Prostate Health Index Values Research Articles

Based on PI-RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4-20 ng/mL.

The study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) three lesions cohort. This study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor. Univariable and multivariable logistic regression analysis was conducted to ascertain hidden risk factors and constructed nomograms in PI-RADS three lesions cohort. In the whole cohort, the area under the ROC curve (AUC) of PHI is relatively high, which is 0.779. As radiographic parameters, the AUC of PI-RADS and ADC values was 0.702 and 0.756, respectively. The utilization of PHI and ADC values either individually or in combination significantly improved the diagnostic accuracy of the basic model. In PI-RADS three lesions cohort, the AUC for PCa was 0.817 in the training cohort and 0.904 in the validation cohort. The AUC for CSPCa was 0.856 in the training cohort and 0.871 in the validation cohort. When applying the nomogram for predicting PCa, 50.0% of biopsies could be saved, supplemented by 6.9% of CSPCa being missed. PHI and ADC values can be used as predictors of CSPCa. The nomogram included PHI, ADC values and other clinical predictors demonstrated an enhanced capability in detecting PCa and CSPCa within PI-RADS three lesions cohort.

Prostate Biopsy Strategy Integrating Prostate Health Index and Multiparametric Magnetic Resonance Imaging Optimizes the Predictive Value of Clinically Significant Prostate Cancer in Prostate Imaging Reporting and Data System Gray-Zone Imaging

Purpose: The Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI) are used as complementary tools for more accurate diagnosis in men with suspected prostate cancer (PCa). This study investigated whether the combination of PHI and mpMRI better predict clinically significant PCa (csPCa), defined as a Gleason score of ≥7. Materials and Methods: Ninety-four men with clinical suspicion of csPCa were prospectively included. PHI was determined before the prostate biopsy. A uroradiologist reviewed mpMRI findings by using the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS version 2.1). Fusion-targeted biopsy with systematic biopsy was performed in patients with any suspicious lesions on MRI (PI-RADS assessment category ≥3), whereas systematic biopsy was performed in patients without suspicious lesions. The diagnostic values of different biomarkers and PI-RADS were compared by the area under the receiver operating curve (area under the curve [AUC]) for detecting csPCa. Results: Forty-nine (52%) patients were diagnosed with csPCa. The csPCa group had higher median PHI and more abnormal MRI findings than did the non-csPCa group. The median total prostate-specific antigen (PSA) level was similar between the PI-RADS 3 and 4 lesion groups. The median PHI values increased and more patients were diagnosed as having csPCa with an increase in PI-RADS. The receiver operating characteristic curve indicated that PHI and MRI (AUC 0.85 and 0.82, respectively) predicted csPCa more accurately than did the total PSA, free PSA ratio, and PSA density. Adding PHI to mpMRI significantly increased the diagnostic accuracy for csPCa (P = 0.004). PHI remained the optimal biomarker in patients with “gray zone” PI-RADS 3 or PI-RADS 4 lesions. Conclusion: PHI can guide decision-making for prostate biopsy for patients with gray-zone mpMRI lesions. We proposed a biopsy strategy incorporating PHI and MRI which resulted in the avoidance of biopsies in 35% of the patients.

