Detection Of High-grade Prostate Cancer Research Articles

A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort.

To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.

BioPrev-C - development and validation of a contemporary prostate cancer risk calculator.

To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Abstract A065: Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen

Abstract Background Men of African ancestry (moAA) experience the highest incidence and mortality rates of prostate Cancer (PCa) in the United States, where 1 in 8 men are expected to be diagnosed with the disease in their lifetime. Yet, most biomarkers used in PCa screening today, which are based on prostate specific antigen (PSA), are developed and validated in predominantly White populations with weak or nonexistent validation in moAA, making moAA more likely to be subjected to unnecessary prostate biopsies. To reduce this disparity in PCa detection and management, there is a critical need for new biomarkers with demonstrated usefulness in moAA. We recently showed that plasmacytoma variant translocation 1 (PVT1), exons 4A, 4B, and 9 are overexpressed in the prostate tissues and detected in higher copy numbers in serum of moAA with PCa. In this study, we investigated the predictive power of these potential biomarkers in detecting high-grade PCa across different racial populations. Methodology Forty serum samples from White, Hispanic, and Black men, 50% of whom had PCa with 25% showing high-grade PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using individual PTV1 biomarkers, all pairwise combinations of biomarkers and all three biomarkers. The median area under the receiver operator characteristic curve (AUC) was used to measure the predictive accuracy of each model after a repeated, stratified k-fold cross validation. Model accuracy was first evaluated using data from all races and then for just the Black and Hispanic subpopulation. Our best performing models were compared with PSA as a predictor of PCa. We also evaluated the predictive accuracy of composite models that combined our biomarkers with PSA. Results In predicting high-grade PCa for all races, PSA had a median AUC of 0.58. All our PVT1 biomarkers had an AUC greater than 0.64, which was better than PSA. When PSA and PVT1 exon 4B were combined, the median AUC of PSA increased to 0.67, other PTV1 biomarkers did not improve the AUC of PSA. For the Black and Hispanic subpopulation, PVT1 exon 4A achieved the highest median AUC of 0.92 which was significantly higher than the median AUC of 0.33 achieved with PSA. The model with Exon 4A and Exon 4B as well as all three biomarkers achieved perfect discrimination (AUC of 1.0). We were also able to obtain perfect discrimination when PVT1 exon 4A was combined with PSA (AUC: 1.0). Conclusion Our results show that PVT1 exon 4A is more accurate than PSA in predicting high-grade PCa in Black and Hispanic subpopulations, achieving perfect discrimination when combined with PSA. Significant improvement in PSA’s predictability is observed in all races when combined with PTV1 exon 4B. Thus, PVT1 exon 4A and PVT1 exon 4B may hold the key to reducing disparity in high-grade PCa detection among moAA while improving the predictive accuracy of PSA for the general population. Citation Format: Emmanuel Owusu Asante-Asamani, Dinuka S.H. Sewandi De Silva, Gargi Pal, Michael Liss, Robin Leach, Olorunseun O. Ogunwobi. Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A065.

