12-core Prostate Biopsy Research Articles

Stimulated Raman histology, a novel method to allow for rapid pathologic examination of unprocessed, fresh prostate biopsies.

Delay between targeted prostate biopsy (PB) and pathologic diagnosis can lead to a concern of inadequate sampling and repeated biopsy. Stimulated Raman histology (SRH)is a novel microscopic technique allowing real-time, label-free, high-resolution microscopic images of unprocessed, unsectioned tissue. This technology holds potential to decrease the time for PB diagnosis from days to minutes. We evaluated the concordance of pathologist interpretation of PB SRH as compared with traditional hematoxylin and eosin (H&E) stained slides. Men undergoing prostatectomy were included in an IRB-approvedprospective study. Ex vivo 18-gauge PB cores, taken from prostatectomy specimen, were scanned in an SRH microscope (NIO;Invenio Imaging) at 20 microns depth using two Raman shifts: 2845and 2930 cm-1 , to create SRH images. The cores were then processed as per normal pathologic protocols. Sixteen PB containing a mix of benign and malignant histology were used as an SRH training cohort for four genitourinary pathologists, who were then tested on a set of 32 PBs imaged by SRH and processed by traditional H&E. Sensitivity, specificity, accuracy, and concordance for prostate cancer (PCa)detection on SRH relative to H&E were assessed. The mean pathologist accuracy for the identification of any PCa on PB SRH was 95.7%. In identifying any PCa or ISUP grade group2-5 PCa, a pathologist was independently able to achieve good and very good concordance (κ: 0.769 and 0.845, respectively; p < 0.001). After individual assessment was completed a pathology consensus conference was held for the interpretation of the PB SRH; after the consensus conference the pathologists' concordance in identifying any PCa was also very good (κ: 0.925, p < 0.001; sensitivity 95.6%; specificity 100%). SRH produces high-quality microscopic images that allow for accurate identification of PCa in real-time without need for sectioning or tissue processing. The pathologist performance improved through progressive training, showing that ultimately high accuracy can be obtained. Ongoing SRH evaluation in the diagnostic and treatment setting hold promise to reduce time to tissue diagnosis, while interpretation by convolutional neural network may further improve diagnostic characteristics and broaden use.

PD15-06 SYSTEMATIC PROSTATE BIOPSY WITH INSUFFICIENT BIOPSY CORE NUMBER AT DIAGNOSIS LEADS PSA FAILURE AFTER BRACHYTHERAPY AS MONOTHERAPY FOR CLINICAL STAGE T1C PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023PD15-06 SYSTEMATIC PROSTATE BIOPSY WITH INSUFFICIENT BIOPSY CORE NUMBER AT DIAGNOSIS LEADS PSA FAILURE AFTER BRACHYTHERAPY AS MONOTHERAPY FOR CLINICAL STAGE T1C PROSTATE CANCER Yu Ozawa, Sunao Nohara, Ken Nakamura, Seiya Hattori, Yasuto Yagi, Toru Nishiyama, Atsunori Yorozu, Tetsuo Monma, and Shiro Saito Yu OzawaYu Ozawa More articles by this author , Sunao NoharaSunao Nohara More articles by this author , Ken NakamuraKen Nakamura More articles by this author , Seiya HattoriSeiya Hattori More articles by this author , Yasuto YagiYasuto Yagi More articles by this author , Toru NishiyamaToru Nishiyama More articles by this author , Atsunori YorozuAtsunori Yorozu More articles by this author , Tetsuo MonmaTetsuo Monma More articles by this author , and Shiro SaitoShiro Saito More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003262.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: According to the American Urological Association (AUA) guideline, systematic 10–12-core biopsy is optimal for detecting clinical stage T1c (cT1c) prostate cancer (PCA) and also for obtaining higher pathological concordance. Smaller number of prostate biopsy (PB) cores can underestimate pathological characteristics of PCA. This study reviews association between number of biopsy cores at diagnosis and clinical outcomes after low dose rate permanent seed implantation brachytherapy with iodine-125 (LDR) monotherapy. METHODS: This single-institution retrospective study included 542 cT1c PCA with Gleason score 3+3=6 or 3+4=7 treated between September 2003 and September 2014 with LDR monotherapy without hormonal therapy. Local extent of disease was evaluated by digital rectal examination and pelvic MRI. All specimens of ultrasound guided trans-rectal or trans-perineal systematic PB were reviewed by urological pathologists in our institute. We statistically analyzed with Kaplan-Meier and compared rate of biochemical-recurrence (BCR)-free survival, using the Phoenix definition, between adequate (≥10 biopsy cores, N=397) and inadequate (≤9 biopsy cores, N=144) biopsy groups. Possible risk factors for BCR, such as PSA, Gleason score, biopsy core number and positive biopsy core rate, were analyzed. RESULTS: The median age was 66 (38–87) years old and median follow up period was 10.6 (1.0–18.5) years. The median number of biopsy cores was 12 (4–46). In the adequate biopsy group, more patients had Gleason score 3+4=7 (31% vs. 15%, p<0.01). The 5- and 10-year rates of BCR-free survival rates in the adequate biopsy group were 98.7% and 96.9%, respectively, while those in the inadequate biopsy group were 98.6% and 95.6%, respectively. BCR-free survival rate was significantly higher than in the inadequate biopsy group (p <0.05). In multivariate analysis, biopsy core number ≥10 (Hazard ratio; HR 2.58, p<0.02) and Gleason score 3+4=7 (HR 3.26, p<0.01) were the significant factors for BCR. CONCLUSIONS: Systematic PB with sufficient core number greater than 9 leads to lower BCR in LDR monotherapy. Number of biopsy cores on PB might be an important factor for treatment outcomes. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e420 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yu Ozawa More articles by this author Sunao Nohara More articles by this author Ken Nakamura More articles by this author Seiya Hattori More articles by this author Yasuto Yagi More articles by this author Toru Nishiyama More articles by this author Atsunori Yorozu More articles by this author Tetsuo Monma More articles by this author Shiro Saito More articles by this author Expand All Advertisement PDF downloadLoading ...