MP60-12 GENETIC POLYMORPHISMS AT 19q13.33 ARE ASSOCIATED WITH [-2]proPSA LEVELS AND PROVIDE ADDITIONAL PREDICTIVE VALUE TO PROSTATE HEALTH INDEX FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers (MP60)1 Sep 2021MP60-12 GENETIC POLYMORPHISMS AT 19q13.33 ARE ASSOCIATED WITH [-2]proPSA LEVELS AND PROVIDE ADDITIONAL PREDICTIVE VALUE TO PROSTATE HEALTH INDEX FOR PROSTATE CANCER Da Huang, Xiaohao Ruan, Danfeng Xu, and Rong Na Da HuangDa Huang More articles by this author , Xiaohao RuanXiaohao Ruan More articles by this author , Danfeng XuDanfeng Xu More articles by this author , and Rong NaRong Na More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002095.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate health index (PHI), a derivative of [-2]proPSA (p2PSA), has shown better accuracy than prostate-specific antigen (PSA) in prostate cancer (PCa) detection. However, the genetic predisposition of p2PSA remains unclear. This study is to investigate whether previously identified PSA-associated single nucleotide polymorphisms (SNPs) influence p2PSA or PHI levels and lead to potential clinical utility. METHODS: We conducted an observational prospective study with 2,268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ±100-kb window was tested for association with p2PSA and PHI levels using linear regression after adjusting for age and biopsy outcomes (PCa vs. non-PCa). Multivariable logistic regression (mLR) models were performed and internally validated using repeated 10-fold cross validation. We further calculated personalized PHI cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index. RESULTS: Among the 15,433 SNPs in 2,254 subjects after quality control, we detected 11 significant variants at 19q13.33 which were p2PSA-associated and independent of PCa. The most significant SNP, rs198978 in KLK2 (Pcombined=5.73×10-9), was also the only SNP significantly associated with PHI values after Bonferroni correction (Pcombined=3.20×10-6). Compared to the two commonly used PHI cutoffs of 27.0 and 36.0, the personalized PHI cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p<0.01). Decision curve analysis showed the mLR model (PHI + rs198978 genotype) could achieve a mildly higher net benefit than the original PHI for PCa risk thresholds between 20% and 35% (Figure). CONCLUSIONS: Rs198978, is independently associated with p2PSA values, and can improve diagnostic ability of PHI for PCa using personalized cutoff values. Source of Funding: None. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1046-e1046 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Da Huang More articles by this author Xiaohao Ruan More articles by this author Danfeng Xu More articles by this author Rong Na More articles by this author Expand All Advertisement Loading ...

Role of prostate health index to predict Gleason score upgrading and high-risk prostate cancer in radical prostatectomy specimens

We evaluated the role of prostate health index (PHI) in predicting Gleason score (GS) upgrading in International Society of Urological Pathology Grade Group (ISUP GG) 1 & 2 prostate cancer (PCa) or adverse pathologic outcomes at radical prostatectomy (RP). A total of 300 patients with prostate specific antigen ≥ 3 ng/mL, PHI and prostate biopsy (71 patients with RP included) were retrospectively included in the study. The primary study outcomes are PCa and clinically significant PCa (csPCa, defined as ISUP GG ≥ 2) diagnostic rate of PHI, and GS upgrading rate at RP specimen. The secondary outcomes are the comparison between GS upgrading and non-upgrading group, GS upgrading and high-risk PCa (ISUP GG ≥ 3 or ≥ pT3a) predictability of preoperative clinical factors. Overall, 139 (46.3%) and 92 (30.7%) were diagnosed with PCa and csPCa, respectively. GS upgrading rate was 34.3% in all patients with RP. Significant differences were shown in the total prostate volume (p = 0.047), the distribution of ISUP GG at biopsy (p = 0.001) and RP (p = 0.032), respectively. PHI values ≥ 55 [Odds ratio (OR): 3.64 (95% confidence interval (CI) = 1.05–12.68, p = 0.042] and presence of PI-RADS lesion ≥ 4 (OR: 7.03, 95% CI = 1.68–29.51, p = 0.018) were the significant predictors of GS upgrading in RP specimens (AUC = 0.737). PHI values ≥ 55 (OR: 9.05, 5% CI = 1.04–78.52, p = 0.046) is a significant factor for predicting adverse pathologic features in RP specimens (AUC = 0.781). PHI could predict GS upgrading in combination with PIRADS lesions ≥ 4 in ISUP GG 1 & 2. PHI alone could evaluate the possibility of high-risk PCa after surgery as well.

Use of the prostate health index in the detection of prostate cancer at all PSA levels (use of prostate health index in prostate cancer).

