Biopsy Cores Research Articles

Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study

BackgroundTo investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP).MethodsA total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan–Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM).ResultsEnrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan–Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses.ConclusionsHyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.

Environmental Impact of Prostate Magnetic Resonance Imaging and Transrectal Ultrasound Guided Prostate Biopsy

BackgroundReducing low-value clinical care is an important strategy to mitigate environmental pollution caused by health care. ObjectiveTo estimate the environmental impacts associated with prostate magnetic resonance imaging (MRI) and prostate biopsy. Design, setting, and participantsWe performed a cradle-to-grave life cycle assessment of prostate biopsy. Data included materials and energy inventory, patient and staff travel contributed by prostate MRI, transrectal ultrasound guided prostate biopsy, and pathology analysis. We compared environmental emissions across five clinical scenarios: multiparametric MRI (mpMRI) of the prostate with targeted and systematic biopsies (baseline), mpMRI with targeted biopsy cores only, systematic biopsy without MRI, mpMRI with systematic biopsy, and biparametric MRI (bpMRI) with targeted and systematic biopsies. We estimated the environmental impacts associated with reducing the overall number and varying the approach of a prostate biopsy by using MRI as a triage strategy or by omitting MRI. The study involved academic medical centers in the USA, outpatient urology clinics, health care facilities, medical staff, and patients. Outcome measurements and statistical analysisGreenhouse gas emissions (CO2 equivalents, CO2e), and equivalents of coal and gasoline burned were measured. Results and limitationsIn the USA, a single transrectal prostate biopsy procedure including prostate MRI, and targeted and systematic biopsies emits an estimated 80.7 kg CO2e. An approach of MRI targeted cores alone without a systematic biopsy generated 76.2 kg CO2e, a systematic 12-core biopsy without mpMRI generated 36.2 kg CO2e, and bpMRI with targeted and systematic biopsies generated 70.5 kg CO2e; mpMRI alone contributed 42.7 kg CO2e (54.3% of baseline scenario). Energy was the largest contributor, with an estimated 38.1 kg CO2e, followed by staff travel (20.7 kg CO2e) and supply production (11.4 kg CO2e). Performing 100 000 fewer unnecessary biopsies would avoid 8.1 million kg CO2e, the equivalent of 4.1 million liters of gasoline consumed. Per 100 000 patients, the use of prostate MRI to triage prostate biopsy and guide targeted biopsy cores would save the equivalent of 1.4 million kg of CO2 emissions, the equivalent of 700 000 l of gasoline consumed. This analysis was limited to prostate MRI and biopsy, and does not account for downstream clinical management. ConclusionsA prostate biopsy contributes a calculable environmental footprint. Modifying or reducing the number of biopsies performed through existing evidence-based approaches would decrease health care pollution from the procedure. Patient summaryWe estimated that prostate magnetic resonance imaging (MRI) with a prostate biopsy procedure emits the equivalent of 80.7 kg of carbon dioxide. Performing fewer unnecessary prostate biopsies or using prostate MRI as a tool to decide which patients should have a prostate biopsy would reduce procedural greenhouse gas emissions and health care pollution.

Efficacy and safety of the new biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy in the detection of prostate cancer: Study protocol for a randomized controlled trial.

Recent EAU guideline strongly recommended combined targeted biopsy (TBx) with systematic biopsy (SBx) for biopsy naïve patients with suspected multiparametric magnetic resonance imaging (mpMRI) lesions; However, the clinical goal is to find out how to determine the optimal SBx and TBx cores for biopsy in order to maximize the detection of csPCa and minimize the associated defects. This study aims to assess the efficacy and safety of the new biopsy strategy combining 6-core systematic and 3-core MRI- TBx compared to 12-core systematic and 3-core MRI-TBx strategy. This is a single-center, prospectively randomized controlled clinical trial. 280 men meeting inclusion criteria will be recruited and will be randomly allocated to either 6-core systematic plus 3-core MRI-TBx group (Group A) or 12-core systematic plus 3-core MRI-TBx group (Group B). The primary outcome compares the detection rate of PCa and clinically significant prostate cancer(csPCa) between group A and group B. The secondary outcomes compare the participant-reported pain score immediate post biopsy using pain measurement scale; proportion of men with post-biopsy complications and adverse events (Time frame: 7 days post biopsy, 30 days post biopsy); proportion of the men who undergo radical prostatectomy and have cancer upgraded histopathology from the biopsy to the radical prostatectomy. A new biopsy strategy should be developed with the goal of minimizing procedure invasion, our study will provide the results of efficacy and safety of the new biopsy strategy (6-core systematic and 3-core MRI-TBx) in biopsy naïve men with suspicious mpMRI lesion in comparison with 12-core systematic and 3-core MRI-TBx. Chinese Clinical Trial Registry, ChiCTR2200056437; http://www.chictr.org.cn/edit.aspx?pid=151413&htm=4.