Is systematic prostate biopsy an overkill in metastatic prostate carcinoma ? A prospective validation.

To assess the efficacy of 2-core prostate biopsy in advanced prostate cancer patients. This included a retrospective analysis of 12-core prostate biopsies and a prospective validation that a reduced number of cores are sufficient for histopathological diagnosis. The first phase analyzed retrospective data from 12-core prostate biopsies between January 2013 and 2018. In the second phase, from January 2018 to January 2022, in a prospective setting, patients with PSA > 75ng/dl underwent bone scans first. Those with positive bone scans underwent a 2-core biopsy. Cancer detection rate and complications were analyzed to validate the findings of the first phase. In the retrospective analysis, the number of positive cores in metastatic disease was 12 in 93 (73.8%), 11 in 14 (11.1%), and 10 in 7 (5.6%) patients. Using probability analysis, 94% of patients with metastasis could be detected with a single core and 97.8% with a 2-core biopsy. In the prospective analysis, 52 patients with PSA > 75 were enrolled. 3/52 (5.7%) patients had a negative bone scan. 49 were assigned for 2-core biopsy, out of which 48 (97.9%) had a positive result. One patient underwent a repeat 12-core biopsy. The prospective cohort's complications (p = 0.003) and pain score (p = 0.03) were lower compared to patients who underwent standard 12-core biopsies during phase one of the study period. A 2-core biopsy is adequate in almost all patients with metastatic prostate cancer with PSA > 75, and this avoids excess complications and morbidity associated with a systematic 12-core prostate biopsy.

Measuring cancer burden in prostatic needle core biopsies: simplified assessments outperform complex measurements in assessing outcome: evidence to assist pathologist efficiency and minimize datasets.

