Prostate Health Index Research Articles

The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.

EDITORIAL COMMENT

The authors report on the largest clinical evaluation of Prostate Health Index (PHI) assay in African American (AA) men for the prediction of Gleason grade group (GG) 2-5 prostate cancer (PCa). 1 Morris K Kotamarti S Polascik T Moul J. Re-thinking how we use prostate health index for African American Men. Urology. 2023; (S0090-4295(23)00176-0) Abstract Full Text Full Text PDF Scopus (0) Google Scholar They report that the required threshold to achieve a sensitivity >90% coincides with a poor specificity; this only permits 4.7% of Black men to avoid a biopsy even though over half of biopsies were negative or GG 1 PCa. Their findings call in to question whether the assay is accurate enough to be relied upon for Black men. There is, however, a potential for bias from its retrospective and heterogeneous nature. The fact that 18.2% of men did not proceed to biopsy, 36.4% had prostate Magnetic Resonance Imaging (MRI), 13.4% had a fusion biopsy and men were seen in a tertiary care setting could enrich the population for any PCa and GG 2-5 PCa and overestimate risk for each stratum, including the 0-26.9 strata where the authors detected any PCa (48.0%) in 13 of 22 fusion biopsy patients. A biopsy-naïve/MRI-naïve cohort would be a better comparator, since the risk strata that PHI uses is based on a cohort that predates the use of MRI Prostate Imaging–Reporting and Data System (PIRADS) scores. 2 Catalona WJ Partin AW Sanda MG et al. A multi-center study of [− 2] pro41 prostate-specific antigen (PSA) in combination with PSA and free PSA for prostate cancer detection in the 2.0 to 10.0 ng/mL PSA range. J Urol. 2011; 185: 1650 Crossref PubMed Scopus (375) Google Scholar ,3 Barentsz JO Richenberg J Clements R et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012; 22: 746-757 Crossref PubMed Scopus (1906) Google Scholar Nevertheless, it shows that the value of PHI in a ‘real-world’ setting may be limited. Their findings also dovetail with the study on Black men with elevated prostate-specific antigen (PSA) by Babajide et al where the probability of overall and GG 2-5 PCa were higher at each of the established PHI risk strata. 4 Babajide R Carbunaru S Nettey OS et al. Performance of prostate health index in biopsy naïve black men. J Urol. 2021; 205: 718-724 Crossref PubMed Scopus (9) Google Scholar Data in other racial groups also suggests that optimal thresholds of PHI vary across populations. 5 Tan LG Tan YK Tai BC et al. Prospective validation of %p2PSA and the prostate health index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1. Asian J Androl. 2017; 19: 286-290 Crossref PubMed Scopus (27) Google Scholar , 6 Ferro M Bruzzese D Perdona S et al. Prostate Health Index (PHI) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2–10 ng/ml. PLoS One. 2013; 8: e67687 Crossref PubMed Scopus (87) Google Scholar , 7 Loeb S Sanda MG Broyles DL et al. The prostate health index selectively identifies clinically significant prostate cancer. J Urol. 2015; 193: 1163-1169 Crossref PubMed Scopus (197) Google Scholar

Risk Stratification of Low-risk Prostate Cancer: Individualizing Care in the Era of Active Surveillance.

While active surveillance is the preferred management for most men with low-risk prostate cancer, a subset may harbor more aggressive disease. In this review we examine the evidence underlying an accurate and nuanced assessment of oncologic risk in these men. We performed a nonsystematic literature review current to January 2023 on PubMed for articles relating to clinical, pathological, molecular, and imaging-based modalities available for risk assessment in men with low-risk prostate cancer. Relevant articles were reviewed by the authors and evidence was summarized. Many tools are available to personalize clinical decision-making for men with low-risk prostate cancer. Total volume of cancer, PSA density, and presence of ductal components have been consistently and strongly associated with current or future evidence of higher-grade disease. PSA kinetics, Prostate Imaging Reporting & Data System 4/5 lesions on MRI, perineural invasion, germline mutations, and genomic classifiers all appear to be associated with an increased risk, although are not as extensively validated. Race, percent free PSA, and other serum biomarkers such as Prostate Health Index and 4Kscore do not appear to be associated with long-term elevated risk. Long-term prognosis for men diagnosed with low-risk prostate cancer is excellent. There are many factors which should be routinely integrated into the initial management decision as well as determining intensity and frequency of active surveillance. Development of comprehensive multivariable instruments to guide clinical decisions is encouraged.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