To determine the efficiency of prostate health index (PHI) calculated simultaneously during an ultrasound-guided fine-needle prostate biopsy in prostate cancer diagnosis. The present study included 258 subsequent patients who underwent a TRUS-guided biopsy in our clinic between August 2015 and March 2016 due to elevated blood levels of PSA and suspicion of prostate cancer. The total PSA, free PSA and pro-PSA were analysed in all patients before the procedure. The average age of 258 patients was 63.5 (36-91) years, and the mean PSA level and mean PHI values were 40.1 (0.12-2170) and 118 (0.41-1308), respectively. According to the PSA data, the patients were divided into two groups: the low PSA (<4ng/mL) group containing ten patients with adenocancer (31.2%) and 22 patients with BPH (68.8%) and the high PSA (>4ng/mL) group consisting of 86 patients with adenocancer (42.2%) and 118 (57.8%) with BPH. The sensitivity and specificity of PSA in detecting prostate adenocancer were calculated as 89.6% and 15.7%, respectively. Similarly, when a PHI level below 55 was accepted as low, and a PHI level at or above 55 was accepted as high, PHI's sensitivity and specificity were determined as 71.9% and 67.9%, respectively. The overall findings indicate that the specificity of PHI is higher than PSA in terms of prostate cancer detection.

Prostate Health Index and multiparametric magnetic resonance imaging to predict prostate cancer grade reclassification in active surveillance.

To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS). Between 2014 and 2019, we retrospectively identified 253 consecutive men in the Johns Hopkins AS programme who had mpMRI and PHI followed by a systematic ± targeted biopsy. PHI and PHI density (PHID) were evaluated across Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2) scores and compared to those with and without GR. Next, the negative predictive value (NPV) and area under the receiver operating curve (AUC) were calculated to compare the diagnostic value of PI-RADSv2 score combined with PHI, PHID, or prostate-specific antigen density (PSAD) for GR using their respective first quartile as a cut-off. Of the 253 men, 38 men (15%) had GR. Men with GR had higher PHI values (40.7 vs 32.0, P=0.001), PHID (0.83 vs 0.57, P=0.007), and PSAD (0.12 vs 0.10, P=0.037). A PI-RADSv2 ≤3 alone had a NPV of 91.6% for GR (AUC 0.67). Using a PHI cut-off of 25.6 in addition to PI-RADSv2 ≤3, the NPV and AUC were both increased to 98% and 0.70, respectively. Using a PSAD cut-off of 0.07ng/mL/mL with PI-RADSv2 had an AUC of 0.69 and NPV of 95.4%. PHI and PI-RADSv2 together could have avoided 20% of biopsies at the cost of missing 2.6% of GRs. The combination of PHI and mpMRI can aid in the prediction of GR in men on AS and may be useful for decreasing the burden of surveillance prostate biopsies.