The optimal method of measuring cancer extent in prostate cancer (PCa) biopsies is unknown. Nine hundred eighty-one men with clinically localised PCa managed conservatively were reviewed with follow up. The number of positive cores (NPC), the Maximum Cancer Length in a core (MCL), Total Cancer Length (TCL), and percentage of positive cores (%+cores) was calculated and univariate and multivariate analysis performed using prostate-specific antigen (PSA), T-stage, and Gleason score. The presence of stromal gaps (SG) was recorded. Univariate models were run where SG made a difference to the MCL. All variables showed significant association with PCa death in univariate models. In multivariate models, incorporating PSA, T-stage, and Gleason score, only %+cores was a significant predictor of outcome, with a 10% increase in %+cores resulting in a hazard ratio (HR) of 1.07 (likelihood-ratio test P > Χ2 =0.01). There were 120 patients where SG made a difference to the MCL and a total of 20 events in this group. Including SG, on univariate analysis the median MCL was 10 mm and HR was 1.16 (P=0.007), not including SG, the median MCL was 6 mm and HR was 1.23 (P=6.3 × 10-4 ). Inclusion or exclusion of SG made no significant difference to TCL as a predictor of outcome. Cancer extent is a strong predictor of PCa death but only %+cores added to the multivariate model. Expressed as a fraction of NPC/total number of cores, this is the simplest method of assessment, which we favour over more complicated methods in nontargeted biopsies.

Comparison of intrarectal heated lidocaine gel and periprostatic nerve block for pain control in transrectal ultrasound-guided prostate biopsy: A randomized controlled non-inferiority trial.

To investigate whether intrarectal local anesthesia with heated lidocaine gel (IRLAH) is non-inferior to periprostatic nerve block (PNB) for reducing pain in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy. We performed a randomized controlled non-inferiority trial with 100 participants who underwent systematic TRUS-guided, 12-core prostate biopsy from August 2019 to July 2020. These participants were randomly assigned to a group receiving intrarectal local anesthesia with 20mL of heated (40°C) 2% lidocaine gel (n=50) or PNB (n=50). The primary outcome was a pain score on a 0-10 visual analogue scale (VAS) at four time points with the non-inferiority margin of 1; VAS-1: during local anesthesia application; VAS-2: during probe insertion; VAS-3: during biopsy; VAS-4: 30minutes after the procedure. The secondary outcome included complications during and after the procedure. The IRLAH group (0.1) met non-inferiority as well as superiority criteria for mean VAS-1 score vs. the PNB group (2.33) (P<0.001), as the difference (95% confidence interval [CI]) between the two groups was-2.23 (-2.66 to-1.79) and the upper bound of the 95% CI were both below the prespecified non-inferiority margin and below zero. For mean VAS-3 score, the difference (95% CI) was 0.3 (-0.38 to 0.98) and the upper bound of the 95% CI did not exceed the predefined non-inferiority margin indicating that IRLAH was non-inferior (IRLAH group, 3.44; PNB group, 3.14). Also, non-inferiority was shown for pain scores at VAS-2 and VAS-4. There were no significant differences in complications. IRLAH is a noninvasive and non-inferior alternative to PNB for pain control in TRUS-guided prostate biopsy without increased risk of complications.

RIPK2 as a prognostic biomarker and predictor of aggressive prostate cancer.

211 Background: Receptor-Interacting Protein Kinase 2 (RIPK2) has been known to play a significant role in inflammation and anti-microbial response via the NF-KB pathway. Recently, RIPK2 was also shown to stabilize and activate c-Myc, a molecule implicated in the progression of various malignancies including prostate cancer (PCa). Our study aims to determine the prognostic value of RIPK2 expression in PCa using immunohistochemistry (IHC) analysis of biopsy specimens with special focus on a predominantly African American (AA) cohort. Methods: Eligible patients aged ≥18 years diagnosed with PCa at the Washington DC VA Medical Center were randomly selected and retrospectively grouped into indolent, locally advanced, and metastatic disease categories and stratified by age, ethnicity, AJCC stage, PSA and Gleason score at diagnosis. Representative tissue from prostate core biopsy, transurethral resection, or radical prostatectomy was analyzed for each patient. RIPK2 expression and intensity were assessed by IHC and graded by two independent pathologists by the following scale: 0 (no cytoplasmic staining), 1+ (weak cytoplasmic staining similar to benign prostatic tissue), 2+ (moderate cytoplasmic staining), and 3+ (strong cytoplasmic staining). The primary endpoint was RIPK2 expression by disease group, and key secondary outcomes were RIPK2 association with Gleason score, PSA at diagnosis, age and race. Fisher’s exact test was used to evaluate statistical significance of the association between RIPK2 expression level and disease category. Results: A total of 89 patients were selected for analysis, of which 75 (84.3%) were AA. All tumors had at least 1+ level RIPK2 expression and there was a highly significant difference in RIPK2 expression according to disease severity (p &lt; 0.001). Stratified RIPK2 expression was 1.53, 1.83, and 2.28 in the indolent, locally advanced, and metastatic groups respectively. We observed a significant directly proportional correlation between RIPK2 expression and a higher PSA level (p= 0.0021), Gleason score (p&lt; 0.001), higher age (p= 0.0276), and AJCC stage (p&lt; 0.001) at the time of diagnosis. Mean RIPK2 expression was 1.81 in AA patients and 2.15 in White patients (p= 0.0332). Conclusions: PCa is the most prevalent cancer in US males and there is an urgent need for more accurate biomarkers that can predict disease severity and suggest actionable targeted therapy. In this retrospective analysis, we confirm that higher RIPK2 expression is associated with more advanced PCa. We extend these findings to a predominantly AA cohort, which may promote improvements in personalized medicine for this population at higher risk for PCa if RIPK2-targeting drugs such as Ponatinib can be utilized.