Abstract P067: Evaluating the risk of clinically significant prostate cancer in lesions detected on multiparametric MRI of the prostate

Abstract Introduction: Multiparametric Magnetic Resonance Imaging (mpMRI) is a valuable tool in the prostate cancer diagnostic pathway. mpMRI has a negative predictive value (NPV) of approximately 90% for detecting clinically significant prostate cancer (csPCa), defined as the presence of any Gleason Grade (GG) 4 or 5. Lesions detected on mpMRI are scored using the PIRADS scoring system from 1 to 5. PIRADS-3, 4 and 5 lesions are recommended for biopsy. The use of mpMRI to guide prostate biopsy has been shown to be superior to systematic biopsy alone for detecting early csPCa as small lesions can be identified and accurately targeted. We analysed the outcome of targeted biopsy of prostate lesions detected on mpMRI, and systematic biopsy when no lesions were detected, to determine the risk of csPCa based on mpMRI findings. Methods: Men attending our prostate diagnostic pathway were offered mpMRI before biopsy. The criteria for pre-biopsy mpMRI were any man suitable for radical surgery or radiotherapy, plus one or more of PSA > 3, palpable lesion on digital rectal examination, or family history of PCa in a first degree relative (father or brother). mpMRI was performed with a 1.5-Tesla magnet and included T2, DWI and DCE sequences. Men with PIRADS 3, 4, and 5 lesions were offered targeted biopsy with 2-4 biopsy cores per lesion, and men with no lesion on MRI were offered systematic prostate biopsy with 8-16 biopsy cores. Results: 546 targeted lesions were biopsied in 349 men. 159 lesions were PIRADS-3, 226 were PIRADS-4, and 161 were PIRADS-5. 141 men with negative mpMRI had systematic prostate biopsy. Of the PIRADS-3 lesions, 84% were benign, 5% had GG 3, 11% had GG 4 and none had GG 5. Of the PIRADS-4 lesions, 44% were benign, 12% had GG 3, 42% had GG 4, and 2% had GG 5. Of the PIRADS-5 lesions, 23% were benign, 2% had GG 3, 62% had GG 4, and 13% had GG 5. Of the men with no lesion on mpMRI, 9% had GG 3, 4% had GG 4, and none had GG 5. Conclusion: Most men with negative mpMRI or PIRADS-3 lesions have benign tissue on biopsy or early PCa and are unlikely to have csPCa. A decision for biopsy vs PSA monitoring in these men should weigh the risks and benefits of biopsy and should be a shared decision taking into consideration individual risk factors for PCa, age and co-morbidities. Citation Format: Chidi N. Molokwu, Christos Gkikas, Nicola Lee, Joanna Lesniak-Buzon, Faisal Ali, Harry Bardgett. Evaluating the risk of clinically significant prostate cancer in lesions detected on multiparametric MRI of the prostate. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P067.

Chordoma: analysis of 47 fine-needle aspiration biopsy, cytologic imprint, and small biopsy specimens.

Fine-needle aspiration (FNA) and small tissue biopsy of chordoma have been reported in several small series, but no large series exists. We undertook an examination of 47 cases (with concurrent core needle biopsy in a subset) to analyze diagnostic accuracy, cytomorphology, and immunohistochemistry. Our cytopathology files were searched for examples of chordoma with histopathologic verification. FNA biopsy smears and core needle were performed using standard techniques. Forty-seven cases of chordoma were retrieved from 44 patients [M:F; 1.8:1; age range 5-81 years; mean age 55 years]. Twenty-seven presented with primary, 10 with locally recurrent, and 7 with metastatic tumors. Two aspirates were from the appendicular skeleton, 2 from the trunk, 1 from neck lymph node, and 42 aspirates (89%) from axial and peri-axial skeleton and surrounding soft tissues. Four were cytologic touch imprints while the remainder were FNA biopsy specimens. Specific cytologic diagnoses were chordoma/consistent with chordoma (44 cases, 94%), suspicious for chordoma (2), and malignant neoplasm (1). Along with a single case of benign notochordal tumor misdiagnosed as chordoma, our diagnostic accuracy was 91%. Concurrent tissue biopsy was performed in 51% of cases. Immunohistochemical staining of tumor in 29 (62%) cases showed expression of brachyury in 23 of 24 (96%) instances. Cytopathology consisted of cellular smears populated by large cells possessing enormous amounts of vacuolated and non-vacuolated cytoplasm with an abundant background myxoid/chondromyxoid stroma. FNA and small tissue biopsy specimens show a very high degree of diagnostic accuracy in recognition of chordoma.