PD48-07 CLINICAL USE OF PROSTATE HEALTH INDEX (PHI) FOR DETECTION OF PROSTATE CANCER IN 3,318 PATIENTS

You have accessJournal of UrologyProstate Cancer: Detection & Screening V (PD48)1 Apr 2020PD48-07 CLINICAL USE OF PROSTATE HEALTH INDEX (PHI) FOR DETECTION OF PROSTATE CANCER IN 3,318 PATIENTS John Richgels*, Joel Wackerbarth, Brian Helfand, and Alexander Glaser John Richgels*John Richgels* More articles by this author , Joel WackerbarthJoel Wackerbarth More articles by this author , Brian HelfandBrian Helfand More articles by this author , and Alexander GlaserAlexander Glaser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000942.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate health index (PHI) has consistently outperformed prostate-specific antigen (PSA) in detection of prostate cancer (PCa) and clinically-significant prostate cancer (csPCa) in the literature. We present the routine clinical use of PHI by multiple physicians in over 3,000 patients at a single tertiary care center. METHODS: Patients with a PHI result from 2017-2019 were identified using the Enterprise Data Warehouse. Clinical variables, PSA values, PHI scores, and prostate needle biopsy (PNB) results including Gleason Grade Group (GG) were extracted in accordance with an IRB-approved study. PHI scores were categorized into four risk categories (low PHI=0-26.9, average PHI=27-35.9, high 36-54.9, and very high PHI>55). The percentage of patients who underwent biopsy and subsequent prostate cancer GGs were compared with chi-square analysis and plotted with GraphPad Prism v8. ROC analysis was performed with R v3.5.1. RESULTS: Of the 3,318 unique patients who underwent PHI testing, 879 had a prior PNB and 2,440 were biopsy-naïve. Of the 879 patients with a prior PNB, 535 had a prior negative PNB, and 294 had a prior PNB with GG1 PCa. Increasing PHI values were associated with PNB and the likelihood of being diagnosed with PCa and csPCa in the total cohort and the subset of biopsy-naïve patients (p<0.0001, Figure 1A-B). Of 294 patients with a prior diagnosis of GG1 PCa who underwent repeat PNB after PHI testing, only 4% of patients with low-risk PHI were found to have csPCa, and the detection of GG1 PCa was expectedly similar across groups (p=0.11, Figure 1C). In 535 patients with a prior negative PNB, detection of csPCa was exclusively limited to patients with a high or very high PHI score (PHI>36; p<0.0001 Figure 1D). The area under the curve (AUC) to detect any PCa was 0.59 for PSA and 0.65 for PHI (p=0.02). The AUC to detect csPCa was 0.62 for PSA and 0.72 for PHI (p<0.001, Figure 2). CONCLUSIONS: We report the largest series to date of the use of PHI in routine clinical practice. PHI outperforms PSA in detection of PCa and csPCa. Men with a prior negative biopsy and PHI <36 may be at very low risk of csPCa. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e996-e997 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Richgels* More articles by this author Joel Wackerbarth More articles by this author Brian Helfand More articles by this author Alexander Glaser More articles by this author Expand All Advertisement PDF downloadLoading ...

Screening of BRCA2 mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( &gt; 4ng/ml and &gt; 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.

Clinical performance of prostate health index in men with tPSA>10 ng/ml: Results from a multicentric European study

BackgroundEvidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml. MethodsThe primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics. ResultsThe PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels. ConclusionsThe results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings.

MP02-01 CLINICAL UTILITY OF PHI (PROSTATE HEALTH INDEX) IN MEN WITH TPSA > 10 NG/ML. RESULTS FROM A MULTICENTRIC EUROPEAN STUDY