MP44-01 OPTIMAL SEQUENCING OF MRI AND PROSTATE HEALTH INDEX AS RISK STRATIFICATION TOOLS IN A BIOMARKER-IMAGING PROSTATE CANCER SCREENING PATHWAY

You have accessJournal of UrologyCME1 Apr 2023MP44-01 OPTIMAL SEQUENCING OF MRI AND PROSTATE HEALTH INDEX AS RISK STRATIFICATION TOOLS IN A BIOMARKER-IMAGING PROSTATE CANCER SCREENING PATHWAY Yi Quan Tan, Woon Chau Tsang, Ziting Wang, and Edmund Chiong Yi Quan TanYi Quan Tan More articles by this author , Woon Chau TsangWoon Chau Tsang More articles by this author , Ziting WangZiting Wang More articles by this author , and Edmund ChiongEdmund Chiong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To determine the optimal sequence of MRI and Prostate Health Index (PHI) as risk stratification tools in the early detection of prostate cancer. METHODS: 181 men presented between Aug 2016 and Oct 2020, undergoing MRI and PHI before MRI-fusion biopsy. Biopsy included targeted and saturation cores. PIRADS score, PHI, and histology results were recorded. To determine the optimal sequence of MRI and PHI, modelling was performed with 4 pathways designed to guide biopsy decisions. PIRADS 3 or more, and PHI of 30 or more, were considered as screen-positive tests and patients proceeded with biopsy. The 4 pathways were: (1) PHI first then MRI to stratify PHI-negative cases; (2) MRI first then PHI to stratify MRI-negative cases; (3) PHI first then MRI to stratify PHI-positive cases; and (4) MRI first then PHI to stratify MRI-positive cases. For each pathway, the key outcomes measured were (1) the percentage of biopsies avoided, (2) clinically-significant cancers missed (Grade Group 2 and above); and (3) unnecessary biopsies (negative and Grade Group 1). RESULTS: Overall cancer detection rate was 61.3%, and the clinically-significant cancer detection rate was 37.6%. 88.4% had a PIRADS 3 or higher lesion, and 82.9% had a PHI level of 30 or more. In Pathway 1, where PHI was used first-line, with MRI as second-line when PHI was negative, 2.21% of biopsies would be avoided, and no clinically-significant cancers would be missed. In Pathway 2, where MRI was used first-line, with PHI as second-line when MRI was negative, 2.21% of biopsies would be avoided, and no clinically significant cancers would be missed. In Pathways 3 and 4, 26% of biopsies were avoided, yet 3.9% of clinically-significant cancers would be missed (see Figure 1). CONCLUSIONS: The combination of PHI and MRI did not miss any clinically-significant cancers. This was only evident in the pathways where the second-line test was used in cases when the first-line test was negative. Whether PHI or MRI was sequenced as the first-line test did not affect the overall diagnostic performance in the detection of prostate cancer. We propose that MRI and PHI be combined to achieve the optimal screening performance for prostate cancer detection. Source of Funding: There are no sources of funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e610 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Quan Tan More articles by this author Woon Chau Tsang More articles by this author Ziting Wang More articles by this author Edmund Chiong More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

MP38-04 BASELINE PROSTATE HEALTH INDEX RISK CATEGORY AND RISK CATEGORY CHANGES DURING ACTIVE SURVEILLANCE PREDICT GRADE RECLASSIFICATION

