patients with serum PSA 10 ng/ml or less. Methods. This prospective study included patients who had undergone ultrasound-guided prostate biopsies and p2PSA testing. The data about patients? clinicopathological characteristics were collected and %p2PSA, p2PSAD and Phi were calculated. Different aspect of predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), the specificities at set sensitivities, and clinical utility using decision curve analyses (DCA). Results. PCa was diagnosed in 23 (32.4%) out of 71 patients. Results of multivariate analysis showed that only the Phi and digital rectal examination were independent predictors of PCa. The AUC of p2PSA, %p2PSA, p2PSAD and Phi were 76.2%, 81.5%, 88.7%, 89.6%, respectively. At pre-specified sensitivity of 90% and 95%, Phi demonstrated a greater specificity than the other p2PSA derivatives. Phi and p2PSAD lead to the higher net benefit in DCA. Conclusion. Compared with other p2PSA derivatives Phi is the most useful parameter for selection of the patients that do not need to be undergone to biopsy and thereby avoiding unnecessary procedures.

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PHI density prospectively improves prostate cancer detection

World Journal of Urology ◽

10.1007/s00345-020-03585-2 ◽

2021 ◽

Author(s):

Carsten Stephan ◽

Klaus Jung ◽

Michael Lein ◽

Hannah Rochow ◽

Frank Friedersdorff ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Roc Curves ◽

Grey Zone ◽

Net Benefit ◽

Threshold Probability ◽

Free Psa ◽

Prostate Health Index ◽

Magnetic Resonance Imaging Mri ◽

Prostate Health

Abstract Purpose To evaluate the Prostate Health Index (PHI) density (PHID) in direct comparison with PHI in a prospective large cohort. Methods PHID values were calculated from prostate-specific antigen (PSA), free PSA and [− 2]proPSA and prostate volume. The 1057 patients included 552 men with prostate cancer (PCa) and 505 with no evidence of malignancy (NEM). In detail, 562 patients were biopsied at the Charité Hospital Berlin and 495 patients at the Sana Hospital Offenbach. All patients received systematic or magnetic resonance imaging (MRI)/ultrasound fusion-guided biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing areas under the ROC-curves (AUC). The decision curve analysis (DCA) was performed with the MATLAB Neural Network Toolbox. Results PHID provided a significant larger AUC than PHI (0.835 vs. 0.801; p = 0.0013) in our prospective cohort of 1057 men from 2 centers. The DCA had a maximum net benefit of ~ 5% for PHID vs. PHI between 35 and 65% threshold probability. In those 698 men within the WHO-calibrated PSA grey-zone up to 8 ng/ml, PHID was also significantly better than PHI (AUC 0.819 vs. 0.789; p = 0.0219). But PHID was not different from PHI in the detection of significant PCa. Conclusions Based on ROC analysis and DCA, PHID had an advantage in comparison with PHI alone to detect any PCa but PHI and PHID performed equal in detecting significant PCa.

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Comparison of PHI and PHI Density for Prostate Cancer Detection in a Large Retrospective Caucasian Cohort

Urologia Internationalis ◽

10.1159/000517891 ◽

2021 ◽

pp. 1-6

Author(s):

Robert Peters ◽

Carsten Stephan ◽

Klaus Jung ◽

Michael Lein ◽

Frank Friedersdorff ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Volume ◽

Specific Antigen ◽

Roc Curves ◽

Net Benefit ◽

Threshold Probability ◽

Free Psa ◽

Prostate Health Index ◽

Caucasian Cohort ◽

Prostate Health

Background: Beyond prostate-specific antigen (PSA), other biomarkers for prostate cancer (PCa) detection are available and need to be evaluated for clinical routine. Objective: The aim of the study was to evaluate the Prostate Health Index (PHI) density (PHID) in comparison with PHI in a large Caucasian group >1,000 men. Methods: PHID values were used from available patient data with PSA, free PSA, and [−2]proPSA and prostate volume from 3 former surveys from 2002 to 2014. Those 1,446 patients from a single-center cohort included 701 men with PCa and 745 with no PCa. All patients received initial or repeat biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing area under the ROC curves (AUCs), precision-recall approach, and decision curve analysis (DCA). Results: PHID medians differed almost 2-fold between PCa (1.12) and no PCa (0.62) in comparison to PHI (48.6 vs. 33; p always <0.0001). However, PHID and PHI were equal regarding the AUC (0.737 vs. 0.749; p = 0.226), and the curves of the precision-recall analysis also overlapped in the sensitivity range between 70 and 100%. DCA had a maximum net benefit of only ∼5% for PHID versus PHI between 45 and 55% threshold probability. Contrary, in the 689 men with a prostate volume ≤40 cm3, PHI (AUC 0.732) showed a significant larger AUC than PHID (AUC 0.69, p = 0.014). Conclusions: Based on DCA, PHID had only a small advantage in comparison with PHI alone, while ROC analysis and precision-recall analysis showed similar results. In smaller prostates, PHI even outperformed PHID. The increment for PHID in this large Caucasian cohort is too small to justify a routine clinical use.

