Prostate Cancer Biopsy Research Articles

Nutritional Supplement With Fermented Soy in Men With an Elevated Risk of Prostate Cancer and Negative Prostate Biopsies: General and Oncological Results From the Prospective PRAECAP Trial

Introduction & ObjectivesTo investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer development after a 6-month challenge in men at increased risk of prostate cancer and negative previous biopsies. Materials & MethodsPatients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA > 3 ng/ml, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS) / magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non-parametric one-sided paired Wilcoxon rank sum test, chi-square test and Fisher's exact test. ResultsIn this trial, 94 patients where eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months (p=0.908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (p<0.001) and significantly fewer ISUP≥3 lesions (p=0.02). ConclusionsWe observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa.

Correlation between Prostate-Specific Antigen Levels and Prostate Imaging Reporting and Data System score: A Retrospective Study

Introduction: Prostate cancer is a prevalent and potentially lethal malignancy affecting men worldwide. To enhance early detection and accurate risk stratification, various diagnostic methods have been developed. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis and prostate biopsy in case prostate cancer is suspected. Total prostate-specific antigen (tPSA) is a widely used, first line and acceptable biomarker for prostate cancer screening. Rising tPSA levels cannot be a definitive diagnosis for prostate cancer and further examination is needed. Мagnetic resonance imaging (MRI) is an irreplaceable part of prostate cancer diagnosis. The introduction of Prostate Imaging-Reporting and Data System (PI-RADS) in MRI of prostate gland precises the cases in which performance of target biopsy is needed by classifying suspected prostate lеsions according to the probability of detecting prostate cancer. Objectivе: The objective of this study is to assess the correlation between tPSA levels and PI-RADS scores in patients who underwent MRI of the prostate gland due to elevated tPSA levels. Material and methods: A retrospective study of 374 patients medical records was carried out from January 2019 to June 2023. All patients had tPSA over 4 ng/ml and underwent MRI. Lesions were classified according to PI-RADS v2.1. Results: Patients mean age was 67.8 ± 8.2 years. Mean prostate volume was 52.67 ± 19.6 cc. 87.5 % of the patients had a negative rectal digital exam and 12.5 % had a positive one. tPSA levels ranged from 4.10 to 500 ng/ml. Patients were categorized in four groups according to their tPSA levels: group A with tPSA levels ranging from 4 to 9.9 ng/ml; group B – tPSA from 10 to 19.9 ng/ ml; group C – tPSA from 20 to 39.9 ng/ml; group D – tPSA over 40 ng/ml. MRI and PI-RADS v2 scoring were performed in all patients. 29.4 % of the MRI exams found lesions scored as PI-RADS 3, 47.1 % – as PI-RADS 4 and 22.5 % as PI-RADS 5. There were only 3 cases of lesions categorized as PI-RADS 2 in the study. These patients did not undergo a biopsy and were followed up. 33.9 % of patients in group A were c assified with PI-RADS score 3, 52.3 % – PI-RADS score 4 and 13.8 % – PI-RADS 5. In group B 1.8 %were categorized in PI-RADS score 2, 28.9 % – PI-RADS score 3, 44.7 % were PI-RADS 4 and 24.6 % PI-RADS 5. In group C the majority of patients (47.9 % and 32.6 %) had lesions classified as PI-RADS 4 and 5. In group D most of the patients` lesions – 60.7 %, were categorized as PI-RADS 5. Conclusion: There is a significant correlation between PI-RADS score and serum total PSA levels with a tendency of higher PI-RADS scores as the tPSA level reaches 10 ng/ml. Elevation of tPSa levels over 4 ng/ml requires MRI of the prostate gland and PI-RADS classification as a diagnostic and confirmation tool for further decision making.

Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

Prostate cancer and liquid biopsies: Clinical applications and challenges.

Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm of prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist in effectively screening for prostate cancer, enhancing risk stratification, and determining optimal approaches for treating advanced disease. Consequently, there is a pressing need for improved biomarkers to aid clinicians in decision-making within these contexts. Cell-free DNA and extracellular vesicle analysis have demonstrated promise in diagnosis, prognostication, assessment of treatment responses, and identification of emerging mechanisms of resistance. Nevertheless, obstacles must be addressed before liquid biopsies can be integrated into routine clinical practice. These challenges encompass preanalytical considerations such as sample collection and storage, methods of extracellular vesicle isolation and enrichment, and the need for enhanced interpretation of generated sequencing data. This review provides a comprehensive overview of current clinical opportunities in managing prostate cancer through blood-based liquid biopsy, highlighting the progress made, and acknowledging the challenges that remain. Additionally, we discuss the next steps required for the effective implementation of liquid biopsies in guiding personalized treatment strategies for prostate cancer.