You have accessJournal of UrologyCME1 Apr 2023MP38-04 BASELINE PROSTATE HEALTH INDEX RISK CATEGORY AND RISK CATEGORY CHANGES DURING ACTIVE SURVEILLANCE PREDICT GRADE RECLASSIFICATION Claire De La Calle, Yuezhou Jing, Mufaddal Mamawala, Patricia Landis, Katarzyna Macura, Bruce Trock, Jonathan Epstein, Lori Sokoll, and Christian Pavlovich Claire De La CalleClaire De La Calle More articles by this author , Yuezhou JingYuezhou Jing More articles by this author , Mufaddal MamawalaMufaddal Mamawala More articles by this author , Patricia LandisPatricia Landis More articles by this author , Katarzyna MacuraKatarzyna Macura More articles by this author , Bruce TrockBruce Trock More articles by this author , Jonathan EpsteinJonathan Epstein More articles by this author , Lori SokollLori Sokoll More articles by this author , and Christian PavlovichChristian Pavlovich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We sought to determine if repeated prostate health index (PHI) tests during active surveillance (AS) are of clinical value in a contemporary AS cohort followed with multiparametric magnetic resonance imaging (mpMRI) and biopsies of the prostate. METHODS: We identified 382 patients in our AS program with at least one mpMRI and one PHI test, of which 241 had at least two PHI tests. All men had ≥Grade group 1 (GG1) prostate cancer on diagnostic and confirmatory biopsy. Grade reclassification (GR) was defined as ≥GG2 identified on surveillance biopsy. PHI risk categories 1-4 were as defined by the manufacturer. A multivariable Cox proportional hazard regression model was performed to evaluate the association between baseline PHI risk category and GR, and change in PHI risk categories over time and GR, respectively. RESULTS: Men with baseline PHI scores in the highest risk categories had lower rates of GR-free survival (log-rank p<0.001; Figure). On multivariable Cox regression baseline PHI risk category was a predictor of GR (model C-index 0.769; Table A). Men with an increase in PHI risk category or consistently high PHI (risk category 3-4) (compared to baseline PHI) experienced more upgrading (36/112=32.1% vs 27/129=20.9%, p=0.048). On multivariable Cox proportional hazards model with PHI risk category as a time-dependent variable, increasing PHI risk category demonstrated increasing association with GR (model C-index 0.762, Table B). CONCLUSIONS: Both baseline PHI risk category and PHI risk category over time were predictors of GR after confirmatory biopsy. The model with PHI category changes over time did not perform better than the model with baseline PHI risk category. PHI is a non-invasive and easy to obtain test, so further evaluation of its clinical utility in reducing the frequency of mpMRI and/or surveillance biopsies and in improving risk stratification is warranted. Source of Funding: Ralph T. and Esther L. Warburton Foundation and Dr. Hugh Judge Jewett Fellowship in Urologic Oncology © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e524 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claire De La Calle More articles by this author Yuezhou Jing More articles by this author Mufaddal Mamawala More articles by this author Patricia Landis More articles by this author Katarzyna Macura More articles by this author Bruce Trock More articles by this author Jonathan Epstein More articles by this author Lori Sokoll More articles by this author Christian Pavlovich More articles by this author Expand All Advertisement PDF downloadLoading ...

MP40-20 CAN WE PREDICT FOR MISSED CLINICALLY SIGNIFICANT PROSTATE CANCERS ON MRI-TARGETED BIOPSY ALONE?