Predictors of Outcomes in Patients With Clinically Lymph Node Positive Prostate Cancer After Definitive Radiotherapy.

Studies have suggested that benefits of definitive radiotherapy might be limited to specific patients in clinically lymph node positive (cN1) prostate cancer (PC). However, the beneficial subgroup remains to be elucidated. This study aimed to analyze survival outcomes and prognostic factors after definitive radiotherapy and androgen deprivation therapy (definitive RT+ADT) in these patients and to define subgroups of patients who would benefit from definitive RT+ADT the most. A total of 60 patients with cN1 PC treated with definitive RT+ADT in a single tertiary hospital were accrued. Their clinicopathological variables were analyzed and a new subgroup was identified based on statistically significant variables. At a median follow-up of 31 months, ADT duration ≥24 months (p=0.043, HR=0.26) and positive biopsy core ≥75% (p=0.044, HR=5.29) showed significant relationships with distant metastasis-free survival. Overall survival showed significant relationships with ADT duration ≥24 months (p=0.002, HR=0.06) and number of lymph node (LN) metastases ≥4 (p=0.019, HR=7.17). For prognostic subgroup analysis, patients were divided into three risk groups: low-risk group (LN metastases <4 and ADT ≥24 months), high-risk group (LN metastases ≥4 and ADT <24 months), and intermediate-risk group (all remaining cases). Three-year actuarial overall survival rates for the low-, intermediate-, and high-risk groups were 100%, 93.3%, and 45.7%. ADT duration and number of LN metastases were important prognostic factors in patients with cN1 PC receiving definitive RT+ADT, with low-risk cN1 PC patients showing better outcomes than others.

The CAPRA&PDE4D5/7/9 Prognostic Model Is Significantly Associated with Adverse Post-Surgical Pathology Outcomes.

Objectives: To investigate the association of the prognostic risk score CAPRA&PDE4D5/7/9 as measured on pre-surgical diagnostic needle biopsy tissue with pathological outcomes after radical prostatectomies in a clinically low−intermediate-risk patient cohort. Patients and Methods: RNA was extracted from biopsy punches of diagnostic needle biopsies. The patient cohort comprises n = 151 patients; of those n = 84 had low−intermediate clinical risk based on the CAPRA score and DRE clinical stage <cT3. This cohort (n = 84) was investigated for pathology outcomes in this study. RT-qPCR was performed to determine PDE4D5, PDE4D7 and PDE4D9 transcript scores in the cohorts. The CAPRA score was inferred from the relevant clinical data (patient age, PSA, cT, biopsy Gleason, and percentage tumor positive biopsy cores). Logistic regression was used to combine the PDE4D5, PDE4D7 and PDE4D9 scores to build a PDE4D5/7/9_BCR regression model. The CAPRA&PDE4D5/7/9_BCR risk score used was same as previously published. Results: We investigated three post-surgical outcomes in this study: (i) Adverse Pathology (any ISUP pathological Gleason grade >2, or pathological pT stage > pT3a, or tumor penetrated prostate capsular status, or pN1 disease); (ii) any ISUP pathological Gleason >2; (iii) any ISUP pathological Gleason >1. In the n = 84 patients with low to intermediate clinical risk profiles, the clinical-genomics CAPRA&PDE4D5/7/9_BCR risk score was significantly lower in patients with favorable vs. unfavorable outcomes. In univariable logistic regression modeling the genomics PDE4D5/7/9_BCR as well as the clinical-genomics CAPRA&PDE4D5/7/9_BCR combination model were significantly associated with all three post-surgical pathology outcomes (p = 0.02, p = 0.0004, p = 0.04; and p = 0.01, p = 0.0002, p = 0.01, respectively). The clinically used PRIAS criteria for the selection of low-risk candidate patients for active surveillance (AS) were not significantly associated with any of the three tested post-operative pathology outcomes (p = 0.3, p = 0.1, p = 0.1, respectively). In multivariable analysis adjusted for the CAPRA score, the genomics PDE4D5/7/9_BCR risk score remained significant for the outcomes of adverse pathology (p = 0.04) and ISUP pathological Gleason >2 (p = 0.004). The negative predictive value of the CAPRA&PDE4D5/7/9_BCR risk score using the low-risk cut-off (0.1) for the three pathological endpoints was 82.0%, 100%, and 59.1%, respectively for a selected low-risk cohort of n = 22 patients (26.2% of the entire cohort) compared to 72.1%, 94.4%, and 55.6% for n = 18 low-risk patients (21.4% of the total cohort) selected based on the PRIAS inclusion criteria. Conclusion: In this study, we have shown that the previously reported clinical-genomics prostate cancer risk model CAPRA&PDE4D5/7/9_BCR which was developed to predict biological outcomes after surgery of primary prostate cancer is also significantly associated with post-surgical pathology outcomes. The risk score predicts adverse pathology independent of the clinical risk metrics. Compared to clinically used active surveillance inclusion criteria, the clinical-genomics CAPRA&PDE4D5/7/9_BCR risk model selects 22% (n = 8) more low-risk patients with higher negative predictive value to experience unfavorable post-operative pathology outcomes.

