Prior Negative Prostate Biopsy Research Articles

Incidental prostate cancer after holmium laser enucleation of the prostate: Critical analysis of independent risk factors and impact on surgical outcomes.

The objectives of this study are to evaluate the impact of incidental prostate cancer (iPCa) and its different grade group (GG) on the surgical outcomes of holmium laser enucleation of the prostate (HoLEP) and, furthermore, to assess the independent risk factors associated with the detection of iPCa. A retrospective chart review was conducted at a single institution for HoLEP cases that were performed between 2017 and 2022. Patients with a preoperative diagnosis of prostate cancer and those without baseline prostate-specific antigen (PSA) levels within 1 year were excluded. Four hundred seventeen patients were divided into three groups: benign prostatic hyperplasia-377; clinically insignificant (GG 1)-29; and clinically significant prostate cancer (GG 2-5)-11. The preoperative parameters analysed included age, body mass index, race/ethnicity, use of 5-alpha-reductase inhibitors, PSA, prostate size, PSA density, and history of negative prostate biopsy. To evaluate the association between clinical and demographic variables, a multivariable-adjusted logistic regression analysis was performed. We also assessed intraoperative and post-operative outcomes among these three groups. A total of 417 patients were analysed; 40 (9.6%) patients had iPCa, of which 29 (72.5%) and 11 (27.5%) were clinically nonsignificant and significant prostate cancer, respectively. Of all the demographic and preoperative variables analysed, hypertension was significantly associated with overall prostate cancer diagnosis (p< 0.05), and no other variable including patient age, preoperative PSA, PSA density, prostate size, or prior prostate biopsy were associated with increased risk of overall prostate cancer or clinically significant prostate cancer diagnosis. Most cases of iPCa were GG1, and 34 (85%) were managed with active surveillance. The rate of iPCa after HoLEP was 9.6%, with most cases being GG 1 (72.5%) and managed through active surveillance. Age, prostate size, baseline PSA, and prior negative prostate biopsies were not associated with increased risk of iPCa.

Utility of serum biomarkers for predicting cancer in patients with previous negative prostate biopsy.

To review the role of serum biomarkers: prostate-specific antigen (PSA), PSA density (PSAD), free:total PSA ratio, prostate health index (PHI) and PHI density (PHID), along with magnetic resonance imaging (MRI) for identification of clinically significant prostate cancer (PCa), comparing their utility in patients with persistently raised PSA levels after a prior negative prostate biopsy (PNB). In this single-centre prospective observational study conducted from September 2015 to October 2020, patients underwent a saturation biopsy via the transperineal route. If a Prostate Imaging Reporting and Data System version 2 (PIRADS) 3 and above lesion was seen on MRI, targeted biopsies were also obtained. Information on clinical history, lesion characteristics, PIRADS classification and follow-up was collected. The sensitivity, specificity and area under curve (AUC) for each of the biomarkers were calculated. 351 men underwent saturation biopsy with or without targeted biopsies. 103 patients had a PNB. Among this PNB cohort, 43 (41.7%) men had a benign outcome, while 60 (58.3%) men had histopathologically diagnosed PCa, of which 41 (39%) were clinically significant. All patients underwent multiparametric MRI scans prior to biopsy. Within this cohort, PHI and PHID had the best abilities to predict for clinically significant PCa with an AUC of 0.73 and 0.70 respectively, compared to 0.65 for PSAD, 0.34 for free:total PSA and 0.56 for PSA. A significant proportion of patients are diagnosed with PCa after a PNB. This study shows that PHI and PHI densities may be suitable adjuncts predicting for clinically significant PCa in patients with PNB.

MP016 - Compаrative study of transperineal MRI/US fusion biopsy and systematic transrectal ultrasound guided biopsy in patients with a history of prior negative prostate biopsy.

MP016 - Compаrative study of transperineal MRI/US fusion biopsy and systematic transrectal ultrasound guided biopsy in patients with a history of prior negative prostate biopsy.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Increasing Utilization of MRI Before Prostate Biopsy in Black and Non-Black Men: An Analysis of the SEER-Medicare Cohort.