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External validation of prostate health index-based nomogram for predicting prostate cancer at extended biopsy

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh181226107s ◽

2020 ◽

Vol 148 (5-6) ◽

pp. 292-298

Author(s):

Milorad Stojadinovic ◽

Damnjan Pantic ◽

Miroslav Stojadinovic

Keyword(s):

Prostate Cancer ◽

Predictive Accuracy ◽

Characteristic Curve ◽

External Validation ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Validation Dataset ◽

Health Index ◽

Prostate Health Index ◽

Prostate Health

Introduction/Objective. Prostate Health Index (PHI)-based nomograms were created by Lughezzani et al. (2012) and Zhu et al. (2015) for predicting prostate cancer (PCa) at extended biopsy. The aim of the study was to externally validate two nomograms in the Serbian population. Methods. This retrospective study comprised 71 patients irrespective of digital rectal examination (DRE) findings, with prostate-specific antigen level < 10 ng/ml, who had undergone prostate biopsies, and PHI testing. Data were collected in accordance with previous nomograms predictors. Independent predictors were identified by using logistic regression. The predictive accuracy was measured by the area under the receiver operating characteristic curve (AUC). The calibration belt was used to assess model calibration. The clinical utility was measured by using decision curve analysis (DCA). Results. There were numerous differences in underlying risk factors between validation dataset and previously available data. Analysis demonstrated that the DRE and PHI were independent predictors. AUCs for both nomograms, in patients with normal DRE had shown to have a good discriminatory ability (77.2?86.2%). In the entire population AUC of nomogram had exceptional discrimination (92.9%). Zhu et al. nomogram is associated with lower false positive predictions. The calibration belt for Zhu et al. nomogram was acceptable. Our DCA suggested that both nomograms are likely to be clinically useful. Conclusion. We performed external validation of two PHI-based nomograms predicting the presence of PCa in both the initial and the repeat biopsy setting. The PHI-based nomograms displayed adequate accuracy and justifies its use in Serbian patients.

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

Clinical Chemistry ◽

10.1373/clinchem.2012.195784 ◽

2013 ◽

Vol 59 (1) ◽

pp. 306-314 ◽

Cited By ~ 75

Author(s):

Carsten Stephan ◽

Sébastien Vincendeau ◽

Alain Houlgatte ◽

Henning Cammann ◽

Klaus Jung ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Multicenter Study ◽

Clinical Performance ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Prostate Health

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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Analysis of risk factors for determining the need for prostate biopsy in patients with negative MRI

Scientific Reports ◽

10.1038/s41598-021-83802-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Linghui Liang ◽

Feng Qi ◽

Yifei Cheng ◽

Lei Zhang ◽

Dongliang Cao ◽

...

Keyword(s):

Prostate Cancer ◽

Detection Efficiency ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Multivariable Logistic Regression Analysis ◽

Detection Rates ◽

Prostate Biopsies ◽

Clinically Significant ◽

Definition Of ◽

Medical University

AbstractTo analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn’t need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.

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Usefulness of the prostate health index in predicting the presence and aggressiveness of prostate cancer among Korean men: a prospective observational study

BMC Urology ◽

10.1186/s12894-021-00897-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jae Yoon Kim ◽

Ji Hyeong Yu ◽

Luck Hee Sung ◽

Dae Yeon Cho ◽

Hyun-Jung Kim ◽

...

Keyword(s):

Prostate Cancer ◽

Observational Study ◽

Prospective Observational Study ◽

Specific Antigen ◽

Significant Proportion ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Total Psa ◽