The impact of prostate biopsy on erectile and ejaculatory function: A prospective study.

To evaluate the impact on erectile and ejaculatory function following transrectal ultrasound-guided biopsies of the prostate (TRUS-Bx) in sexually active men. Monocentric prospective study from May 2021 to January 2022 of consecutive patients with suspected prostate cancer [elevated prostate specific antigen (PSA) level and/or abnormal digital rectal examination] undergoing TRUS-Bx. The 15-item version of the International Index of Erectile Function (IIEF-15), Premature Ejaculation Diagnostic Tool (PDET) and short form of Male Sexual Health Questionnaire (MSHQ-EjD Short Form) were assessed before, one and three months after TRUS-Bx. The primary endpoint was to evaluate the risk of temporary post-biopsy erectile and/or ejaculatory dysfunctions. The statistical significance was set as p value < 0.05. A total of 276 consecutive patients were included in the study. The median age, PSA and biopsy cores were 65 years (IQR 59-69), 7 ng/ml (IQR 5-9.7) and 16 (IQR 12-16), respectively. We compared the IIEF subdomains before TRUS-Bx vs. one or three months: the erectile function (EF) decreased after one month (p<0.001) but recovered after three months (p=0.833); the Orgasmic Function (OF), the Sexual Desire (SD), the Intercourse Satisfaction (IS), the Overall Satisfaction (OS), and Total IIEF decreased significantly after both one and three months compared to pre-biopsy values (p < 0.05). As for ejaculatory function (EjF), PDET, MSHQ-EjD Short Form 1, 2, 3 and MSHQ-EjD Short Form 4 scores decreased significantly after one month (p < 0.001), but they returned to pre-biopsy values after 3 months: p = 0.538, p = 0.071 and p = 0.098, respectively. Our study proved that EF, assessed through IIEF- 15, and ejaculatory function, assessed through PDET and MSHQ-EjD Short Form, were negatively affected by TRUS-Bx one month after the procedure and recovered after three months. Interestingly, the other IIEF-15 subdomains (OF, SD, IS, OS and Total) resulted as significantly reduced also after 3 months: this issue highlights the importance of carefully considering the indication to TRUS-Bx.

Elevated Circulating Lactate Levels and Widespread Expression of Its Cognate Receptor, Hydroxycarboxylic Acid Receptor 1 (HCAR1), in Ovarian Cancer.

Background: Augmented glycolysis in cancer cells is a process required for growth and development. The Warburg effect provides evidence of increased glycolysis and lactic acid fermentation in cancer cells. The lactate end-product of glycolysis is receiving growing traction for its role as a cell signalling molecule. Ovarian cancer (OvCa) is also characterised by altered glucose metabolism. We aim to explore circulating lactate levels in patients with high-grade serous OvCa (HGSOC) and to elucidate the expression of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in OvCa. Methods: HCAR1 expression was detected in patient biopsy cores using immunohistochemistry, while lactate was measured from whole blood with a Biosen-C line clinic measuring system. Results: We noted significantly elevated lactate levels in OvCa patients (4.3 ± 1.9 mmol/L) compared with healthy controls (1.4 ± 0.6 mmol/L; p < 0.0001), with an AUC of 0.96. The HCAR1 gene is overexpressed in OvCa compared to healthy controls (p < 0.001). Using an OvCa tissue microarray (>75% expression in 100 patients), high protein expression was also recorded across all epithelial OvCa subtypes and ovarian normal adjacent tissue (NAT). Conclusions: Lactate monitoring is a simple, cost-efficient test that can offer point-of-care results. Our data suggest that the potential of circulating lactate as a screening biomarker in OvCa merits further research attention.