You have accessJournal of UrologyCME1 Apr 2023MP40-20 CAN WE PREDICT FOR MISSED CLINICALLY SIGNIFICANT PROSTATE CANCERS ON MRI-TARGETED BIOPSY ALONE? Woon Chau Tsang, Kaiying Wang, Abner Quek, Ziting Wang, Edmund Chiong, and Qinghui Wu Woon Chau TsangWoon Chau Tsang More articles by this author , Kaiying WangKaiying Wang More articles by this author , Abner QuekAbner Quek More articles by this author , Ziting WangZiting Wang More articles by this author , Edmund ChiongEdmund Chiong More articles by this author , and Qinghui WuQinghui Wu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MRI-Targeted prostate biopsy (TBx) strategy has been shown to diagnose more clinically significant prostate cancer (csPCa) and less clinically insignificant prostate cancer (ciPCa). Currently, the yield of systematic or saturation biopsy in addition to TBx remains remain unclear. This study aims to evaluate for factors that may predict for csPCa that are missed on TBx alone. METHODS: From 2015 to 2022, we collected prospective single-centre data of consecutive patients who underwent prostate biopsy. We included patients who were biopsy-naïve, had prior negative biopsies, or were on active surveillance for low risk prostate cancer. mpMRI-ultrasound fusion-guided robotic-assisted TBx was performed for every lesion of Prostate Imaging Reporting and Data System (PIRADS) 3 and above, and every patient additionally received saturation biopsy (SBx). Patient data, MRI lesion characteristics, PIRADS score and biopsy results were evaluated. csPCa was defined as ISUP grade group 2 and above. RESULTS: 499 men underwent combined TBx and SBx. The median serum PSA was 7.31ug/L. The overall cancer detection rate was 65.7%, where csPCa rate was 45.1%. The overall cancer and csPCa rates for TBx only vs TBx plus SBx, was 52.9% vs 65.7% (p<0.01), and 39.9% vs 45.1% (p=0.10) respectively. If only TBx was performed, 19.5% of all cancers and 11.5% of csPCa would have been missed. Patients with missed csPCa on TBx only had lower PSA (7.75 vs 10.6, p<0.01), higher prostate volume (59.5 vs 42.9cc, p=0.04), and lower PSA density (0.164 vs 0.271, p<0.01). They also had lower prostate health index (PHI) score (50.6 vs 61.9, p=0.04), although PHI density was similar (1.22 vs 1.56, p=0.09). A smaller index lesion diameter was also predictive of missed csPCa on TBx (8.70 vs 12.2 mm, p<0.01). Patients with PIRADS 3 index lesions were more likely to have missed csPCa on TBx than PIRADS 4 and 5, with a missed csPCa rate of 25.8% vs 11.8% vs 3.45% (p<0.01) respectively. Age, number of lesions on mpMRI, and indication for biopsy were not predictive of missed csPCa. CONCLUSIONS: In our series, TBx alone strategy can miss 11.5% of csPCa. Factors predictive of missed csPCa include initial low PSA level, larger prostate volume, low PSA density, low PHI, small index lesion diameter and lower PIRADS score of the index lesion. A nomogram is created to aid decision making on patient selection to omit systematic biopsy when performing TBx. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e553 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Woon Chau Tsang More articles by this author Kaiying Wang More articles by this author Abner Quek More articles by this author Ziting Wang More articles by this author Edmund Chiong More articles by this author Qinghui Wu More articles by this author Expand All Advertisement PDF downloadLoading ...

MP44-11 DETECTION OF SUBSEQUENT CLINICALLY SIGNIFICANT PROSTATE CANCER FOLLOWING INITIAL DECISION TO FORGO BIOPSY IN THE MULTIPARAMETRIC MRI ERA