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2016MP02-01 CLINICAL UTILITY OF PHI (PROSTATE HEALTH INDEX) IN MEN WITH TPSA > 10 NG/ML. RESULTS FROM A MULTICENTRIC EUROPEAN STUDY Giovanni Lughezzani, Massimo Lazzeri, Rodolfo Hurle, NicolòMaria Buffi, Paolo Casale, Girolamo Fiorini, Roberto Peschechera, Luisa Pasini, Silvia Zandegiacomo, Vittorio Bini, Alessio Benetti, Alexander Haese, Joan Palou Redorta, Thomas McNicholas, Alexandre de la Taille, and Giorgio Guazzoni Giovanni LughezzaniGiovanni Lughezzani More articles by this author , Massimo LazzeriMassimo Lazzeri More articles by this author , Rodolfo HurleRodolfo Hurle More articles by this author , NicolòMaria BuffiNicolòMaria Buffi More articles by this author , Paolo CasalePaolo Casale More articles by this author , Girolamo FioriniGirolamo Fiorini More articles by this author , Roberto PeschecheraRoberto Peschechera More articles by this author , Luisa PasiniLuisa Pasini More articles by this author , Silvia ZandegiacomoSilvia Zandegiacomo More articles by this author , Vittorio BiniVittorio Bini More articles by this author , Alessio BenettiAlessio Benetti More articles by this author , Alexander HaeseAlexander Haese More articles by this author , Joan Palou RedortaJoan Palou Redorta More articles by this author , Thomas McNicholasThomas McNicholas More articles by this author , Alexandre de la TailleAlexandre de la Taille More articles by this author , and Giorgio GuazzoniGiorgio Guazzoni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1873AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The diagnostic accuracy of total PSA (tPSA) to determine the presence of prostate cancer (PCa) even in patients with high tPSA levels remains questionable. Evidences regarding the diagnostic accuracy of p2PSA and its derivatives (%p2PSA and Prostate Health Index - PHI) to predict the presence of PCa in individuals with high tPSA levels are lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10 ng/mL. METHODS The data analysis consisted of a nested case control study from the PRO-PSA Multicentric European Study (PROMEtheuS) project (detailed descriptions of study design, setting, ethics, centers and patients are available at http://www.controlled-trials.com/ISRCTN04707454). The study was designed to test the sensitivity, specificity, and accuracy of p2PSA and its derivatives, %p2PSA and the PHI in men with a tPSA > 10 ng/ml. in determining the presence of PCa at biopsy in comparison to tPSA, fPSA, and %fPSA. We calculated the number of prostate biopsies that could have been spared by using these markers to decide whether or not to perform a biopsy. A secondary end-point was to determine the relationship between the index tests (p2PSA, %p2PSA and PHI) and PCa characteristics. Multivariable logistic regression models were complemented by predictive accuracy analysis. RESULTS PCa was diagnosed in 136 out of 262 patients (51.9%). Specifically, 30 patients were diagnosed with a Gleason score (GS) 6 PCa (22.1%), while 66 (48.5%) and 40 (29.4%) were diagnosed with a GS 7 and 8-10 PCa, respectively (29.4%). Total PSA, p2PSA, %p2PSA and PHI values were significantly higher (p<0.005) and %fPSA values significantly lower (p<0.0001) in patients with PCa relative to those with a negative biopsy. In accuracy analyses, %p2PSA and PHI (AUCs: 0.80 and 0.81 respectively) were the most accurate predictors of PCa, and significantly outperformed tPSA (AUC: 0.61), fPSA (AUC: 0.54), %fPSA (AUC: 0.67) and p2PSA (AUC: 0.66) (all p≤0.001). In multivariable logistic regression models, both %p2PSA and PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by a 6.9% and 6.7% extent (p<0.05). The use %p2PSA and PHI in the biopsy decision path would decrease the number of unnecessary biopsies by a 48.4-50.0% extent, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to p2PSA, %p2PSA and PHI levels. CONCLUSIONS The results of our study support the diagnostic effectiveness of %p2PSA and PHI even in patients with a tPSA >10 ng/mL. Further validation studies with larger sample size are needed to corroborate our findings. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e9 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Giovanni Lughezzani More articles by this author Massimo Lazzeri More articles by this author Rodolfo Hurle More articles by this author NicolòMaria Buffi More articles by this author Paolo Casale More articles by this author Girolamo Fiorini More articles by this author Roberto Peschechera More articles by this author Luisa Pasini More articles by this author Silvia Zandegiacomo More articles by this author Vittorio Bini More articles by this author Alessio Benetti More articles by this author Alexander Haese More articles by this author Joan Palou Redorta More articles by this author Thomas McNicholas More articles by this author Alexandre de la Taille More articles by this author Giorgio Guazzoni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serum Vitamin D is Not Helpful for Predicting Prostate Cancer Aggressiveness Compared with the Prostate Health Index