A Comparative Study between Transrectal Ultrasound Guided 6-Core and 12-Core Prostate Biopsy for Detection of Prostate Cancer

Background: Prostate cancer is common in urological practice. Diagnosis of prostate cancer depends on biopsy of the prostate. For the last two decade TRUS guided 6 core (sextant) biopsy is being considered as standard for prostate biopsy. Various studies in different countries showed the drawback of sextant biopsy. The debate remains alive on number of biopsy core which is appropriate for obtaining representative tissue. Moreover, more number of needle biopsy may be associated with more complication. Methods: In this hospital based Quasi experimental study, a total of 50 patients were allocated into two groups by purposive sampling technique where 6 core prostate biopsy in one group and 12 core biopsy in another group. Baseline demographic and clinical data were recorded. Post procedural morbidity &amp; histopathological findings were recorded. All the collected data were compiled. Further Statistical analyses of the results were obtained by using Microsoft Xcel, 2010 and web based computer software - Graph Pad Software, 2017. A probability value (p) of less than 0.05 was considered to indicate statistical significance. Results: The baseline characteristics like age, S.PSA, prostate volume &amp; DRE findings were similar in two groups. Cancer detection rate was not significantly different between the 6 core biopsy group and 12 core biopsy group (48% Vs 60%, p=0.395). Dysuria with difficulty in micturition and hematuria after biopsy significantly more in 12 core biopsy group (24% Vs 44% and 32% Vs 60% respectively). Other post procedural complications like fever, perrectal bleeding was found statistically not significant between two groups Conclusion: Trans rectal ultrasound guided 6 core biopsy is equally effective as Trans rectal ultrasound guided 12 core biopsy for detection of prostate cancer.

Intraoperative 3D-US-mpMRI Elastic Fusion Imaging-Guided Robotic Radical Prostatectomy: A Pilot Study.

When performing a nerve-sparing (NS) robotic radical prostatectomy (RARP), cancer location based on multiparametric MRI (mpMRI) is essential, as well as the location of positive biopsy cores outside mpMRI targets. The aim of this pilot study was to assess the feasibility of intraoperative 3D-TRUS-mpMRI elastic fusion imaging to guide RARP and to evaluate its impact on the surgical strategy. We prospectively enrolled 11 patients with organ-confined mpMRI-visible prostate cancer (PCa), histologically confirmed at transperineal fusion biopsy using Koelis Trinity. Before surgery, the 3D model of the prostate generated at biopsy was updated, showing both mpMRI lesions and positive biopsy cores, and was displayed on the Da Vinci robotic console using TilePro™ function. Intraoperative 3D modeling was feasible in all patients (median of 6 min). The use of 3D models led to a major change in surgical strategy in six cases (54%), allowing bilateral instead of monolateral NS, or monolateral NS instead of non-NS, to be performed. At pathologic examination, no positive surgical margins (PSMs) were reported. Bilateral PCa presence was detected in one (9%), four (36%), and nine (81%) patients after mpMRI, biopsy, and RARP, respectively. Extracapsular extension was found in two patients (18%) even if it was not suspected at MRI. Intraoperative 3D-TRUS-mpMRI modeling with Koelis Trinity is feasible and reliable, helping the surgeon to maximize functional outcomes without increasing the risk of positive surgical margins. The location of positive biopsy cores must be registered in 3D models, given the rates of bilateral involvement not seen at mpMRI.

3D-Reconstructed Contact Surface Area and Tumour Volume on Magnetic Resonance Imaging Improve the Prediction of Extraprostatic Extension of Prostate Cancer.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p < 0.001). Multivariable logistic regression analysis showed that the radiological tumour stage (p = 0.001), tumour volume (p < 0.001), prostate CSA (p < 0.001), and tumour CSA (p ≤ 0.001) were independent predictors of pathological EPE. A 3D reconstruction of tumour locations in the prostate improves prediction of extraprostatic extension. Tumours with a higher 3D-reconstructed volume, a higher surface area of tumour in contact with the prostate capsule, and higher surface area of prostate capsule in contact with the tumour are at increased risk of side-specific extraprostatic extension.