MP55-16 COMBINATION OF PRE-BIOPSY EXODX TESTING AND mpMRI IMPROVES PREDICTIVE POWER OF HIGH-GRADE PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP55-16 COMBINATION OF PRE-BIOPSY EXODX TESTING AND mpMRI IMPROVES PREDICTIVE POWER OF HIGH-GRADE PROSTATE CANCER Andrew Skomra, Adam Russon, K. Kent Chevli, and Sebastian Caraballo Andrew SkomraAndrew Skomra More articles by this author , Adam RussonAdam Russon More articles by this author , K. Kent ChevliK. Kent Chevli More articles by this author , and Sebastian CaraballoSebastian Caraballo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While PSA screening has been instrumental in decreasing prostate cancer (PCa) mortality, it is also not a reliable test for identification of clinically significant Grade Group 2 (GG2) or higher disease. As such, solitary use of PSA for biopsy decision-making can lead to many unnecessary biopsies, over-detection of indolent cancer, or even missing aggressive cases. The ExoDx Prostate Intelliscore test is a non-invasive risk assessment biomarker tool that has been prospectively evaluated for detection of high grade prostate cancer and can help inform whether to proceed with biopsy. We aimed to evaluate the predictive utility for high-grade PCa of ExoDx and whether there is added value when combined with multi-parametric MRI (mpMRI) at our local institution. METHODS: Records of 109 Medicare patients from University at Buffalo urology providers and affiliates who underwent urine ExoDx testing since 2021 were retrospectively reviewed. Most patients did receive mpMRI imaging and all did eventually proceed with systematic prostate biopsies. Those without a “gray-zone” PSA (2-10 ng/mL) and those with prior prostate biopsies were excluded. We analyzed the sensitivity (SE), specificity (SP), and negative and positive predictive values (NPV and PPV) of the ExoDx biomarker, mpMRI, PSAD, and ExoDx+mpMRI combination technique for detection of all prostate cancers and strictly high-grade prostate cancers (defined as Gleason grade 3+4 or higher). ExoDx Intelliscores>15.6, PIRADS 4 or 5 lesions on MRI, and PSAD’s>.15 were considered high prostate cancer risk values. Multivariate logistic regression modeling adjusting for age, PSA, prostate volume, and family history of PCa was then performed to examine each modality’s ability to predict biopsy-proven cancer. Statistical analysis was performed with SPSS with an α of 0.05. RESULTS: 91 of the 109 patients enrolled met inclusion criteria. Mean age was 70.3 years, median PSA was 4.9. ExoDx had the highest sensitivity overall, but the lowest specificity (Table 1). A positive mRI had the highest specificity and positive predictive value for detecting high-grade prostate cancer between ExoDx and PSAD, though with significant sensitivity trade-off to ExoDx. Logistic regression modeling revealed that having a high ExoDx score or PIRADS 4/5 lesion on MRI were strongly associated with finding high-grade PCa (Table 2): ExoDx OR 6.52 (CI 2.87-15.8, p<.01), PIRADS 4/5 OR 13.41 (CI 3.19-41.22, p<.01), PSAD>.15 OR 2.12 (CI 0.63-4.31, p=.38).Combining the ExoDx biomarker with MRI resulted in the best predictive ability for detecting high-grade cancer with an OR of 18.67 (CI 4.54-68.1, p<.01). CONCLUSIONS: mpMRI outperformed both ExoDx and PSAD for detection of high-grade prostate cancer but with considerable trade-off in sensitivity to ExoDx. Incorporating the ExoDx biomarker with MRI resulted in the best predictive ability, suggesting there may be a synergistic detection effect with combination approach. This data suggests MRI alone may not be sufficient in certain cases and that employing the ExoDx test could provide added benefit for both biopsy decision-making and predictive capability. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e770 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Skomra More articles by this author Adam Russon More articles by this author K. Kent Chevli More articles by this author Sebastian Caraballo More articles by this author Expand All Advertisement PDF downloadLoading ...

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Developing a Multimodal Model for Detecting Higher-Grade Prostate Cancer Using Biomarkers and Risk Factors.

A technique to predict crucial clinical prostate cancer (PC) is desperately required to prevent diagnostic errors and overdiagnosis. To create a multimodal model that incorporates long-established messenger RNA (mRNA) indicators and conventional risk variables for identifying individuals with severe PC on prostatic biopsies. Urinary has gathered for mRNA analysis following a DRE and before a prostatic examination in two prospective multimodal investigations. A first group (n = 489) generated the multimodal risk score, which was then medically verified in a second group (n = 283). The reverse transcription qualitative polymerase chain reaction determined the mRNA phase. Logistic regression was applied to predict risk in patients and incorporate health risks. The area under the curve (AUC) was used to compare models, and clinical efficacy was assessed by using a DCA. The amounts of sixth homeobox clustering and first distal-less homeobox mRNA have been strongly predictive of high-grade PC detection. In the control subjects, the multimodal method achieved a total AUC of 0.90, with the most important aspects being the messenger riboneuclic acid features' PSA densities and previous cancer-negative tests as a nonsignificant design ability to contribute to PSA, aging, and background. An AUC of 0.86 was observed for one more model that added DRE as an extra risk component. Two methods were satisfactorily verified without any significant changes within the area under the curve in the validation group. DCA showed a massive net advantage and the highest decrease in inappropriate costs.

Detection of High-Grade Prostate Cancer With a Super High B-value (4000 s/mm2) in Diffusion-Weighted Imaging Sequences by Magnetic Resonance Imaging