You have accessJournal of UrologyCME1 Apr 2023MP44-11 DETECTION OF SUBSEQUENT CLINICALLY SIGNIFICANT PROSTATE CANCER FOLLOWING INITIAL DECISION TO FORGO BIOPSY IN THE MULTIPARAMETRIC MRI ERA Eric Li, Anna Busza, Mohammad Siddiqui, Jonathan Aguiar, Parth Shah, Ashorne Mahenthiran, Jasmine Lin, Moataz Soliman, Sai Kumar, Mary Kate Keeter, Clayton Neill, Xinlei Mi, Quan Mai, Edward Schaeffer, Hiten Patel, and Ashley Ross Eric LiEric Li More articles by this author , Anna BuszaAnna Busza More articles by this author , Mohammad SiddiquiMohammad Siddiqui More articles by this author , Jonathan AguiarJonathan Aguiar More articles by this author , Parth ShahParth Shah More articles by this author , Ashorne MahenthiranAshorne Mahenthiran More articles by this author , Jasmine LinJasmine Lin More articles by this author , Moataz SolimanMoataz Soliman More articles by this author , Sai KumarSai Kumar More articles by this author , Mary Kate KeeterMary Kate Keeter More articles by this author , Clayton NeillClayton Neill More articles by this author , Xinlei MiXinlei Mi More articles by this author , Quan MaiQuan Mai More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Hiten PatelHiten Patel More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Advanced biomarker tests and multiparametric prostate MRI (mpMRI) have improved risk stratification for detection of clinically significant prostate cancer (csPCa, ISUP Grade Group 2+). However, subsequent testing and detection of csPCa among men forgoing initial biopsy has not been well described. Here we characterize the subsequent detection of csPCa in patients who had an initial MRI without biopsy. METHODS: We retrospectively identified biopsy-naïve men presenting with elevated PSA 2-20 ng/mL from March 2018 to June 2021 who received evaluation with mpMRI before biopsy consideration. Initial and follow-up clinicopathologic data including PSA, Prostate Health Index (PHI), mpMRI, and pathology reports were obtained. T-test, Chi-squared, Wilcoxon rank sum test, and multivariable logistic regression were performed. RESULTS: 1494 men underwent mpMRI for initial evaluation, after which 463 (31%) did not pursue biopsy. On multivariable analysis, PSA density (PSAD) <0.1, PHI <55, and PIRADS 1-2 on mpMRI were significant predictors of omitting initial prostate biopsy. Of the men who did not initially receive biopsy, 353 men had minimum 6 months follow-up with median follow-up of 1.8 years. 15% (53/353) underwent repeat mpMRI. Overall, 2% of men (n=7) who originally omitted biopsy with follow-up were subsequently diagnosed with csPCa, six on subsequent prostate biopsy and one with incidental csPCa after holmium enucleation of the prostate (HoLEP). All patients diagnosed with csPCa had PIRADS 4 or 5 on repeat MRI. CONCLUSIONS: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI is low at 2%. Of the patients followed by serum biomarkers (i.e. PSA) with for cause MRIs, only the patients who developed PIRADS 4 or 5 lesions were found to have csPCa. Our institutional experience suggests that decisions to omit biopsy after MRI are often safe; additionally, if there is clinical suspicion leading to a repeat MRI, biopsy can again be omitted for mpMRIs scored as PIRADS 1-3. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e615 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Li More articles by this author Anna Busza More articles by this author Mohammad Siddiqui More articles by this author Jonathan Aguiar More articles by this author Parth Shah More articles by this author Ashorne Mahenthiran More articles by this author Jasmine Lin More articles by this author Moataz Soliman More articles by this author Sai Kumar More articles by this author Mary Kate Keeter More articles by this author Clayton Neill More articles by this author Xinlei Mi More articles by this author Quan Mai More articles by this author Edward Schaeffer More articles by this author Hiten Patel More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...

Optimizing detection of clinically significant prostate cancer through nomograms incorporating mri, clinical features, and advanced serum biomarkers in biopsy naïve men.

To develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features. Nomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2-20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022. 1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa. Here we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2-20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions.

Do PHI and PHI density improve detection of clinically significant prostate cancer only in the PSA gray zone?

Prostate health index (PHI) is a predictive biomarker of positive prostate biopsy. The majority of evidence refers to its use in the PSA gray zone (4-10ng/mL) and negative digital rectal exam (DRE). We aim to evaluate and compare the predictive accuracy of PHI and PHI density (PHId) with PSA, percentage of free PSA and PSA density, in a wider range of patients for the detection of clinically significant prostate cancer (csPCa). Multicenter prospective study that included patients suspicious of harboring prostate cancer. Non-probabilistic convenience sampling, where men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate and compare diagnostic accuracy AUC and decision curve analysis (DCA) were calculated. All these procedures were performed for the overall sample and the following subsamples: PSA<4ng/ml; PSA 4-10ng/ml; PSA 4-10ng/ml plus negative DRE and PSA>10ng/ml. Among the 559 men included, 194 (34.7%) were diagnosed of csPCa. PHI and PHId outperfomed PSA in all subgroups. PHI best diagnostic performance was found in PSA 4-10ng/ml with negative DRE (sensitivity 93.33, NPV 96.04). Regarding AUC, significant differences were found between PHId and PSA in the subgroup of PSA 4-10ng/ml, whatever DRE status. In DCA, PHI density shows the highest net benefit. PHI and PHId outperfom PSA in csPCa detection, not only in the PSA grey zone with negative DRE, but also in a wider range of PSA values. There is an urgent need of prospective studies to established a validated threshold and its incorporation in risk calculators.

Comparisons of the diagnostic accuracy across prostate health index, prostate health index density, and percentage free prostate-specific antigen for clinically significant prostate cancer: a prospective diagnostic study.