Abstract 213: NEK1-mediated phosphorylation of YAP1 is key to prostate cancer progression

Abstract The key to preventing metastatic castration-resistant prostate cancer (mCRPC) progression is understanding how androgen-sensitive (AS) PCa cells progress to independence and modify accordingly their transcriptional repertoire. We recently identified a novel axis of the Hippo pathway characterized by the sequential kinase cascade induced by androgen deprivation, AR−&amp;gt;mTOR&amp;gt;TLK1B&amp;gt;NEK1&amp;gt;pYAP1-Y407, leading to CRPC adaptation. Phosphorylation of YAP1-Y407 increases upon androgen deprivation therapy (ADT), correlated with increased NEK1 activity, and this is suppressed in a YAP-Y407F mutant. Overexpression of wt-GFP-YAP but not the Y407F SDM resulted in dramatic morphologic changes. In fact, LNCaP expressing wt-YAP were AI whereas the Y407F mutant were AS, and LNCaP expressing wt-GFP-YAP underwent EMT transformation. This, largely reflecting transcriptional differences in both AR-dependent genes (FKBP5, PSA) and some involved in EMT (ZEB1, TWIST, E-CAD); all of which could be effectively reversed with J54-mediated inhibition of TLK1&amp;gt;NEK!&amp;gt;YAP signaling. We found that J54, a pharmacological inhibitor of the TLK1&amp;gt;NEK1&amp;gt;YAP1 nexus led to degradation of YAP1, suggesting that the Y407 phosphorylation is critical for transcriptional activation and stabilization of YAP. Specifically, Nek1-mediated phosphorylation of YAP-Y407 increases its productive interaction with transcriptional activators like TEAD or AR, resulting in its nuclear retention and stabilization. This was later demonstrated by coIP of TEAD4 or the AR with GFP-YAP antiserum, as well as via LUC expression transfections using ARE and Hippo reporter plasmids in LNCaP expressing wt-GFP-YAP or Y407F proteins, as well as by ChIP for key AR-responsive gene promoters. Further, in NEK1 haploinsufficient TRAMP mice we determined reduced YAP1 expression, a key transcriptional activator of CRPC progression, and, if castrated at 12 weeks, the mice failed to show to overt prostate carcinomas, even while displaying reduced E-Cadherin (E-Cad) expression in hyperplastic ductules. Finally, IHC examination of prostate cancer biopsies revealed that pYAP1-Y407 nuclear signal is low in samples of low-grade cancer but elevated in high GS specimens. Citation Format: Damilola M. Olatunde, Ishita Ghosh, Arrigo De Benedetti. NEK1-mediated phosphorylation of YAP1 is key to prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 213.

Topline/Final Diagnostic Inclusion of Relevant Histologic Findings in Surgical Pathology Reporting of Carcinoma in Prostate Biopsies.

As the list of histologic parameters to include in surgical pathology reports of prostate cancer biopsies grows, some pathologists include this information in the microscopic description or summary sections of the report, whereas others include it in the "topline" or final diagnosis section. This prompted us to develop a multi-institutional survey to assess reporting trends among genitourinary (GU) pathologists. A survey instrument was shared among 110 GU pathologists via surveymonkey.com. Anonymized respondent data was analyzed. Eighty-four (76%) participants completed the survey across four continents. Most participants report tumor volume quantitation (88%), number of cores involved (89%), and both Gleason grade and Grade group (93%) in their topline; 71% include percent of pattern 4, with another 16% including it depending on cancer grade; 58% include the presence of cribriform growth pattern 4, with another 11% including it depending on cancer grade. When present, most include extraprostatic extension (90%), prostatic intraductal carcinoma (77%), and perineural invasion (77%). Inclusion of atypical intraductal proliferation (AIP) in the topline diagnosis was cancer grade-dependent, with 74% including AIP in Grade group 1, 61% in Grade group 2, 45% in Grade group 3, 30% in Grade group 4, and 26% in Grade group 5 cancers. Certain histologic features such as Gleason grade and tumor volume/cores involved are frequently included in the topline diagnosis, whereas the incorporation of other findings are more variably included. Prostate biopsy reporting remains a dynamic process with stylistic similarities and differences existing among GU pathologists.