Introduction: High-grade adenocarcinoma of the prostate tends to have denser glandular structures and a prominent desmoplastic reaction, which could be detected by magnetic resonance imaging (MRI) with a super-high b-value in diffusion-weighted imaging (DWI) sequence, to differentiate it from low-grade carcinomas.Objective: To evaluate the diagnostic validity of the diffusion sequence with values ​​of b4000 s/mm2 for the diagnosis of high-grade prostate cancer (Gleason score ≥ 7).Materials and methods: It is a retrospective analytical study of male patients who have undergone a prostate biopsy and count with a prostate MRI with a DWI sequence of a super-high b-value (4000 s/mm2).Results: The sensitivity of the diffusion sequence with b4000 s/mm2 values ​​to classify as positive for prostate cancer was 57.14% as compared to biopsy. The specificity of the diffusion sequence with b4000 s/mm2 values ​​classifying patients with prostate carcinoma as negative was 84.62%. The probability that the diffusion sequence with b4000 s/mm2 values ​​classifies patients with prostate cancer was 80%. The probability that the diffusion sequence with b4000 s/mm2 values ​​does not classify patients with prostate cancer was 64.71%. The proportion of patients adequately classified with prostate cancer using the diffusion sequence with b4000 s/mm2 values ​​was 70.37%.Conclusions: The study shows that using the diffusion sequence with values of b4000 s/mm2 is an optimal value that serves as a tool to be able to decant those high-risk carcinomas with those of low risk; however, it is not a definitive method of diagnosis that could replace the performance of a biopsy. Since the study sample was limited, these results cannot be interpreted as reliable for diagnosing high-grade prostate cancer and should encourage future studies on a larger scale population to obtain significant evidence for a non-invasive diagnostic tool with a better cost-benefit for the patient.

A0484 - Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer

A0484 - Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer

Patterns of finasteride and dutasteride use in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial cohort: effects of socio-demographic factors and a black box warning

Background: Five-alpha reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, have been shown to significantly reduce prostate cancer incidence. However, these agents were also associated with a significant increase in the detection of high-grade prostate cancer leading to an FDA black box warning in 2011. Little is known about the effect of this warning on the subsequent use of these 5-ARIs. The purpose of this analysis was to assess use patterns of finasteride and dutasteride before and after the black box warning. Methods: This cohort study evaluated men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial who had ≥12 months of Medicare Part D coverage from 2008 to 2015, and had not been diagnosed with prostate cancer through 2007. Socio-demographic factors and benign prostatic hyperplasia (BPH) status were ascertained from follow-up questionnaires, while medication use was ascertained from linkage to Medicare Part D claims data. Results: Of 14,833 eligible men, 88.7% identified as non-Hispanic white, 1.7% as African-American, 5.2% as Asian/Pacific Islander and 1.7% as Hispanic. The median age was 72 years; 41.8% reported a BPH diagnosis. Only 13.6% and 4% of the population took finasteride or dutasteride, respectively, at any time from 2008 to 2015. During this period, finasteride use significantly increased from 3.6% to 9.7% and was highest among men with BPH; dutasteride use remained low and decreased from 2.8% to 1.9%. Conclusions: Finasteride use significantly increased after the FDA’s 2011 black box warning, while dutasteride use remained low and steady throughout the study period.

Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort

BackgroundThe risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort. ObjectiveTo estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer. Design, setting, and participantsThis is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history. Outcomes measurements and statistical analysisMultivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories. Results and limitationsA first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57−2.00, p < 0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07−1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01−1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy. ConclusionsMen with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors. Patient summaryIn a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.

Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer

Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895). The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.