Semi-supervised learning from coarse histopathology labels

ABSTRACT Ultrasound imaging is commonly used to guide sampling the prostate tissue in transrectal biopsies, followed by detection of cancer through histopathological analysis and coarse labelling of sampled tissue. Ideally, the procedure should be improved by developing machine learning solutions that can identify the presence of cancer in ultrasound images to guide the biopsy procedure. Training a fully supervised learning model using coarse histopathology labels suffers from weakly annotated data which introduce label noise for each image pixel. To address this challenge, we propose a semi-supervised framework for learning with noisy labels. We leverage a two-component mixture model to cluster the training data into clean and noisy label samples based on their loss values. Then, during the semi-supervised training phase, we utilise the well-known MixMatch algorithm which incorporates consistency regularisation, entropy minimisation, and the Mixup regularisation as well as the cross-entropy loss function for noisy and clean sets, respectively. We evaluate the proposed framework with prostate ultrasound data obtained from 71 subjects, while sampling 264 biopsy cores. We achieve balanced accuracy, sensitivity, and specificity of 78.6%, 80.0%, and 77.1%, respectively. In a detailed comparison study, we demonstrate that our proposed framework outperforms the fully supervised method with state-of-the-art robust loss functions.

Ipsilateral hemigland prostate biopsy may underestimate cancer burden in patients with unilateral mpMRI-visible lesions.

To evaluate the cancer detection rates of reduced-core biopsy schemes in patients with unilateral mpMRI-visible intraprostatic lesions and to analyze the contribution of systematic biopsy cores in clinically significant prostate cancer (csPCa) detection. 212 patients with mpMRI-visible unilateral intraprostatic lesions undergoing MRI/TRUS fusion-guided targeted biopsy (TBx) and systematic biopsy (SBx) were included. Cancer detection rates of TBx + SBx, as determined by highest Gleason Grade Group (GG), were compared to 3 reduced-core biopsy schemes: TBx alone, TBx + ipsilateral systematic biopsy (IBx; MRI-positivehemigland), and TBx + contralateral systematic biopsy (CBx; MRI-negative hemigland). Patient-level and biopsy core-level data were analyzed using descriptive statistics with confidence intervals. Univariable and multivariable logistic regression analysis was conducted to identify predictors of csPCa (≥ GG2) detected in MRI-negative hemiglands at p < 0.05. Overall, 43.4% (92/212) of patients had csPCa and 66.0% (140/212) of patients had any PCa detected by TBx + SBx. Of patients with csPCa, 81.5% had exclusively ipsilateral involvement (MRI-positive), 7.6% had only contralateral involvement (MRI-negative), and 10.9% had bilateral involvement. The csPCa detection rates of reduced-core biopsy schemes were 35.4% (75/212), 40.1% (85/212), and 39.6% (84/212) for TBx alone, TBx + IBx, and TBx + CBx, respectively, with detection sensitivities of 81.5%, 92.4%, and 91.3% compared to TBx + SBx. Reduced-core prostate biopsy strategies confined to the ipsilateral hemigland underestimate csPCa burden by at least 8% in patients with unilateral mpMRI-visible intraprostatic lesions. The combined TBx + SBx strategy maximizes csPCa detection.

Potential Role of Seven Proteomics Tissue Biomarkers for Diagnosis and Prognosis of Prostate Cancer in Urine.

As the currently available tests for the clinical management of prostate cancer (PCa) are still far from providing precise diagnosis and risk stratification, the identification of new molecular marker(s) remains a pertinent clinical need. Candidate PCa biomarkers from the published proteomic comparative studies of prostate tissue (2002-2020) were collected and systematically evaluated. AZGP1, MDH2, FABP5, ENO1, GSTP1, GSTM2, and EZR were chosen for further evaluation in the urine of 85 PCa patients and controls using ELISA. Statistically significant differences in protein levels between PCa and BPH showed FABP5 (p = 0.019) and ENO1 (p = 0.015). A biomarker panel based on the combination of FABP5, ENO1, and PSA provided the highest accuracy (AUC = 0.795) for PCa detection. The combination of FABP5, EZR, AZGP1, and MDH2 showed AUC = 0.889 in PCa prognosis, with 85.29% of the samples correctly classified into low and high Gleason score (GS) groups. The addition of PSA to the panel slightly increased the AUC to 0.914. AZGP1, FABP5, and EZR showed significant correlation with GS, stage, and percentage of positive biopsy cores. Although validation using larger patient cohorts will be necessary to establish the credibility of the proposed biomarker panels in a clinical context, this study opens a way for the further testing of more high-quality proteomics biomarkers, which could ultimately add value to the clinical management of PCa.