Feasibility and preliminary clinical tolerability of low-field MRI-guided prostate biopsy.

We evaluate the clinical feasibility of a portable, low-field magnetic resonance imaging (MRI) system for prostate cancer (PCa) biopsy. A retrospective analysis of men who underwent a 12-core systematic transrectal ultrasound-guided prostate biopsy (SB) and a low-field MRI guided transperineal targeted biopsy (MRI-TB). Comparison of the detection of clinically significant PCa (csPCa) (Gleason Grade [GG] ≥ 2) by SB and low field MRI-TB, stratified by Prostate Imaging Reporting & Data System (PI-RADS) score, prostate volume, and prostate serum antigen (PSA) was performed. A total of 39 men underwent both the MRI-TB and SB biopsy. Median (interquartile range [IQR]) age was 69.0 (61.5-73) years, body mass index (BMI) was 28.9 kg/m2 (25.3-34.3), prostate volume was 46.5 cc (32-72.7), and PSA was 9.5 ng/ml (5.5-13.2). The majority (64.4%) of patients had PI-RADS ≥ 4 lesions and 25% of lesions were anterior on pre-biopsy MRII. Cancer detection rate (CDR) was greatest when combining SB and MRI-TB (64.1%). MRI-TB detected 74.3% (29/39) cancers. Of which, 53.8% (21/39) were csPCa while SB detected 42.5% (17/39) csPCa (p = 0.21). In 32.5% (13/39) of cases, MRI-TB upstaged the final diagnosis, compared to 15% (6/39) of cases in which SB upstaged the final diagnosis (p = 0.11). Low-field MRI-TB is clinically feasible. Although future studies on the accuracy of MRI-TB system are needed, the initial CDR is comparable to those seen with fusion-based prostate biopsies. A transperineal and targeted approach may be beneficial in patients with higher BMI and anterior lesions.

Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2.

Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression.

Comparison of Transrectal Ultrasonography-Guided Prostate Biopsies Analgesia's; Rectal Lidocaine Gel Versus Sandwich Anesthesia (Transurethral Plus Transrectal Lidocaine Gel Administration): A Double-Blind, Randomized, Controlled and Prospective Study.

We aimed to evaluate the effectiveness of the additive transurethral anesthetic agent to transrectal anesthetic agent. Transrectal ultrasound-guided 12 core prostate biopsy planned, 237 patients included in our study. The patients randomly divided into two groups. Group 1 (n=113): Only transrectal 2% lidocaine, Group 2 (n=124): Transrectal + Transurethral(Sandwiches) lidocaine gel given to the patients 10 min before the procedure as anesthesia. Immediately after the biopsy, the patient questioned about the level of pain he felt during the needle entry. The evaluation measured by the VAS score. Immediately after biopsy satisfaction rate with the procedure and if rebiopsy was required, acceptance was scored between 1 and 4. The two groups compared statistically. The mean VAS score of Group 1 and Group 2 was 4.88±1.89 and 3.77±1.83, respectively. The pain level of Group 2 was lower than Group 1' pain level. The difference between the two groups was considered statistically significant (p<0.001). The patient satisfaction rates of Group 1 and Group 2 found to be 2.45±0.71 and 2.78±0.66, and the acceptance rate of rebiopsy was 2.81±0.69 and 3.02±0.51, respectively. The patient satisfaction rate and acceptance rate of the rebiopsy of Group 2 were higher than Group 1. Patient satisfaction level (p<0.001) and rebiopsy acceptance rate (p=0.014) between the two groups found to be statistically significant. In the TRUS-guided prostate biopsies, sandwich anesthesia is a cheap, convenient, tolerable, and effective method.