Prostate Health

Abstract Background We aimed to evaluate the usefulness of the Beckman Coulter prostate health index (PHI) and to compare it with total prostate-specific antigen (PSA) levels and related derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in the Korean population. Methods A total of 140 men who underwent their first prostate biopsy for suspected PCa were included in this prospective observational study. The diagnostic performance of total PSA, free PSA, %free PSA, [–2] proPSA (p2PSA), %p2PSA, and PHI in detecting and predicting the aggressiveness of PCa was estimated using the receiver operating characteristic curve (ROC) and logistic multivariate regression analyses. Results Of 140 patients, PCa was detected in 63 (45%) of participants, and 48 (76.2%) of them had significant cancer with a Gleason score (GS) ≥ 7. In the whole group, the area under the curve (AUC) for ROC analysis of tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.63, 0.57, 0.69, 0.69, 0.72, and 0.76, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p = 0.005). For PCa with GS ≥ 7, the AUCs for tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.62, 0.58, 0.41, 0.79, 0.86, and 0.87, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p < 0.001). In the subgroup with tPSA 4–10 ng/mL, both %p2PSA and PHI were strong independent predictors for PCa (p = 0.007, p = 0.006) and significantly improved the predictive accuracy of a base multivariable model, including age, tPSA, fPSA and %fPSA, using multivariate logistic regression analysis. (p = 0.054, p = 0.048). Additionally, at a cutoff PHI value > 33.4, 22.9% (32/140) of biopsies could be avoided without missing any cases of aggressive cancer. Conclusions This study shows that %p2PSA and PHI are superior to total PSA and %fPSA in predicting the presence and aggressiveness (GS ≥ 7) of PCa among Korean men. Using PHI, a significant proportion of unnecessary biopsies can be avoided.

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Discordant prostate specific antigen test results despite WHO assay standardization

The International Journal of Biological Markers ◽

10.1177/1724600818754750 ◽

2018 ◽

Vol 33 (3) ◽

pp. 275-282 ◽

Cited By ~ 2

Author(s):

Martin Boegemann ◽

Christian Arsov ◽

Boris Hadaschik ◽

Kathleen Herkommer ◽

Florian Imkamp ◽

...

Keyword(s):

Prostate Cancer ◽

Early Detection ◽

Specific Antigen ◽

Test Results ◽

Serum Samples ◽

Prostate Specific Antigen Test ◽

Free Psa ◽

Prostate Biopsies ◽

Cancer Early Detection ◽

Total Psa

Introduction: Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Methods: Within the scope of the Prostate Cancer Early Detection Study Based on a ‘‘Baseline’’ PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing–Bablok regression method. Results: Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%–20%, and +17%–23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%–31%, and +22%, respectively. Discussion: Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.

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A urine exosomal circRNA classifier for detection of high-grade prostate cancer at initial biopsy: A multicenter, retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5522 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5522-5522

Author(s):

Liaoyuan Li ◽

Wen Tao ◽

Yadi He ◽

Tao He ◽

Qing Li ◽

...

Keyword(s):

Prostate Cancer ◽

Validation Cohort ◽

Characteristic Curve ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Circular Rna ◽

High Grade ◽

Training Cohort ◽

Potential Biomarker ◽

Initial Biopsy

5522 Background: The low specificity of prostate-specific antigen (PSA) has resulted in the overdiagnosis and overtreatment of clinically indolent prostate cancer (PCa). We aimed to identify a urine exosomal circular RNA (circRNA) classifier that could detect high-grade (Gleason score [GS]7 or greater) PCa. Methods: We did a three-stage study that enrolled eligible participants, including PCa-free men, 45 years or older, scheduled for an initial prostate biopsy due to suspicious digital rectal examination findings and/or PSA levels (limit range, 2.0-20.0 ng/mL), from four hospitals in China. We used RNA sequencing and digital droplet polymerase chain reaction to identify 18 candidate urine exosomal circRNAs that were increased in 11 patients with high-grade PCa compared with 11 case-matched patients with benign prostatic hyperplasia. Using a training cohort of eligible participants, we built a urine exosomal circRNA classifier (Ccirc) to detect high-grade PCa. We then evaluated the classifier in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy in two independent cohorts. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared Ccirc with standard of care (SOC) (ie, PSA level, age, race, and family history). Results: Between June 1, 2016, and July 31, 2019, we recruited 356 participants to the training cohort, and 442 and 325 participants to the two independent validation cohorts. We identified a Ccirc containing five differentially expressed circRNAs (circ_0049335, circ_0056536, circ_0004028, circ_0008475, and circ_0126027) that could detect high-grade PCa. Ccirc showed higher accuracy than SOC to distinguish individuals with high-grade PCa from controls in both the training cohort and the validation cohorts. (AUC 0.831 [95% CI 0.765-0.883] vs 0.724 [0.705-0.852], P = 0.032 in the training cohort; 0.823 [0.762-0.871] vs 0.706 [0.649-0.762], P = 0.007 in validation cohort 1; and 0.878 [0.802-0.943] vs 0.785 [0.701-0.890], P = 0.021 for validation cohort 2). In all three cohorts, Ccirc had higher sensitivity (range 71.6-87.2%) and specificity (82.3-90.7%) than did SOC (sensitivity, 42.3-68.2%; specificity, 40.1-62.3%) to detect high-grade PCa. Using a predefined cut point, 202 of 767 (26.3%) biopsies would have been avoided, missing only 6% of patients with dominant pattern 4 high-risk GS 7 disease. Conclusions: Ccirc is a potential biomarker for high-grade PCa among suspicious men.

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