The distinct roles of reinforcement learning between pre-procedure and intra-procedure planning for prostate biopsy

PurposeMagnetic resonance (MR) imaging targeted prostate cancer (PCa) biopsy enables precise sampling of MR-detected lesions, establishing its importance in recommended clinical practice. Planning for the ultrasound-guided procedure involves pre-selecting needle sampling positions. However, performing this procedure is subject to a number of factors, including MR-to-ultrasound registration, intra-procedure patient movement and soft tissue motions. When a fixed pre-procedure planning is carried out without intra-procedure adaptation, these factors will lead to sampling errors which could cause false positives and false negatives. Reinforcement learning (RL) has been proposed for procedure plannings on similar applications such as this one, because intelligent agents can be trained for both pre-procedure and intra-procedure planning. However, it is not clear if RL is beneficial when it comes to addressing these intra-procedure errors.MethodsIn this work, we develop and compare imitation learning (IL), supervised by demonstrations of predefined sampling strategy, and RL approaches, under varying degrees of intra-procedure motion and registration error, to represent sources of targeting errors likely to occur in an intra-operative procedure.ResultsBased on results using imaging data from 567 PCa patients, we demonstrate the efficacy and value in adopting RL algorithms to provide intelligent intra-procedure action suggestions, compared to IL-based planning supervised by commonly adopted policies.ConclusionsThe improvement in biopsy sampling performance for intra-procedure planning has not been observed in experiments with only pre-procedure planning. These findings suggest a strong role for RL in future prospective studies which adopt intra-procedure planning. Our open source code implementation is available here.

Impact of PI-RADS Upgrading Rules on Prostate Cancer Detection and Biopsy Decision-Making.

Impact of PI-RADS Upgrading Rules on Prostate Cancer Detection and Biopsy Decision-Making.

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Detection of PSMA expression on circulating tumor cells by blood-based liquid biopsy in prostate cancer.

For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy. Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood. The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53, and BRCA2 locus. The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.

The risk of prostate cancer diagnosis in men with an elevated PSA but low IsoPSA.

292 Background: IsoPSA is a structure-based serum assay. Initial studies demonstrated that it outperformed total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (i.e., grade group (GG) ≥2) on biopsy. This led to an overall reduction in invasive testing and magnetic resonance imaging (MRI). We sought to compare the risk of csPCa in patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients (n=1578) who underwent IsoPSA testing from November 2016 to August 2022. Data was dichotomized into patients with normal (≤6) and high IsoPSA (&gt;6). We collected the outcomes of any follow-up IsoPSA, prostate biopsy, MRI, and diagnosis of prostate cancer. In the case of multiple follow-up tests, the most recent one was recorded. Results: The median follow-up time of 1578 patients who underwent IsoPSA testing was 24 months (IQR 16-29). Among 541 patients with an initial normal IsoPSA, 60 (11.1%) had a subsequent high IsoPSA, 23 (4.3%) had csPCa on a subsequent biopsy, and 48 (8.9%) had suspicious lesions on MRI (PI-RADS 4-5). Among 1037 patients with an initial high IsoPSA, 366 (35.3%) had csPCa on a subsequent biopsy and 342 (33%) had suspicious lesions on MRI. The sensitivity of IsoPSA to predict csPCa was 94.1%, and its negative predictive value was 89.3%. Conclusions: With 24-month follow-up, 4.3% of patients with normal IsoPSA developed csPCa, suggesting that a low baseline IsoPSA provides durable information about the 2-year risk of csPCa.[Table: see text]

Interim analyses from the PROSPET-BX trial: [G8Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [68Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA&gt;4.0ng/ml; free-to-total PSA ratio &lt;20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [68Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [68Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P&lt;0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax&gt;7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio&gt;2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [68Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [68Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .

Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters. We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated. Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively). We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.

COMPARATIVE ANALYSIS OF MRI, MORPHOLOGICAL AND BIOCHEMICAL FEATURES OF MALIGNANT NEOPLASM OF THE PROSTATE GLAND

Introduction. This article presents a comparative analysis of magnetic resonance imaging (MRI), transrectal ultrasound (TRUS), biopsy and biochemical studies in prostate cancer using histomorphologic grading of the tumor component according to the Gleason score. It has been shown that the level of prostate-specific antigen (PSA) often correlated with the total Gleason score. Materials and methods: In the study, 860 patients with suspected prostate cancer were examined: 530 patients (62 %) were diagnosed with prostate cancer at various stages of development, and 330 patients (38 %) were diagnosed with prostate adenoma. MRI of the prostate was performed in three sections: sagittal, frontal and vertical. The tumor component was assessed using the PI-RADS system. Patients with a PSA level of more than 4.4 ng/ml were selected for the study. The stage of cancer development was determined by the Gleason scale during histological examination. Results of own research: It was found that the MRI diagnostic method was most effective in low and moderately differentiated forms of prostate adenocarcinoma and could also be used to assess the prevalence of the tumor process. The first place among the studied cases (61%) was occupied by stage III prostate cancer, the second place – by stage IV prostate cancer (24%) and the third place – by stage II prostate cancer (15%). Hypoechoic nodular elements were detected in 30.2%, mainly 5–7 by the Gleason score, heterogeneous nodular elements – in 40.1% (8 by the Gleason score), hypointense areas, mainly in the peripheral parts of the gland, were detected in 75.2% (9–10 by the Gleason score). Changes in the vascular pattern depended on the degree of development of the tumor component. Conclusion. Our study revealed a number of features: prostate cancer is mainly characterized by highly differentiated and moderately differentiated forms of adenocarcinoma; in metastasized prostate cancer, a low-grade form of adenocarcinoma is more often detected, which can have an aggressive course and rapid spread of the tumor component.

Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer.

This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3-5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25-4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25-4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11-6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

Urinary volatile organic compounds in prostate cancer biopsy pathologic risk stratification using logistic regression and multivariate analysis models

Urinary volatile organic compounds in prostate cancer biopsy pathologic risk stratification using logistic regression and multivariate analysis models

Adding a Coefficient for Race to the 4Kscore Improves Calibration for Black Men.

Black men face a higher incidence of high-risk prostate cancer (PCa) compared with non-Black men. While the 4Kscore is a widely utilized commercial test for PCa risk assessment, it does not currently account for racial differences. The aim of this study is to describe and validate a prespecified race coefficient for the 4Kscore with the goal of improving the accuracy of this test for Black men. Using data from 85 Black men from the initial US prospective validation study, a race coefficient of 0.6 on the log-odds scale was prespecified. We calculated discrimination, calibration, and clinical utility of the 4Kscore with and without this coefficient for Black race in our primary analysis cohort of 205 Black men undergoing biopsy for PCa in a Veterans Affairs (VA) institution. We performed a sensitivity analysis using a combined cohort from the US prospective validation and the VA studies. The mean probability of high-grade PCa from the 4Kscore in the primary cohort increased from 25% to 37% with race coefficient addition. Incorporating the race coefficient improved 4Kscore's calibration in Black men, with consequent improvements in clinical utility based on decision curve analysis. Model discrimination was maintained (AUC 0.825 vs 0.828, P = .14) in the combined cohort of Black and non-Black men from the US prospective and VA studies and the calibration remained largely unchanged. Incorporating a prespecified coefficient for Black race improved calibration and clinical utility of the 4Kscore among Black men and should be added to the 4Kscore.

Multiparametric bone MRI targeting aides lesion selection for CT-guided sclerotic bone biopsies in metastatic castrate resistant prostate cancer

BackgroundBone biopsies in metastatic castrate-resistant prostate cancer (mCRPC) patients can be challenging. This study’s objective was to prospectively validate a multiparametric bone MRI (mpBMRI) algorithm to facilitate target lesion selection in mCRPC patients with sclerotic bone disease for subsequent CT-guided bone biopsies.Methods20 CT-guided bone biopsies were prospectively performed between 02/2021 and 11/2021 in 17 mCRPC patients with only sclerotic bone disease. Biopsy targets were selected based on MRI, including diffusion-weighted (DWI) and T1-weighted VIBE Dixon MR images, allowing for calculation of the apparent diffusion coefficient (ADC) and the relative fat-fraction (rFF), respectively. Bone marrow with high DWI signal, ADC < 1100 µm2/s and rFF < 20% was the preferred biopsy target. Tumor content and NGS-feasibility was assessed by a pathologist. Prognostic routine laboratory blood parameters, target lesion size, biopsy tract length, visual CT density, means of HU, ADC and rFF were compared between successful and unsuccessful biopsies (p < 0.05 = significant).ResultsOverall, 17/20 (85%) biopsies were tumor-positive and next-generation genomic sequencing (NGS) was feasible in 13/18 (72%) evaluated samples. Neither laboratory parameters, diameter, tract length nor visual CT density grading showed significant differences between a positive versus negative or NGS feasible versus non-feasible biopsy results (each p > 0.137). Lesion mean HU was 387 ± 187 HU in NGS feasible and 493 ± 218 HU in non-feasible biopsies (p = 0.521). For targets fulfilling all MRI selection algorithm criteria, 13/14 (93%) biopsies were tumor-positive and 10/12 (83%) provided NGS adequate tissue.ConclusionsMultiparametric bone MRI can facilitate target lesion selection for subsequent CT-guided bone biopsy in mCPRC patients with sclerotic metastases.Trial registrationCommittee for Clinical Research of the Royal Marsden Hospital registration number SE1220.

Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles

Introduction: Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR.Methods: The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients’ plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients.Results: We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p &amp;lt; 0.0001) tRF-Lys-CTT-5c (p &amp;lt; 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p &amp;lt; 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers—GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76.Conclusion: This study identified two novel EV-enclosed RNA biomarkers–NKX3-1 and GLO1–for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.

Integration of Multiparameter MRI into Conventional Pretreatment Risk Factors to Predict Positive Surgical Margins After Radical Prostatectomy

Introduction/BackgroundPositive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non–nerve-sparing RP. Patients and MethodsIn this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non–nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis. ResultsMultivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens. ConclusionWe developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non–nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management.