OBJECTIVE. The potential for significant disparities exists in the setting of increased adoption of prostate MRI. We sought to assess temporal trends in the utilization of MRI before prostate biopsy in a nationally representative sample. MATERIALS AND METHODS. Using the SEER-Medicare linked database, we identified men undergoing prostate biopsy who had an MRI within 6 months of diagnosis of prostate cancer. Men were stratified according to whether they were biopsy naive or had undergone a prior negative prostate biopsy. RESULTS. We identified 82,483 men undergoing prostate biopsy in SEER-Medicare from 2008 to 2015 of whom 78,253 were biopsy naive and 4230 had a known prior negative biopsy. We found that the percentage of patients who received an MRI before biopsy has increased from 2008 to 2015 in biopsy-naive men (0.5-8.2%; p < .001), men with a prior negative biopsy (1.4-25.5%; p < .001), and overall (0.5-9.2%; p < .001). On multivariable modeling, the odds ratio (OR) of a patient undergoing an MRI before biopsy for Black men (OR, 0.4; 95% CI, 0.3-0.5; p < .001) was half that of White men, and the OR of MRI before biopsy in men from the Northeast (OR, 3.4; 95% CI, 2.8-4.3; p < .001) was more than three times that of men from the West. CONCLUSION. The steady overall increase in the utilization of MRI before prostate biopsy since 2008 has been associated with significant racial and regional disparities in utilization.

Analysis of risk factors for determining the need for prostate biopsy in patients with negative MRI

To analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn’t need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.

Assessment of magnetic resonance imaging (MRI)-fusion prostate biopsy with concurrent standard systematic ultrasound-guided biopsy among men requiring repeat biopsy.

The role of magnetic resonance imaging (MRI)-fusion biopsy (FB) remains unclear in men with prior negative prostate biopsies. This study aimed to compare the diagnostic accuracy of FB with concurrent systematic biopsy (SB) in patients requiring repeat prostate biopsies. Patients with previous negative prostate biopsies requiring repeat biopsies were included. Those without suspicious lesions (≥Prostate Imaging-Reporting and Data System [PI-RADS] 3) on MRI were excluded. All patients underwent FB followed by SB. The primary outcome was the sensitivity for clinically significant prostate cancer (Gleason score ≥7). The secondary objective was identification of potential predictive factors of biopsy performance. A total of 53 patients were included; 41 (77%) patients were found to have clinically significant prostate cancer. FB had a higher detection rate of significant cancer compared to SB (85% vs. 76%, respectively, p=0.20) and lower diagnosis of indolent (Gleason score 3+3=6) cancer (10% vs. 27%, respectively, p=0.05). FB alone missed six (15%) clinically significant cancers, compared to 10 (24%) with SB. SB performance was significantly impaired in patients with anterior lesions and high prostate volumes (p<0.05). There was high degree of pathological discordance between the two approaches, with concordance seen in only 34% of patients. In patients with prior negative biopsies and ongoing suspicion for prostate cancer, a combined approach of FB with SB is needed for optimal detection and risk classification of clinically significant disease. Anterior tumors and large prostates were significant predictors of poor SB performance and an MRI-fusion alone approach in these settings could be considered.

Prostate-Specific Antigen Modulatory Effect of a Fermented Soy Supplement for Patients with an Elevated Risk of Prostate Cancer: a Non-Randomized, Retrospective Observational Registration

Objective: To investigate the efficacy of a 6-month fermented soy supplement (equol-containing), measured by prostate-specific antigen (PSA) stabilization or PSA decrease from baseline (PSA modulatory effect) in men with an elevated risk of prostate cancer (PCa), with a WHO performance 0-2 and a follow-up of 12 months. Methods: The patient population consisted of men with an elevated risk of PCa and a prior negative prostate biopsy within 1 year from starting therapy. Serum PSA values were recorded at inclusion (iPSA), at 6 months (1PSA), and optionally at 12 months (2PSA). Statistical analysis was carried out using the Wilcoxon rank sum test (p < 0.05). Results: In total, 137 men used fermented soy for any prostatic reason. After inclusion criteria for an elevated risk of PCa and a prior negative prostate biopsy, we selected 58 patients. Among these, there was a significant PSA modulatory effect (iPSA-1PSA, p = 0.003). This modulatory effect was more strongly evident in the subgroup of patients with an elevated iPSA (≥ 4 ng/ml) (n = 33, iPSA-1PSA, p = 0.003, iPSA-2PSA, p = 0.002). Conclusions: We demonstrated a significant PSA modulatory effect of a 6-month fermented soy supplement in men with an elevated risk of PCa and a prior negative prostate biopsy. This positive effect is currently being investigated in a prospective study. Further evaluation of the role of fermented soy supplements is warranted in a preventive and therapeutic setting of men at an elevated risk of PCa.

A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy

BackgroundInitial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate (IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.MethodsAs part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2–10 ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.Results229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35 and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.ConclusionsThe EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2–10 ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.