MP33-08 GUT MICROBIOTA PROFILE ASSOCIATED WITH HIGH-GRADE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-08 GUT MICROBIOTA PROFILE ASSOCIATED WITH HIGH-GRADE PROSTATE CANCER Kazutoshi Fujita, Makoto Matsushita, Daisuke Motooka, Koji Hatano, Shota Fukae, Norihiko Kawamura, Eisuke Tomiyama, Yujiro Hayashi, Eri Banno, Tetsuya Takao, Shingo Takada, Shinichi Yachida, Takafumi Minami, Masahiro Nozawa, Kazuhiro Yoshimura, Hirotsugu Uemura, Shota Nakamura, and Norio Nonomura Kazutoshi FujitaKazutoshi Fujita More articles by this author , Makoto MatsushitaMakoto Matsushita More articles by this author , Daisuke MotookaDaisuke Motooka More articles by this author , Koji HatanoKoji Hatano More articles by this author , Shota FukaeShota Fukae More articles by this author , Norihiko KawamuraNorihiko Kawamura More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yujiro HayashiYujiro Hayashi More articles by this author , Eri BannoEri Banno More articles by this author , Tetsuya TakaoTetsuya Takao More articles by this author , Shingo TakadaShingo Takada More articles by this author , Shinichi YachidaShinichi Yachida More articles by this author , Takafumi MinamiTakafumi Minami More articles by this author , Masahiro NozawaMasahiro Nozawa More articles by this author , Kazuhiro YoshimuraKazuhiro Yoshimura More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Shota NakamuraShota Nakamura More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The gut microbiota is involved in a variety of diseases that affect the entire body. Diet and body size influence the gut microbiota and are important risk factors for prostate cancer (PCa). However, the association between the gut microbiota and PCa is not well understood. To clarify this association, we analysed the gut microbiota profiles of men with high-grade PCa. METHODS: We collected rectal swab samples of 189 Japanese men who were suspected of PCa based on screening such as MRI or prostate specific antigen (PSA) tests and underwent prostate biopsies from December 2018 to March 2020 at the Osaka University Hospital, Osaka Police Hospital and Osaka General Medical Center. All hospitals are located in Osaka, Japan. RESULTS: One hundred fifty-two Japanese men undergoing prostate biopsies were included in the study and divided into two cohorts: discovery cohort (114 subjects, 72 with cancer and 42 without cancer) and external test cohort (38 subjects, 24 with cancer and 14 without cancer). The gut microbiota in the discovery cohort was compared between two groups, a high-grade PCa group (men with Gleason score 7 or higher PCa) and a negative+low-grade PCa group (men with negative biopsy or Gleason score 6 PCa) using 16S rRNA gene sequencing. Alpha diversity and beta diversity did not differ significantly between the two groups. Using the linear discriminant analysis (LDA) effect size (LEfSe) method, the relative abundance of Rikenellaceae, Alistipes, and Lachnospira were shown to be significantly increased in patients with high-grade PCa (LDA score>2.5). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed a significant increase in five metabolic pathways: multiple amino acid metabolisms, phenylalanine, tryptophan, tyrosine, and histidine (LDA score>2.0). In the receiver operating characteristic (ROC) curve analysis, the index calculated from the amount of 18 bacterial genera, including Lachnospira, which were selected by least absolute shrinkage and selection operator (LASSO) regression, detected high-grade PCa in the discovery cohort with higher accuracy than the prostate-specific antigen (PSA) test (area under the curve (AUC)=0.85 vs. 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs. 0.67). CONCLUSIONS: The results demonstrate an association between a gut microbiota composed of 18 genera and the presence of high-grade PCa in Japanese men. This gut microbiota profile could be a novel useful marker for the detection of high-grade PCa with greater accuracy than the PSA test. Source of Funding: The Japanese Urological Association, Yakult Bio-Science Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e609-e609 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazutoshi Fujita More articles by this author Makoto Matsushita More articles by this author Daisuke Motooka More articles by this author Koji Hatano More articles by this author Shota Fukae More articles by this author Norihiko Kawamura More articles by this author Eisuke Tomiyama More articles by this author Yujiro Hayashi More articles by this author Eri Banno More articles by this author Tetsuya Takao More articles by this author Shingo Takada More articles by this author Shinichi Yachida More articles by this author Takafumi Minami More articles by this author Masahiro Nozawa More articles by this author Kazuhiro Yoshimura More articles by this author Hirotsugu Uemura More articles by this author Shota Nakamura More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Loading ...

Development and internal validation of a prediction model of prostate cancer on initial transperineal template-guided prostate biopsy

BackgroundDue to the invasiveness of prostate biopsy, a prediction model of the individual risk of a positive biopsy result could be helpful to guide clinical decision-making. Most existing models are based on transrectal ultrasonography (TRUS)-guided biopsy. On the other hand, transperineal template-guided prostate biopsy (TTPB) has been reported to be more accurate in evaluating prostate cancer. The objective of this study is to develop a prediction model of the detection of high-grade prostate cancer (HGPC) on initial TTPB.ResultA total of 1352 out of 3794 (35.6%) patients were diagnosed with prostate cancer, 848 of whom had tumour with Grade Group 2–5. Age, PSA, PV, DRE and f/t PSA are independent predictors of HGPC with p < 0.001. The model showed good discrimination ability (c-index 0.886) and calibration during internal validation and good clinical performance was observed through decision curve analysis. The external validation of CPCC-RC, an existing model, demonstrated that models based on TRUS-guided biopsy may underestimate the risk of HGPC in patients who underwent TTPB.ConclusionWe established a prediction model which showed good discrimination ability and calibration in predicting the detection of HGPC by initial TTPB. This model can be used to aid clinical decision making for Chinese patients and other Asian populations with similar genomic backgrounds, after external validations are conducted to further confirm its clinical applicability.

PI-RADS 3 lesions: Does the association of the lesion volume with the prostate-specific antigen density matter in the diagnosis of clinically significant prostate cancer?