Prospective of 18-Core TRUS Biopsy and Detection Rate of Prostate Cancer

Background: A systematic 12-core transrectal ultrasound (TRUS)-guided prostate biopsy is currently recommended for prostate malignancy detection modalities. However, there is limited data about the diagnostic yield of increasing the core number to 18. Objective: To assess the effectiveness of cancer detection and clinical advantages between 12- and 18-core TRUS biopsies. Materials and Methods: The authors conducted a prospective, single-group trial of TRUS biopsies specifically for patients with prostate-specific antigen (PSA) levels between 4.0 and 20.0 ng/mL. Sixty-two consecutive patients were enrolled and received a 12- or an 18-core TRUS biopsy under local anaesthesia. The patients and prostate cancer characteristics, such as serum PSA, free PSA, prostate volume, PSA density, D’Amico risk classification, and Gleason grade group were recorded and analysed. Results: The prostate cancer detection rate using 12 cores for the initial TRUS biopsy was 22.6% (14 patients), while using 18 cores was 24.2% (15 patients). The results were not statistically different (p=0.83). Postoperative complications were two cases of gross haematuria and two case of acute urinary retention, which did not require admission. Infection occurred in two patients and no serious morbidities or mortalities. Conclusion: The present study did not find any significant benefit in increasing the number of biopsy cores from 12 to 18 for the diagnosis of prostate cancer in men with serum PSA levels between 4.0 and 20.0 ng/mL. Keywords: Transrectal prostate biopsy; 12-core; 18-core; Prostate cancer; Cancer detection

Assessing the Role of High-resolution Microultrasound Among Naïve Patients with Negative Multiparametric Magnetic Resonance Imaging and a Persistently High Suspicion of Prostate Cancer

BackgroundMultiparametric magnetic resonance imaging (mpMRI) is an invaluable diagnostic tool in the decision-making for prostate biopsies (PBx). However, a non-negligible proportion of patients with negative MRI (nMRI) may still harbour prostate cancer (PCa). ObjectiveTo assess whether microultrasound (micro-US) can help in substratifying the presence of PCa and clinically significant PCa (csPCa; ie, any Gleason score ≥7 PCa) in patients with nMRI despite a persistently high clinical suspicion of PCa. Design, setting, and participantsA total of 125 biopsy-naïve patients who underwent micro-US–guided PBx with the ExactVu system for a persistently high suspicion of PCa despite nMRI were prospectively enrolled. InterventionThe Prostate Risk Identification using micro-US (PRI-MUS) protocol was used to identify suspicious areas; PBx included targeted sampling of PRI-MUS ≥3 areas and systematic sampling. Outcome measurements and statistical analysisThe primary endpoint was the assessment of micro-US diagnostic accuracy in detecting csPCa. Secondary endpoints included determining the proportion of patients with nMRI who may avoid PBx after micro-US or transrectal US, presence of cribriform and intraductal patterns on biopsy core examination, predictors of csPCa in patients presenting with nMRI, and comparing micro-US–targeted and systematic PBx in identifying csPCa. Results and limitationsConsidering csPCa detection rate, micro-US showed optimal sensitivity and negative predictive value (respectively, 97.1% and 96.4%), while specificity and positive predictive value were 29.7% and 34.0%, respectively. Twenty-eight (22.4%) patients with a negative micro-US examination could have avoided PBx with one (2.9%) missed csPCa. Cribriform and intraductal patterns were found in 14 (41.2%) and four (11.8%) of csPCa patients, respectively. In multivariable logistic regression models, positive micro-US, age, digital rectal examination, and prostate-specific antigen density ≥0.15 emerged as independent predictors of PCa. Targeted and systematic sampling identified 33 (97.1%) and 26 (76.5%) csPCa cases, respectively. The main limitation of the current study is represented by its retrospective single-centre nature on an operator-dependent technology. ConclusionsMicro-US represents a valuable tool to rule out the presence of csPCa among patients with a persistent clinical suspicion despite nMRI. Patient summaryAccording to our results, microultrasound (micro-US) may represent an effective tool for the diagnosis of clinically significant prostate cancer in patients with negative magnetic resonance imaging (nMRI), providing high sensitivity and negative predictive value. Further randomised studies are needed to confirm the potential role of micro-US in the diagnostic pathway of patients with a persistent suspicion of prostate cancer despite nMRI.

T1 Mapping of the Prostate Using Single-Shot T1FLASH: A Clinical Feasibility Study to Optimize Prostate Cancer Assessment.