68Ga-PSMA-11 PET/mpMRI for local detection of primary prostate cancer in men with a negative prior biopsy

Multiparametric MRI (mpMRI) represents the current gold standard for the detection of primary prostate cancer (PC) after a negative biopsy. PSMA PET imaging has been introduced in the diagnostic work-up of PC with high accuracy, but is currently mainly utilised in the setting of biochemical recurrence. This study aimed to determine the efficacy of combined 68Ga-PSMA-11 PET/mpMRI imaging to detect PC in patients with previously negative prostate biopsies. A total of 57 patients who had undergone at least one prior negative prostate biopsy were included in this retrospective analysis. All patients underwent 68Ga-PSMA-11 PET/mpMRI imaging of the prostate. mpMRI was evaluated according to the PIRADS classification system and 68Ga-PSMA-11 PET was rated on a 5-point Likert scale (1: PC highly unlikely; 2: PC unlikely; 3: presence of PC is equivocal; 4: PC likely; 5: PC highly likely). All patients received a systematic random biopsy as well as a targeted transrectal biopsy of lesions suspicious on imaging. Imaging and histological biopsy outcomes were compared on a per-patient basis. In the histological analysis, 35/57 (61.4 %) patients harboured PC lesions. In patients with biopsy-proven PC, 21/35 (60.0 %) had a PI-RADS 4 or 5 lesion on mpMRI and 28 /35 (80.0 %) had a PET rating of 4 or 5. Combined 68Ga-PSMA-11 PET/mpMRI missed only one patient with a Gleason score (GS) 7a tumour (rating of 1 or 2 in both PET and mpMRI). Limitations include the retrospective analysis as well as possible false negative biopsy results even in a fusion biopsy setting. In this initial analysis, the combined 68Ga-PSMA-11 PET/mpMRI proved to be a valuable imaging tool to guide prostate biopsies for the detection of PC in patients with a negative prior biopsy. In this approach, 68Ga-PSMA-11 PET and mpMRI show partially complementary findings that enhance the detection of PC lesions.

Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt

HintergrundMänner in Deutschland sterben früher als Frauen und nehmen weniger häufig Krebsvorsorgeuntersuchungen wahr.FragestellungZiel war die prospektive Evaluation einer „Movember-Gesundheitsinitiative“ am Universitätsklinikum Frankfurt (UKF) im November 2019.MethodenIm Rahmen der „Movember-Gesundheitsinitiative“ wurde allen männlichen Mitarbeitern des UKF ab dem 45. Lebensjahr und bei erstgradiger familiärer Vorbelastung eines Prostatakarzinoms ab dem 40. Lebensjahr im November 2019 gemäß S3-Leitlinien der Deutschen Gesellschaft für Urologie (DGU) eine Prostatakarzinom-Vorsorgeuntersuchung angeboten.ErgebnisseInsgesamt nahmen 14,4 % der Mitarbeiter teil. Eine familiäre Vorbelastung gaben insgesamt 14,0 % Teilnehmer an. Das mediane Alter betrug 54 Jahre. Der mediane PSA(prostataspezifisches Antigen)-Wert lag bei 0,9 ng/ml, der mediane PSA-Quotient bei 30 %. Bei 5 % (n = 6) zeigte sich ein suspekter Tastbefund in der DRU (digital-rektale Untersuchung). Nach Altersstratifizierung (≤ 50 vs. > 50 Lebensjahre) zeigten sich signifikante Unterschiede im medianen PSA-Wert (0,7 ng/ml vs. 1,0 ng/ml, p < 0,01) und der bereits zuvor durchgeführten urologischen Vorsorge (12,1 vs. 42,0 %, p < 0,01). Vier Teilnehmer (3,3 %) zeigten erhöhte Gesamt-PSA-Werte. Bei 32,2 % der Teilnehmer zeigte sich mindestens ein kontrollbedürftiger Befund. Insgesamt wurden 6 Prostatabiopsien durchgeführt. Hierbei zeigte sich in einem Fall ein intermediate-risk Prostatakarzinom (Gleason 3 + 4, pT3a, pPn1, pNx, R0).SchlussfolgerungungIm Rahmen der UKF-Movember-Gesundheitsinitiative 2019 konnten durch ein Vorsorgeangebot 121 Männer für eine Prostatakrebs-Vorsorge inklusive PSA-Testung gewonnen werden. Auffällige/kontrollbedürftige Befunde zeigten sich bei 32,2 %. Bei einem Mitarbeiter wurde ein therapiebedürftiges Prostatakarzinom entdeckt und therapiert.

Clinical analysis of the extracellular vesicle-fingerprint score blood test to refine the prediction of clinically significant prostate cancer and avoid prostate biopsy.