We evaluated the usefulness of serum 25-hydroxyvitamin D as a marker of aggressive prostate cancer and for active surveillance compared to PHI (Prostate Health Index). Of 480 prospectively biopsied men 222 had prostate cancer and 258 had no evidence of malignancy. In all men prostate specific antigen was lessthan 20 ng/ml. We measured 25-hydroxyvitamin D, prostate specific antigen, free prostate specific antigen and -2proPSA using a commercially available immunoassay system. PHI was calculated according to the equation, -2proPSA/free prostate specific antigen × √PSA. We determined 25-hydroxyvitamin D using a 2-step competitive binding immunoenzymatic vitamin D assay. The 25-hydroxyvitamin D concentrations were not associated with Gleason grade according to the 2014 ISUP (International Society of Urological Pathology) consensus conference Gleason grading system. PHI values were higher with increasing Gleason grade. Median 25-hydroxyvitamin D did not differ between men with prostate cancer vs no evidence of malignancy (50.6 vs 48.2 nmol/l, p = 0.192) or in ISUP Gleason subgroups despite seasonal variations of 25-hydroxyvitamin D. However, PHI values significantly differed between the subgroup with no evidence of malignancy and all Gleason subgroups (p <0.0001). The ROCs of all men revealed an advantage of PHI over 25-hydroxyvitamin D (AUC 0.78 vs 0.535, p <0.0001). PHI could also significantly better separate patients with no evidence of malignancy from those with nonaggressive disease (ISUP Gleason grade 1) from those with aggressive prostate cancer (ISUP Gleason grades 2-5). It remains highly improbable that 25-hydroxyvitamin D could be used as decision or selection marker for aggressive prostate cancer or for active surveillance compared to accepted markers, as recently suggested.

PD46-02 MULTICENTER EVALUATION OF THE PROSTATE HEALTH INDEX (PHI) FOR DETECTION OF AGGRESSIVE PROSTATE CANCER IN BIOPSY-NAÏVE MEN

You have accessJournal of UrologyProstate Cancer: Detection and Screening V1 Apr 2015PD46-02 MULTICENTER EVALUATION OF THE PROSTATE HEALTH INDEX (PHI) FOR DETECTION OF AGGRESSIVE PROSTATE CANCER IN BIOPSY-NAÏVE MEN Claire de la Calle, Dattatraya Patil, John Wei, Douglas Scherr, Lori Sokoll, Daniel Chan, Javed Siddiqui, Juan Miguel Mosquera, Mark Rubin, and Martin Sanda Claire de la CalleClaire de la Calle More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , John WeiJohn Wei More articles by this author , Douglas ScherrDouglas Scherr More articles by this author , Lori SokollLori Sokoll More articles by this author , Daniel ChanDaniel Chan More articles by this author , Javed SiddiquiJaved Siddiqui More articles by this author , Juan Miguel MosqueraJuan Miguel Mosquera More articles by this author , Mark RubinMark Rubin More articles by this author , and Martin SandaMartin Sanda More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2733AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Prostate Health Index (PHI) is a new formula that combines three well-known biomarkers: total PSA, free PSA and [-2]proPSA (p2PSA). PHI has been shown to increase specificity of the individual biomarkers in cohorts comprised of subjects with previous prostate biopsies as well as subjects with no history of biopsy. Here we tested PHI's ability to discern aggressive prostate cancer from indolent or no cancer on a biopsy-naïve population. METHODS Two independent prospective cohorts of 561 and 395 subjects were used for validation of the results. Each cohort recruited patients at different institutions. Criteria of inclusion were no history of prostate cancer or of prostate biopsy. Each subject had serum collected for total pre-biopsy PSA, %free PSA and p2PSA testing on the Beckman Coulter Access 2 prior to biopsy. PHI was calculated as (p2PSA/freePSA)∗sqrt (PSA). Bootstrap sampling provided the estimates for the performance measures including sensitivity and specificity. PHI cut point and corresponding specificities were calculated at fixed sensitivities of 95%, 90%, and 80%. Improvement in specificity was determined by bootstrap estimated standard error. RESULTS In the primary cohort, 20.3% of patients were found to have aggressive prostate cancer (Gleason score > 7). Higher PHI values were significantly associated with Gleason 7 score or higher. Mean PHI was 74.6 (SD ± 68.2) in the Gleason 7 score or higher group versus 32.2 (SD ± 18.9) in the less than Gleason 7 group (p<0.001). PHI's ability to detect aggressive prostate cancer yielded an AUC of 0.815 and its specificity was significantly higher than total pre-biopsy PSA and % free PSA specificities. At 95% sensitivity PHI specificity was 36.0% versus 17.2% and 19.4% for total pre-biopsy PSA and % free PSA respectively. At 95% sensitivity in detecting aggressive prostate cancer, the optimal PHI cut point was 24, which would help avoid 41% of unnecessary biopsies. Validation cohort analysis confirmed the improvement of specificity with PHI overall. The pre-determined PHI cutoff of 24 led to 36% biopsies avoided and very few aggressive cancers missed. CONCLUSIONS These results demonstrate that the prostate health index detects aggressive prostate cancer with a better specificity than total PSA and percent free PSA in a biopsy-naïve population, and could be a useful tool to decrease unnecessary prostate biopsies. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e956-e957 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claire de la Calle More articles by this author Dattatraya Patil More articles by this author John Wei More articles by this author Douglas Scherr More articles by this author Lori Sokoll More articles by this author Daniel Chan More articles by this author Javed Siddiqui More articles by this author Juan Miguel Mosquera More articles by this author Mark Rubin More articles by this author Martin Sanda More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical performance of serum isoform [‐2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged &lt;60 years: results from a multicentric European study