As the novel serum biomarkers, it has not been clearly clarified that the diagnostic accuracy of prostate health index (PHI) and prostate health index density (PHID) are superior to that of percentage free prostate-specific antigen (%fPSA) in detection of clinically significant prostate cancer (csPCa), especially in the gray zone. Therefore, this study aimed to compare the diagnostic value of PHI, PHID, and %fPSA for csPCa in the patients with prostate-specific antigen (PSA) >4 ng/mL and those with PSA within 4-10 ng/mL. In this study, the serum samples and clinicopathological features were prospectively obtained from the patients who underwent prostate biopsy between September 2019 and December 2020. According to the inclusion criteria, the patients with total PSA (tPSA) >4 ng/mL, prostate magnetic resonance imaging or ultrasound clearly suggesting an occupying lesion were enrolled in this study. The patients with Gleason score ≥7 indicated csPCa. The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. Among the 296 patients (mean age 67.5 years, median tPSA 7.94 ng/mL) included in this study, there were 54 in the csPCa group (mean age 70.4 years, median tPSA 11.0 ng/mL) and 242 in the non-csPCa group (mean age 66.8 years, median tPSA 7.67 ng/mL). Based on the PSA level, there were 198 patients with PSA within the gray zone, which included 40 patients in the csPCa group and 158 in the non-csPCa group. In all patients, the sensitivity of PHID for detecting csPCa was 96.30%, and the specificity was 33.06% with the cut-off value of 0.51. Moreover, both PHID and PHI did better in the diagnosis of csPCa (AUC: 0.880 and 0.867, respectively) compared with other PSA derivative markers. Similarly, in the patients with PSA level in the gray zone, the diagnostic accuracy of PHID and PHI in predicting csPCa (AUC: 0.788 and 0.777, respectively) were better than other PSA derivative markers. PHID presented the better diagnostic accuracy in predicting csPCa in patients with PSA in the gray zone than other PSA derivative markers, which could be a promising biomarker for making the biopsy strategy.

A prospective evaluation of the effect of finasteride on prostate health index (phi).

5-alpha reductase inhibitor (5ARI) reduces prostate-specific antigen (PSA) by half but its effect on prostate health index (phi) is unknown. This study aims to investigate this effect and to enable accurate interpretation of phi in men with elevated PSA and on 5ARI. This is a prospective study evaluating the effect of finasteride on PSA, free PSA (fPSA), [ - 2]proPSA (p2PSA) and phi at 6 and 12 moths in men with PSA 4-20ng/mL, no prior 5ARI use, and one negative prostate biopsy within 6months before recruitment. The 5ARI Finasteride (5mg/day) for 1year was offered if International Prostatic Symptom Score (IPSS) was ≥ 8 at baseline. 5ARI group included patients taking finasteride, while control group included patients not on finasteride. The blood results were compared with t-test between baseline and different time points in each group and between groups at 1year. 164 men fit the inclusion criteria and 150 were analyzed. In 5ARI group (n = 100) at 1year, mean PSA reduced by 51.4% from 8.9(± SD 3.7) to 4.4(± SD 2.8)ng/mL (paired t-test, p < 0.001), fPSA reduced by 52.4% from 1.6(± 0.6) to 0.8(± 0.4)ng/mL (p < 0.001), p2PSA reduced by 55.3% from 18.4(± 8.8) to 8.3(± 5.6)pg/mL (p < 0.001), and phi reduced by 34.2% from 33.7(± 11.9) to 22.4(± 12.5) (p < 0.001). PSA and phi values in the control group remained static over 1year and significantly higher than those in 5ARI group. This study demonstrated p2PSA and phi are reduced by about 55% and 34% in men on 5ARI. A conversion factor of division by 0.66 is needed for phi in men on finasteride to allow the interpretation and use of phi in men on 5ARI.