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.

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.

MRI-targeted biopsy cores from prostate index lesions: assessment and prediction of the number needed

BackgroundMagnetic resonance imaging (MRI) is used to detect the prostate index lesion before targeted biopsy. However, the number of biopsy cores that should be obtained from the index lesion is unclear. The aim of this study is to analyze how many MRI-targeted biopsy cores are needed to establish the most relevant histopathologic diagnosis of the index lesion and to build a prediction model.MethodsWe retrospectively included 451 patients who underwent 10-core systematic prostate biopsy and MRI-targeted biopsy with sampling of at least three cores from the index lesion. A total of 1587 biopsy cores were analyzed. The core sampling sequence was recorded, and the first biopsy core detecting the most relevant histopathologic diagnosis was identified. In a subgroup of 261 patients in whom exactly three MRI-targeted biopsy cores were obtained from the index lesion, we generated a prediction model. A nonparametric Bayes classifier was trained using the PI-RADS score, prostate-specific antigen (PSA) density, lesion size, zone, and location as covariates.ResultsThe most relevant histopathologic diagnosis of the index lesion was detected by the first biopsy core in 331 cases (73%), by the second in 66 cases (15%), and by the third in 39 cases (9%), by the fourth in 13 cases (3%), and by the fifth in two cases (<1%). The Bayes classifier correctly predicted which biopsy core yielded the most relevant histopathologic diagnosis in 79% of the subjects. PI-RADS score, PSA density, lesion size, zone, and location did not independently influence the prediction model.ConclusionThe most relevant histopathologic diagnosis of the index lesion was made on the basis of three MRI-targeted biopsy cores in 97% of patients. Our classifier can help in predicting the first MRI-targeted biopsy core revealing the most relevant histopathologic diagnosis; however, at least three MRI-targeted biopsy cores should be obtained regardless of the preinterventionally assessed covariates.

Comparison of systematic randomized 12-core transrectal ultrasonography-guided prostate biopsy with magnetic resonance imaging-transrectal ultrasonography fusion-targeted prostate biopsy.

We aimed to compare the complications and pathological outcomes between systematic 12-core transrectal ultrasonography guided prostate biopsy (TRUS-PB) and magnetic resonance imaging-TRUS fusion targeted prostate biopsy (MRI-TRUS FTPB). We examined 10,901 patients who underwent prostate biopsy from May 2003 to December 2017 retrospectively. Among them, 10,325 patients underwent 12-core TRUS-PB and 576 patients underwent MRI-TRUS FTPB. The clinicopathological features and complications in both groups were compared. After propensity score matching, there were no significant differences in the clinical features and complication rates between both groups (P > .05). In the multivariate analyses, the prostate volume was shown to be the only significant predictor of overall complications, infectious complications, bleeding related complications, and Clavien-Dindo grade ≥ 2 complications after prostate biopsy (P < .001). The present study demonstrates the safety of MRI-TRUS FTPB in terms of complications, compared with that of TRUS-PB. Although the combination of MRI-TRUS FTPB and 12-core TRUS-PB provides enhanced diagnostic power, MRI-TRUS FGB alone could provide a reasonable diagnostic value for prostate cancer if the apparent diffusion coefficient suspicious grade of prostate cancer is ≥4. When the Likert suspicious grade of prostate cancer on the apparent diffusion coefficient map of multiparametric MRI was 3, 13.9% (27/194) of the patients were diagnosed with clinically significant prostate cancer (csPCa); 44.4% (12/27) of them were confirmed as csPCa at the MRI-targeted cores. When the apparent diffusion coefficient suspicious grade was ≥4, 43.0% (108/251) were diagnosed with csPCa; 76.8% (83/108) of them were confirmed to have csPCa at the MRI-targeted cores.

Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters

BackroundAccurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas.MethodsTwenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied.ResultsIn total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson’s test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein.ConclusionIn this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.

Artificial intelligence system shows performance at the level of uropathologists for the detection and grading of prostate cancer in core needle biopsy: an independent external validation study

AbstractAccurate diagnosis and grading of needle biopsies are crucial for prostate cancer management. A uropathologist-level artificial intelligence (AI) system could help make unbiased decisions and improve pathologists' efficiency. We previously reported an artificial neural network-based, automated, diagnostic software for prostate biopsy, DeepDx® Prostate (DeepDx). Using an independent external dataset, we aimed to validate the performance of DeepDx at the levels of prostate cancer diagnosis and grading and evaluate its potential value to the general pathologist. A dataset composed of 593 whole-slide images of prostate biopsies (130 normal and 463 adenocarcinomas) was assembled, including their original pathology reports. The Gleason scores (GSs) and grade groups (GGs) determined by three uropathology experts were considered as the reference standard. A general pathologist conducted user validation by scoring the dataset with and without AI assistance. DeepDx was accurate for prostate cancer detection at a similar level to the original pathology report, whereas it was more concordant than the latter with the reference GGs and GSs (kappa/quadratic-weighted kappa = 0.713/0.922 vs. 0.619/0.873 for GGs and 0.654/0.904 vs. 0.576/0.858 for GSs). Notably, it outperformed the original report, especially in the detection of Gleason patterns 4/5, and achieved excellent agreement in quantifying the Gleason pattern 4. When the general pathologist used AI assistance, the concordance of GG between the user and the reference standard increased (kappa/quadratic-weighted kappa, 0.621/0.876 to 0.741/0.925), while the average slide examination time was substantially decreased (55.7 to 36.8 s/case). Overall, DeepDx was capable of making expert-level diagnosis in prostate core biopsies. In addition, its remarkable performance in detecting high-grade Gleason patterns and enhancing the general pathologist's diagnostic performance supports its potential value in routine practice.

Correlation of digital rectal examination and serum prostate-specific antigen levels for detection of prostate cancer: Retrospective analysis results from a tertiary care urology center.

The objective of our study was to evaluate the detection rate of prostate cancer by digital rectal examination (DRE) and serum prostate-specific antigen (PSA) levels followed by standard 12-core transrectal ultrasound (TRUS)-guided prostate biopsy. After screening of patients presenting with lower urinary tract symptoms (LUTS) using DRE and serum PSA level, we enrolled patients for TRUS-guided 12-core prostate biopsy. Indications included PSA level ≥4 ng/ml and/or suspicious DRE findings. A retrospective analysis was done to find out the correlation between suspicious rectal examination and various serum PSA levels in detection of cancer prostate. A total of 847 patients were screened for cancer prostate during our study period (May 2012-February 2020). Among them, 823 patients who underwent prostate biopsy were analyzed. Prostate cancer was detected in 330 cases (40.09%). Mean age of patient (years) with and without prostate cancer was 66.25 ± 9.45 and 64.3 ± 8.96 years, respectively. Median value of serum PSA in patients positive for cancer was 33 ± 260 ng/ml compared to patients without cancer, who had a median value of 9 ± 64 ng/ml (P-value of <0.0001). The detection rate of cancer based on suspicious DRE findings irrespective of PSA was 52.18% (251/481), compared to 45.46% (311/684) using a PSA cut-off of ≥4.0 ng/ml alone. Among 330 patients with positive biopsy, 19 (5.75%) had a PSA level <4 ng/ml and they were identified based on suspicious DRE alone. Suspicious DRE was significantly associated with detection of prostate cancer across all PSA levels. Patients with PSA <4 can harbor prostate malignancy and such cases can be detected by use of DRE in screening of all patients with LUTS.

Use of Prospective Multiplex Immunohistochemistry to Redefine Tissue Pathways of Diagnostic Core Biopsy of Prostate.

The incidence of prostatic cancer in the United Kingdom has increased over 40% in the past 30 years. The majority of these cancers are diagnosed by core biopsy, posing a considerable strain on a service that struggles to recruit sufficient histopathologists. The current methodology for tissue diagnosis has a significant false-negative rate, small false-positive rate, and a proportion of indeterminate diagnoses. Therefore, this area presents an opportunity both to improve diagnostic quality and to reduce the burden on resources. We investigated streamlining tissue pathways by increasing the utilization of readily available resources to reduce the burden on scarce resources and improve the accuracy of diagnosis. This involved applying prospective multiplex immunohistochemistry (IHC) using 4 different markers (CK5, p63, racemase, and Ki-67) and 2 chromogens. We conducted a prospective study using over 8000 cores and 3 consultant histopathologists. The pathologists assessed each core using either conventional stains (hematoxylin and eosin) only or multiplex IHC only. The results of this assessment were later compared with the overall assessment made for the final histologic diagnosis. Results show that IHC alone has a positive predictive value of 98.97% and a negative predictive value of 99.91%, while hematoxylin and eosin alone has a positive predictive value of 94.21% and negative predictive value of 99.07%, demonstrating improved diagnostic accuracy. When assessed against the use of on-demand IHC, prospective IHC improves turn-around-times, reduces indeterminate diagnoses, improves pathologist’s accuracy and efficiency and, in overall terms, is cost-effective. In addition, it is possible to structure these tests within the routine of a diagnostic service with little impact on the overall capacity of the laboratory.

Prediction of Adverse Pathology at Radical Prostatectomy in Grade Group 2 and 3 Prostate Biopsies Using Machine Learning.

There is ongoing clinical need to improve estimates of disease outcome in prostate cancer. Machine learning (ML) approaches to pathologic diagnosis and prognosis are a promising and increasingly used strategy. In this study, we use an ML algorithm for prediction of adverse outcomes at radical prostatectomy (RP) using whole-slide images (WSIs) of prostate biopsies with Grade Group (GG) 2 or 3 disease. We performed a retrospective review of prostate biopsies collected at our institution which had corresponding RP, GG 2 or 3 disease one or more cores, and no biopsies with higher than GG 3 disease. A hematoxylin and eosin-stained core needle biopsy from each site with GG 2 or 3 disease was scanned and used as the sole input for the algorithm. The ML pipeline had three phases: image preprocessing, feature extraction, and adverse outcome prediction. First, patches were extracted from each biopsy scan. Subsequently, the pre-trained Visual Geometry Group-16 convolutional neural network was used for feature extraction. A representative feature vector was then used as input to an Extreme Gradient Boosting classifier for predicting the binary adverse outcome. We subsequently assessed patient clinical risk using CAPRA score for comparison with the ML pipeline results. The data set included 361 WSIs from 107 patients (56 with adverse pathology at RP). The area under the receiver operating characteristic curves for the ML classification were 0.72 (95% CI, 0.62 to 0.81), 0.65 (95% CI, 0.53 to 0.79) and 0.89 (95% CI, 0.79 to 1.00) for the entire cohort, and GG 2 and GG 3 patients, respectively, similar to the performance of the CAPRA clinical risk assessment. We provide evidence for the potential of ML algorithms to use WSIs of needle core prostate biopsies to estimate clinically relevant prostate cancer outcomes.

Abstract 2222: Detecting clinically significant prostate cancers: Tissue metabolomics refines multiparametric MRI-ultrasound fusion prostate biopsy