IntroductionCurrently, a new subclassification of the Pi-RADS 3 lesions and subgroups is being used: 3a (indolent or low-risk lesions with volume <0.5 ml) and 3b (significant or high-risk lesions with volume ≥0.5 ml). The prostate-specific antigen density (PSAd) has been identified as a diagnostic tool that helps to predict clinically significant prostate cancer (csCaP). The aim of this study is to evaluate the association of the volume of the Pi-RADS 3 lesions and the PSAd in the diagnosis of csCaP. Material and MethodsWe conducted a retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2020. csCaP was defined as Gleason score ≥3 + 4. The population was divided into groups according to the Pi-RADS 3 subclassification and the PSAd value. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 3b lesions for the detection of high-grade prostate cancer, alone and combined with PSAD groups. ResultsIn total, 99 patients with Pi-RADS 3 lesions were included. Forty-three patients were in group 3a and 56, in 3b. Mean PSA was 7.28 ± 2.6 ng/ml. Pi-RADS 3a lesion did not present csCaP but 17.8% of Pi-RADS 3b lesion did. In group 3b with PSAd > 0.15, 62.5% presented csCaP. In those Pi-RADS 3b with PSAd ≤ 0.15, all biopsies were insignificant prostate cancer (isCaP) and 40 biopsies could have been avoided. Considering 3b as positive for csCaP detection, sensitivity was 100%, specificity 48.3%, NPV 17.8%, and PPV 100%. When adding PSAd to group 3b, sensitivity was 100%, specificity was 86.9%, NPV was 62.5%, PPV was 100%. In total, only the subgroup 3b with PSAd > 0.15 presented csCaP and 83.8% biopsies could be avoided. ConclusionsIn this series, the association of the volume of PIRADS 3 lesion and the PSAd improves specificity and PPV contributing to improve the management of csCaP.

SC48 - Clinical utility of 4Kscore, ExosomeDx and SelectMDx and magnetic resonance imaging for the early detection of high-grade prostate cancer

SC48 - Clinical utility of 4Kscore, ExosomeDx and SelectMDx and magnetic resonance imaging for the early detection of high-grade prostate cancer

298 - Clinical utility of biomarkers 4K score, SelectMDx and ExoDx with MRI for the detection of high-grade prostate cancer

298 - Clinical utility of biomarkers 4K score, SelectMDx and ExoDx with MRI for the detection of high-grade prostate cancer

300 - The SelectMDx urinary-biomarker test: Role in the detection of high-grade prostate cancer and in combination with multi-parametric magnetic resonance imaging in a contemporary prospective cohort of biopsy-naïve men

300 - The SelectMDx urinary-biomarker test: Role in the detection of high-grade prostate cancer and in combination with multi-parametric magnetic resonance imaging in a contemporary prospective cohort of biopsy-naïve men

52 - Evaluation of the 4K score and MRI for the detection of high-grade prostate cancer

52 - Evaluation of the 4K score and MRI for the detection of high-grade prostate cancer

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

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

Clinical utility of the exosome based ExoDx Prostate(IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2\u201310\u2009ng/mL

BackgroundThe ExoDx Prostate(IntelliScore) (EPI) test is a non-invasive risk assessment tool for detection of high-grade prostate cancer (HGPC) that informs whether to proceed with prostate biopsy. We sought to assess the impact of EPI on the decision to biopsy in a real-world clinical setting.MethodsWe conducted a prospective, randomized, blinded, two-armed clinical utility study that enrolled 1094 patients with 72 urologists from 24 urology practices. Patients were considered for prostate biopsy at enrollment based on standard clinical criteria. All patients had an EPI test; however, patients were randomized into EPI vs. control arms where only the EPI arm received results for their biopsy decision.ResultsIn the EPI arm (N = 458), 93 patients received negative EPI scores of which 63% were recommended to defer biopsy by the urologist and 74% ultimately deferred. In contrast, 87% of patients with positive EPI scores were recommended to undergo biopsy with a 72% compliance rate to the urologist’s recommendation. This led to detection of 30% more HGPC compared to the control arm, and we estimate that 49% fewer HGPC were missed due to deferrals compared to standard of care (SOC). Overall, 68% of urologists reported that the EPI test influenced their biopsy decision. The primary reason not to comply with EPI results was rising PSA.ConclusionTo our knowledge this is the first report on a PC biomarker utility study with a blinded control arm. The study demonstrates that the EPI test influences the overall decision to defer or proceed with a biopsy and improves patient stratification.