Re-thinking How We Use Prostate Health Index for African American Men

To assess how the validated Prostate Health Index (PHI) risk stratifications perform with African American (AA) men and establish a threshold PHI value to potentially rule out the need for prostate biopsy. AA men meeting FDA-specified indications for PHI testing (>50 years old, PSA 4-10 and negative DRE) who underwent subsequent biopsy were included. Rates of clinically significant prostate cancer (csPCa, as defined by Gleason score ≥7) across accepted PHI stratifications were recorded. Receiver operator curve (ROC) analysis was undertaken to assess PHI performance to predict csPCa. A phi cutoff providing 90% sensitivity was identified. Among AA men with PSA 4-10 ng/mL, the proportion of men who proceeded to biopsy upon physician recommendation was determined. Two hundred nine patients met primary criteria; 91 (43.5%) of which had csPCA. The area under the curve for PHI predicting csPCa was 0.68 (95% CI: 0.61-0.75). Using a phi threshold of <23.0 to avoid biopsy provided 98.9% sensitivity, 9.3% specificity, and would have avoided 4.7% of biopsies. The proportion of those who proceeded to biopsy upon physician recommendation was 81.8%. PHI demonstrated limited performance in our cohort, with current stratifications featuring misleadingly low cancer detection rates for these men. Furthermore, PHI had limited use to avoid prostate biopsy, as the proposed threshold of 23.0 only allowed 4.7% of men to avoid biopsy. Further work is needed to assess and optimize PHI usage in AA men; nonetheless, it may still have use in increasing compliance with biopsy recommendation.

A Neural Network Model Combining [-2]proPSA, freePSA, Total PSA, Cathepsin D, and Thrombospondin-1 Showed Increased Accuracy in the Identification of Clinically Significant Prostate Cancer

The Prostate Health Index (PHI) and Proclarix (PCLX) have been proposed as blood-based tests for prostate cancer (PCa). In this study, we evaluated the feasibility of an artificial neural network (ANN)-based approach to develop a combinatorial model including PHI and PCLX biomarkers to recognize clinically significant PCa (csPCa) at initial diagnosis. To this aim, we prospectively enrolled 344 men from two different centres. All patients underwent radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/mL. We used an artificial neural network to develop models that can identify csPCa efficiently. As inputs, the model uses [-2]proPSA, freePSA, total PSA, cathepsin D, thrombospondin, and age. The output of the model is an estimate of the presence of a low or high Gleason score PCa defined at RP. After training on a dataset of up to 220 samples and optimization of the variables, the model achieved values as high as 78% for sensitivity and 62% for specificity for all-cancer detection compared with those of PHI and PCLX alone. For csPCa detection, the model showed 66% (95% CI 66-68%) for sensitivity and 68% (95% CI 66-68%) for specificity. These values were significantly different compared with those of PHI (p < 0.0001 and 0.0001, respectively) and PCLX (p = 0.0003 and 0.0006, respectively) alone. Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.

Biology and usefulness of [-2]proPSA as a prognostic marker in CRPC patients.

242 Background: Prostate health index (phi) using -2proPSA (p2PSA), which is a precursor of PSA, has been reported to be useful as a marker for predicting the presence of cancer in the gray zone with a PSA value of 4-10 ng/ml. There is no detailed report on the biology of p2PSA in castration resistant prostate cancer (CRPC) patients and it is unknown. We retrospectively investigated the biology of p2PSA and its usefulness as a marker using CRPC patient's samples. Methods: The study was performed using samples from a prospective study of CRPC patients treated with enzalutamide. We examined 98 pre-enzalutamide treatment serum samples that can measure p2PSA. The samples were collectively measured by Beckman Coulter (Tokyo, Japan). We also examined the correlation between the measurement results of p2PSA and the prognosis of phi and CRPC patients calculated accordingly. This study was approved by the IRB of Gunma University Hospital (IRB 2021-092, 1983). Results: The study population of 98 patients had a median age of 73 years. The median PSA before administration of enzalutamide was 23.8 ng/ml, the median p2PSA was 208.8 pg/ml, and the median phi was 188.0. The median values of each parameter were divided into two groups, and the PSA progression free survival (PSA-PFS) and overall survival (OS) rate were compared by the Kaplan-Meier method. In the study of PSA-PFS, PSA, p2PSA, and phi could not be significant markers. In the OS study, the median OS of the PSA low group was NYR (not yet reached), the high group was 26.8 months, the p2PSA low group was NYR, the high group was 26.8 months, the phi low group was NYR, and the high group was 26.8 months. The OS was significantly better in the low- value group for each parameter (p-values 0.024, 0.034, 0.018, respectively). Conclusions: The biology of p2PSA in CRPC patients has been clarified. Although we couldn't find a clear advantage over PSA, we would like to add a study based on the data of this study.