The aim of this study was to assess the clinical feasibility of magnetic resonance imaging (MRI) T1 mapping using T1FLASH for assessment of prostate lesions. Participants with clinical suspicion for prostate cancer (PCa) were prospectively enrolled between October 2021 and April 2022 with multiparametric prostate MRI (mpMRI) acquired on a 3 T scanner. In addition, T1 mapping was accomplished using a single-shot T1FLASH technique with inversion recovery, radial undersampling, and iterative reconstruction. Regions of interest (ROIs) were manually placed on radiologically identified prostate lesions and representative reference regions of the transitional zone (TZ), benign prostate hyperplasia nodules, and peripheral zone (PZ). Mean T1 relaxation times and apparent diffusion coefficient (ADC) values (b = 50/b = 1400 s/mm 2 ) were measured for each ROI. Participants were included in the study if they underwent ultrasound/MRI fusion-guided prostate biopsy for radiologically or clinically suspected PCa. Histological evaluation of biopsy cores served as reference standard, with grading of PCa according to the International Society of Urological Pathology (ISUP). ISUP grades 2 and above were considered clinically significant PCa for the scope of this study. Histological results of prostate biopsy cores were anatomically mapped to corresponding mpMRI ROIs using biopsy plans. T1 relaxation times and ADC values were compared across prostate regions and ISUP groups. Across different strata, T1 relaxation time, ADC values, and diagnostic accuracy (area under the curve [AUC]) were compared using statistical methods accounting for clustered data. Of 67 eligible participants, a total of 40 participants undergoing ultrasound/MRI fusion-guided prostate biopsy were included. Multislice T1 mapping was successfully performed in all participants at a median acquisition time of 2:10 minutes without evident image artifacts. A total of 71 prostate lesions was radiologically identified (TZ 49; PZ 22). Among those, 22 were histologically diagnosed with PCa (ISUP groups 1/2/3/4 in n = 3/15/3/1 cases, respectively). In the TZ, T1 relaxation time was statistically significantly lower for PCa compared with reference regions ( P = 0.029) and benign prostate hyperplasia nodules ( P < 0.001). Similarly, in the PZ, PCa demonstrated shorter T1 relaxation times versus reference regions ( P < 0.001). PCa also showed a trend toward shorter T1 relaxation times (median, 1.40 seconds) compared with radiologically suspicious lesions with benign histology (median, 1.47 seconds), although statistical significance was not reached ( P = 0.066). For discrimination of PCa from reference regions and benign prostate lesions, T1 relaxation times and ADC values demonstrated AUC = 0.80 and AUC = 0.83, respectively ( P = 0.519). Discriminating PCa from radiologically suspicious lesions with benign histology, T1 relaxation times and ADC values showed AUC = 0.69 and AUC = 0.62, respectively ( P = 0.446). T1FLASH-based T1 mapping yields robust results for quantification of prostate T1 relaxation time at a short examination time of 2:10 minutes without evident image artifacts. Associated T1 relaxation times could aid in discrimination of significant and nonsignificant PCa. Further studies are warranted to confirm these results in a larger patient cohort, to assess the additional benefit of T1FLASH maps in conjunction with mpMRI sequences in the setting of deep learning, and to evaluate the robustness of T1FLASH maps compared with potentially artifact-prone diffusion-weighted imaging sequences.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and prostate cancer grading accuracy

To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway. A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely "standard method"), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method. Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p < 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading. MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.

Current role of systematic biopsy in diagnosis of clinically significant prostate cancer in primary combined MRI-targeted biopsy: a high-volume single-center study

PurposeAdditive systematic biopsy (SB) contributes to prostate cancer (PCA) detection in MRI-targeted biopsy (TB). However, the reasons for this are not yet clear. We compared the performance of TB, SB and the combined approach (CB) in biopsy-naive men to determine the added value of SB for tumor grading and spatial tumor distribution.MethodsTwo hundred and fifty-nine men with PI-RADS 3–5 graded lesions who underwent CB were enrolled. Data were prospectively collected, and cancer detection rates (CDR) were compared at patient and lesion level. Gleason grade up- and down-grading from biopsy to prostatectomy specimens (n = 56; 21.6%) were determined. Clinically significant cancer (csPCA) was defined as Gleason grade ≥ 2.ResultsCDR by CB based on PI-RADS categories 3, 4 and 5 for PCA were 24%, 72% and 98% and 17%, 64% and 96% for csPCA. CB detected more PCA and csPCA than TB (p < 0.001). However, TB showed higher efficiency, defined as CDR per biopsy core, for PCA and csPCA in PI-RADS 4–5 rated patients (p < 0.001). Concordance between biopsy and prostatectomy grading was highest in CB with misdiagnosis of csPCA in 25% of men. TB missed cancer attributed to the index lesion in 10.2% and underestimated csPCA in 7%. In these cases, 76% of csPCA were detected and 85% were upgraded to csPCA by SB in adjacent sectors.ConclusionSB cannot be safely abundant without increased diagnostic uncertainty. When TB missed csPCA, SB detected it close to the MRI-target lesion. Therefore, perifocal biopsies could potentially replace 12-core SB with increased efficiency in taking manageable risks.