To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years. The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses. Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05). PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.

Clinical use of [-2]proPSA (p2PSA) and its derivatives (%p2PSA and Prostate Health Index) for the detection of prostate cancer: a review of the literature.

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Relationship of Chronic Histologic Prostatic Inflammation in Biopsy Specimens With Serum Isoform [-2]proPSA (p2PSA), %p2PSA, and Prostate Health Index in Men With a Total Prostate-specific Antigen of 4-10 ng/mL and Normal Digital Rectal Examination

To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making toavoid unnecessary biopsies in patients with CHPI and elevated tPSA value.

Clinical performance of serum prostate‐specific antigen isoform [‐2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project

To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively). %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness.

1926 SERUM ISOFORM [-2]PROPSA (P2PSA) AND ITS DERIVATIVES, NAMELY %P2PSA AND PHI (PROSTATE HEALTH INDEX) IN MEN YOUNGER THAN 60 YEARS OF AGE FOR PREDICTION OF PROSTATE CANCER. RESULTS FROM A MULTICENTRIC EUROPEAN STUDY (PROMETHEUS PROJECT)

1926 SERUM ISOFORM [-2]PROPSA (P2PSA) AND ITS DERIVATIVES, NAMELY %P2PSA AND PHI (PROSTATE HEALTH INDEX) IN MEN YOUNGER THAN 60 YEARS OF AGE FOR PREDICTION OF PROSTATE CANCER. RESULTS FROM A MULTICENTRIC EUROPEAN STUDY (PROMETHEUS PROJECT)

A pilot study evaluating serum pro-prostate-specific antigen in patients with rising PSA following radical prostatectomy

[-2]pro-prostate-specific antigen (2pPSA), a proform of PSA, is a new marker in patients at risk of prostate cancer. We explored the potential role of 2pPSA in the identification of patients with metastatic progression following radical prostatectomy for prostate cancer. Seventy-six patients with biochemical (PSA) recurrence following radical prostatectomy were studied retrospectively. Diagnostic imaging performed at the time of biochemical recurrence confirmed metastatic disease in 31 of the 76 patients. Serum samples were collected and stored at the time of imaging-confirmed metastatic progression or at the most recent procedure for patients with negative imaging. Median values of PSA, free PSA (fPSA), %fPSA, 2pPSA and prostate health index (PHI) were compared between metastatic and non-metastatic patients by the Mann-Whitney U test. The results of each test were then correlated with metastatic status by univariate and multivariate logistic regression analysis. PSA, fPSA, %fPSA, 2pPSA serum concentrations and PHI values were statistically significantly higher in patients with metastatic disease. Results of the multivariate analysis revealed that 2pPSA remained a statistically significant predictor of imaging-proven metastatic prostate cancer among patients with biochemical recurrence. At a cut-off value of 12.25 pg/ml, 2pPSA outperformed the other markers in terms of sensitivity and specificity (97 and 80%, respectively) with respect to imaging-confirmed metastatic progression. This is the first study suggesting that 2pPSA predicts diagnostic imaging-proven metastatic disease in previously resected prostate cancer patients with biochemical recurrence. Our results merit validation in a prospective study.