Abstract The advent of prostate specific antigen (PSA) testing led to increased early prostate cancer (PCa) detection and has decreased PCa-related death. However, PSA is not cancer-specific, and the challenge persists of differentiating those PCa patients with indolent tumors from those requiring definitive therapy. Metabolomic profiles have the potential to capture molecular dynamics of disease and to reflect disease status before cellular manifestations become observable by histopathology. With clinical, multiparametric magnetic resonance imaging (mpMRI)-positive, fusion biopsy-targeted tissue cores and mpMRI-negative controls in a training-testing cohort design, we studied the potential of magnetic resonance spectroscopy (MRS) to yield cancer metabolomic profiles that could help discriminate likely indolent from clinically significant disease. Using MRS-based PCa metabolomic analyses, performed prior to histology, our approach is able to: determine metabolomic relevations identified in fusion biopsy targets, estimate the scale of PCa metabolomic fields, and detect clinically significant disease in tissues deemed benign or low-risk PCa by pathology and imaging. Our intact tissue MRS metabolomics evaluations indicated significant differences in individual prostate tissue metabolites based on Target-Contralateral (Contral) paired comparisons for both Training and Testing cohorts. We identified metabolomic differences among Target prostate biopsy cores obtained from mpMRI lesions of different PI-RADS scores, and between Target and non-target Contral cores. As a retrospective study, we also analyzed data collected at the time of the initial prostate biopsy alongside patient status across follow up. By introducing metabolomics, as compared with using PSAd or PI-RADS alone, the sensitivity predictions increased by 80.0% and 25.0%, respectively; NPV increased by 18.1% and 8.0%; and accuracy for PSAd increased by 13.0%. PI-RADS accuracy stayed the same Our results show that tissue metabolomic profiles could augment current MR-based imaging findings and histopathological evaluations of fusion biopsies for certain patient populations by more accurately characterizing them into clinically significant or insignificant subgroups. In our analyses, tissue metabolomics alone, or its combination with other clinical parameters, improved sensitivity and negative predictive values, as well as overall accuracy, for our testing cohort. This method, which relies on performing tissue MRS of needle biopsy cores prior to histopathologic analysis, causes no interruption to patient care. Findings from our study demonstrate the utility and translational potential of cancer metabolomics in personalized treatment for PCa and encourages the development of in vivo PCa metabolomic imaging to enhance the diagnostic utility of mpMRI. Citation Format: Leo L. Cheng, Adam S. Feldman, Lindsey A. Vandergrift, Isabella H. Muti, Florian Rumpf, Andrew Gusev, Yannick Berker, Marcella R. Cardoso, Taylor L. Fuss, Emily D. Negroponte, Shulin Wu, Felix Ehret, Christopher A. Dietz, Sarah S. Dinges, Thitinan Chulroek, Edouard Nicaise, Piet Habbel, Martin Ayree, Johannes Nowak, Douglas M. Dahl, Chin-Lee Wu, Mukesh Harisinghani. Detecting clinically significant prostate cancers: Tissue metabolomics refines multiparametric MRI-ultrasound fusion prostate biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2222.

Concordance of MRI-Guided Fusion and Systematic 12-Core Prostate Biopsy for the Detection of Prostate Cancer.

BackgroundMRI-guided fusion biopsy is increasingly utilized over systematic 12-core biopsy for men with MRI-visible prostate lesions.Patients and MethodsPatients with MRI visible lesions who underwent MRI-guided fusion and systematic 12-core biopsy from 2016-2020 in the Intermountain Healthcare (IHC) system were consecutively analyzed. This was in the setting of a continuous quality assurance initiative among the reading radiologists. Primary outcome was prostate cancer (PCa) detection defined by Gleason grade group (GGG) 1 or higher. Clinically significant cancer (CSC) was defined as GGG 2 or higher. Patients were stratified by biopsy date, 2016-2017 and 2018-2021, and lesions were stratified by PI-RADS v2 category.ResultsA total of 184 patients with 324 MRI-detectable lesions underwent both biopsy modalities in the IHC system from 2016 to 2021. CSC was detected in 23.5% of MRI-guided fusion biopsies. Comparing PI-RAD v2 categories 1-3 to categories 4-5, rate of CSC was 10% and 42% respectively. MRI-guided fusion and systematic 12-core biopsies were concordant for PCa in 77% of men and CSC in 83%. MRI-guided fusion biopsy detected PCa in 26/103 and CSC in 20/131 men in whom systematic 12-core biopsy was negative. Systematic 12-core biopsy detected PCa in 17/94 and CSC in 11/122 men in whom MRI-guided fusion was negative.ConclusionsOmitting MRI-guided fusion or systematic 12-core biopsy would have resulted in underdiagnosis of CSC in 11% or 6% of patients respectively. Combining biopsies increased detection rate of CSC. This was in the setting of a continuous quality assurance program at a large community-based hospital.