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy

To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34-2.56), 2.07 (95%CI: 1.50-2.84), 3.26 (95%CI: 2.36-4.48), and 5.06 (95%CI: 3.68-6.97) times as likely to develop PCa (all p < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2-10 ng/mL or 2-20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (phi) at 27-36 (Ptrend < 0.05) or >36 (Ptrend ≤ 0.001). Notably, men with moderate phi (27-36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high phi (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, phi, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887-0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over phi for PCa. The combination of PRS and phi that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA.

Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk.

To evaluate different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI). A total of 322 patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study. The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with International Society of Urological Pathology [ISUP] grade >1). Clinical parameters included age, body mass index, ancestry, and germline mutational status,mpMRI, prostate-specific antigen density (PSAD), Prostate Health Index and urinary markers (Prostate Cancer Associated 3, SelectMdx™ and T2:ERG score) were assessed. Sensitivity (Se) and specificity (Sp) for each marker at their recommended cut-off for clinical practice were calculated. Comparison between diagnoses accuracy of each procedure and scenario was computed using mutual information based and direct effect contribution using a supervised Bayesian network approach. A mpMRI Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 showed higher Se than mpMRI PI-RADS score ≥4 for detection of PCa (82% vs 61%) and for the detection of ISUP grade >1 lesions (96% vs 80%). mpMRI PI-RADS score ≥3 performed better than a PSA level of ≥3 ng/mL (Se 96%, Sp 53% vs Se 91%, Sp 8%) for detection of clinically significant PCa. In case of negative mpMRI results, the supervised Bayesian network approach showed that urinary markers (with the same accuracy for all) and PSAD of ≥0.10 ng/mL/mL were the most useful indicators of decision to biopsy. We found that screening men at high genetic risk of PCa must be based on mpMRI without pre-screening based on a PSA level of >3 ng/mL, to avoid missing too many ISUP grade >1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or a PSAD of ≥0.10 ng/mL/mL when mpMRI was negative increased the detection of ISUP grade >1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from the age of 40 years.

Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)

Prostate-specific antigen (PSA) is the recommended tumor marker for individual screening and follow-up of prostate cancer. This paper reviews main structural and physiological data about prostate specific antigen isoforms: total PSA, free PSA, [-2]proPSA (also named p2PSA). It describes the pre-, per- and post-analytical conditions for these different parameters. It presents the interpretation of results and derived calculated indices (free/total PSA ratio, Prostate Health Index or PHI) for the management of prostate cancer (initial diagnosis and follow-up).

METCAM Is a Potential Biomarker for Predicting the Malignant Propensity of and as a Therapeutic Target for Prostate Cancer.

Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have been suggested for predicting malignant prostatic carcinoma cancer; however, only a few, such as PSA (prostate-specific antigen), Prostate Health Index (PHI), and PCA3, have been approved by the FDA. However, each biomarker has its merits as well as shortcomings. The serum PSA test is incapable of differentiating prostate cancer from BPH and also has an about 25% false-positive prediction rate for the malignant status of cancer. The PHI test has the potential to replace the PSA test for the discrimination of BPH from prostate cancer and for the prediction of high-grade cancer avoiding unnecessary biopsies; however, the free form of PSA is unstable and expensive. PCA3 is not associated with locally advanced disease and is limited in terms of its prediction of aggressive cancer. Currently, several urine biomarkers have shown high potential in terms of being used to replace circulating biomarkers, which require a more invasive method of sample collection, such as via serum. Currently, the combined multiple tumor biomarkers may turn out to be a major trend in the diagnosis and assessment of the treatment effectiveness of prostate cancer. Thus, there is still a need to search for more novel biomarkers to develop a perfect cocktail, which consists of multiple biomarkers, in order to predict malignant prostate cancer and follow the efficacy of the treatment. We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer.