Current biomarkers of prostate cancer

Prostate cancer is one of the most common malignancies in men. Early detection of prostate cancer is largely determined by the widely used prostate specific antigen (PSA) blood test. However, as a diagnostic and prognostic test of prostate cancer, PSA has limited specificity, sensitivity and leads to hyper or underdiagnosis, which, in turn, can lead to excessive treatment. There fore, it is very important to develop diagnostic markers that can be used to determine prostate cancer at an early stage of development, assess the possible progression of the disease and prescribe optimal therapy. Significant progress has been made in the discovery of biomarkers for prostate cancer. For example, biomarkers such as %-free PSA, Prostate Health Index (PHI) or 4K score can be used to increase specificity and reduce the number of unnecessary biopsies, while the PCA3 test can be used to reduce the number of repeated biopsies in men with previously negative biopsy. To determine aggressiveness and predict the outcome of the disease, tissue multigenic tests can be used, such as: T2-ERG, ExoDx, SelectMDx and ConfirmMDx, Prolaris, Oncoytype DX, Decipher. The development of such diagnostic tests opens up new opportunities for improving the diagnosis of prostate cancer, prognosis and decision-making on the appointment of therapy. And with the increase in their availability, finally, the possibility of an individual approach to the appointment of treatment for men with prostate cancer appears on the horizon. This review paper presents the data on the most advanced diagnostic biomarkers of prostate cancer.

Download Full-text

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Novel Diagnostic Biomarkers of Prostate Cancer: An Update

Current Medicinal Chemistry ◽

10.2174/0929867325666180914115416 ◽

2019 ◽

Vol 26 (6) ◽

pp. 1045-1058 ◽

Cited By ~ 8

Author(s):

Umberto Anceschi ◽

Gabriele Tuderti ◽

Franco Lugnani ◽

Pier Mario Biava ◽

Gianni Malossini ◽

...

Keyword(s):

Prostate Cancer ◽

English Language ◽

Treatment Effectiveness ◽

Current Knowledge ◽

Specific Antigen ◽

Diagnostic Biomarkers ◽

Molecular Features ◽

Prostate Health Index ◽

Meta Analyses ◽

Prostate Health

Objective:In recent years, several biomarkers alternative to standard prostate specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available. The aim of this systematic review is to assess the current knowledge about alternative serum and urinary biomarkers for the diagnosis of PCa.Material and Methods:A research was conducted in Medline, restricted to English language articles published between December 2014 and June 2018 with the aim to update previously published series on PCa biomarkers. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria were used for selecting studies with the lowest risk of bias.Results:Emerging role and actual controversies on serum and urine alternative biomarkers to standard PSA for PCa diagnosis, staging and prognosis assessment, such as prostate health index (PHI), PCA3, ConfirmMDx, Aberrant PSA glycosylation, MiPS, miRNAs are critically presented in the current review.Conclusion:Although the use of several biomarkers has been recommended or questioned by different international guidelines, larger prospective randomized studies are still necessary to validate their efficacy in PCa detection, discrimination, prognosis and treatment effectiveness. To date, only PHI and 4Kscore have shown clinical relevance for discriminating more aggressive PCa. Furthermore, a new grading classification based on molecular features relevant for PCa risk-stratification and tailoring treatment is still needed.

Download Full-text

The performance of [-2]proPSA and prostate health index tumor markers in prostate cancer diagnosis

LaboratoriumsMedizin ◽

10.1515/labmed-2016-0056 ◽

2016 ◽

Vol 40 (6) ◽

Author(s):

Joško Osredkar ◽

Kristina Kumer ◽

Teja Fabjan ◽

Gregor Hlebič ◽

Blaže Podnar ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Markers ◽

Specific Antigen ◽

Area Under The Curve ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Prostatic Diseases ◽

Total Psa ◽

Prostate Health

AbstractBackground:Prostate-specific antigen (PSA) is an established tumor marker for the diagnosis of patients with prostate cancer. The aim of the study was to evaluate the performance of [-2]proenzyme PSA ([-2]proPSA) and prostate health index (PHI) tumor markers in the differential diagnosis between benign prostatic diseases and prostate cancer.Methods:Total PSA (tPSA), free PSA (fPSA) and [-2]proPSA were measured usingResults:For the prediction of a malignant histopathological result, the specificity at the 90% sensitivity level was 24.3% for [-2]proPSA, 32.4% for %[-2]proPSA, 28.4% for PHI, 18.9% for tPSA and 28.4% for the free-to-total PSA ratio. The area under the curve for [-2]proPSA, %[-2]proPSA, PHI, tPSA and the free-to-total PSA ratio was 0.663, 0.749, 0.742, 0.616 and 0.625, respectively.Conclusions:Our study found a moderate improvement over tPSA and %fPSA in detecting prostate cancer using the [-2]proPSA assay in patients with a tPSA range of 1.6–8.0 µg/L.

Download Full-text

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

Clinical Chemistry ◽

10.1373/clinchem.2012.195560 ◽

2013 ◽

Vol 59 (1) ◽

pp. 280-288 ◽

Cited By ~ 67

Author(s):

Carsten Stephan ◽

Klaus Jung ◽

Axel Semjonow ◽

Kai Schulze-Forster ◽

Henning Cammann ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Gene Fusion ◽

Specific Antigen ◽

Health Index ◽

Cancer Antigen ◽

Free Psa ◽

Prostate Health Index ◽

Prostate Cancer Antigen ◽

Prostate Health

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.

Download Full-text

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.

Download Full-text

Usefulness of the Prostate Health Index in Predicting the Presence and Aggressiveness of Prostate Cancer Among Korean Men

10.21203/rs.3.rs-424241/v1 ◽

2021 ◽

Author(s):

Jae-Yoon Kim ◽

Ji-Hyeong Yu ◽

Luck-Hee Sung ◽

Dae-Yeon Cho ◽

Hyun-Jung Kim ◽

...

Keyword(s):

Prostate Cancer ◽

Predictive Accuracy ◽

Specific Antigen ◽

Significant Proportion ◽

Multivariate Logistic Regression Analysis ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Total Psa ◽

Prostate Health

Abstract BackgroundWe aimed to evaluate the usefulness of the Beckman Coulter prostate health index (PHI) and compare it with total prostate specific antigen (PSA) and related derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in the Korean population.MethodsA 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.ResultsOf 140 patients, PCa was detected in 63 (45%), 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, 0.71, and 0.75, 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, 0.87, and 0.88, 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 = 0.031, p = 0.027) and significantly improved the predictive accuracy of a base multivariable model including age, tPSA, and %fPSA, using multivariate logistic regression analysis. (p = 0.015, p = 0.010). Additionally, at a cutoff PHI value >33.4, unnecessary biopsy could be avoided in 22.9% (32/140) cases, with no aggressive cancer patients missed.ConclusionThis 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.

Download Full-text

The validation results for APhiGT algorithm for clarification of prostate cancer staging before treatment (first step)

Cancer Urology ◽

10.17650/1726-9776-2019-15-2-42-52 ◽

2019 ◽

Vol 15 (2) ◽

pp. 42-52 ◽

Cited By ~ 1

Author(s):

N. S. Sergeeva ◽

T. E. Skachkova ◽

N. V. Marshutina ◽

K. M. Nushko ◽

I. M. Shevchuk ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Specific Antigen ◽

Area Under The Curve ◽

Cancer Staging ◽

Health Index ◽

Free Psa ◽

Prostate Health Index ◽

Total Psa ◽

Prostate Health

Background. We have previously described an algorithm APhiGT (Age, Prostate Health index, Gleason score, TNM stage) for staging of prostate cancer (PC) before treatment. The algorithm was developed by logistic regression on an educational selection (ES) of 337 PC cases. The algorithm includes data about the age of patients, the levels of total prostate-specific antigen (PSA), free PSA, [-2]proPSA and the ranked data of the Gleason score (by biopsy results) and T (by TNM).Objective. Validation of APhiGT on the validation selection (VS) of 83 PC cases was carried out in this work.Materials and methods. ROC analysis was performed in ES and VS.Results and сonclusion. It is established that area under the curve (AUC), characterizing the ability to divide clinically significant subgroups of patients (Gleason score <7 vs. Gleason score ≥7, рТ2 vs. рТ3, localized indolent PC vs. localized aggressive PC) for APhiGT both in ES and VS was significantly higher than AUC for total PSA, %[-2]proPSA in free PSA and prostate health index. At the same time, in all clinical subgroups of patients AUC for VS was lower than AUC for ES, which may be due to a significantly smaller size of VS compared to ES.

Download Full-text