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]

MP13-15 68GA-PSMA-11 PET/MPMRI FOR DETECTION OF PRIMARY PROSTATE CANCER IN PREVIOUSLY NEGATIVE-BIOPSIED MEN

INTRODUCTION AND OBJECTIVE: Multiparametric MRI (mpMRI) represents the current gold standard for detection of primary prostate cancer (PCa) after negative biopsy. PSMA PET imaging has been introduced in the diagnostic work-up of PCa with high specificity, currently mainly utilized in biochemical recurrence. Therefore, the aim of this investigation was to determine the efficacy of combined 68Ga-PSMA-11 PET/mpMRI imaging to detect PCa in patients with previously negative prostate biopsy. METHODS: 57 patients (pts.) who underwent at least one prior negative prostate biopsy were included in this analysis. All pts. underwent 68Ga-PSMA-11 PET/mpMRI imaging of the prostate. Lesions on mpMRI were evaluated according to the PI-RADS classification system and lesions on 68Ga-PSMA-11 PET were rated according to a 5-point scale on a sextant basis (1: PCa highly unlikely; 2: PCa unlikely; 3: presence of PCa is equivocal; 4: PCa likely; 5: PCa highly likely). All pts. received a systematic random biopsy as well as a targeted transrectal biopsy of lesions suspicious on imaging. Results of imaging and histological analysis of prostate biopsies were compared per patient and per prostate sextant. RESULTS: On histological analysis 35/57 (61.4%) of pts. and 75/342 (21.9%) of sextants showed PCa lesions. In patients with biopsy confirmed PCa 21/35 (60.0%) showed a PI-RADS 4 or 5 lesion on mpMRI and 28/35 (80.0%) presented with a PET rating of 4 or 5. 20/75 (26.7%) of sextants with histological confirmed PCa showed a PI-RADS 4 or 5 lesion on mpMRI and 26/75 (34.7%) of sextants presented with a PET rating of 4 or 5. Combined 68Ga-PSMA-11 PET/mpMRI missed only one patient with a Gleason-Score (GS) 7a tumor (rating of 1 or 2 in both, PET and mpMRI). Limitations represent the retrospective analysis as well as possible false negative biopsy results even in a fusion biopsy setting. CONCLUSIONS: In this initial analysis, 68Ga-PSMA-11 PET/mpMRI proved to be a valuable imaging tool to guide prostate biopsies for detection of PCa in patients after prior negative biopsy. Hereby, 68Ga-PSMA-11 PET and mpMRI show complementary findings thus increasing detection of PCa lesions. Source of Funding: none

Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools

BackgroundOnline clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool.MethodsWe created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance.ResultsHigh-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004).ConclusionsWe have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.

MRI ultrasound fusion biopsy in prostate cancer detection: Are randomized clinical trials reproducible in everyday clinical practice?

The aim of this study was to evaluate the performance of multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-targeted biopsies (TB) in men with primary and repeated biopsies comparing the cancer detection rate (CDR) of random biopsies (RB) + TB versus only TB. The present study is a real-life study on patients with primary and prior negative prostate biopsies with suspicious PCa. A total of 130 men with prostate-specific antigen (PSA) value >2.5 ng/dL and/or abnormal digital rectal examination (DRE) were included in the study and subjected to mpMRI. Patients with >2 previous biopsies and/or with ⩾3 suspected lesions on MRI and/or prostate imaging-reporting and data system (PIRADS) value ⩾4 (n:30 pts) were subjected only to TB on the areas indicated by mpMRI. All the other patients (n:70 pts) were subjected to standard random laterally directed 10-core plus TB on the areas indicated by mpMRI. The overall CDR was 53% (53/100). In relation to PIRADS score, the overall CDR was 0, 40% (12/30), 56.83% (29/51), and 84% (11/13) for PIRADS 2, 3, 4, and 5, respectively. According to biopsy modality, CDR for RB + TB was 50% (35/70) and CDR for TB was 60% (18/30) with a p-value of 0.3632. MRI-US fusion biopsy is associated with a high CDR of clinically significant PCa (csPCa). MRI-US fusion biopsy could be a reasonable approach in patients with previous negative biopsy and high PIRADS score on MRI, to ensure a high CDR of csPCa and to reduce the diagnosis of clinically insignificant tumors.

Value of MR-US fusion in guidance of repeated prostate biopsy in men with PSA < 10 ng/mL

PurposeWe want to investigate whether MR-US fusion can improve the detection rates of clinically significant prostate cancer in patients with prior negative prostate biopsy with PSA level <10 ng/mL. MethodsThirty nine patients who had previous a history of negative prostate biopsy and PSA levels <10 ng/mL were included in this study. MR was performed before the biopsy and graded using PIRADS V2. We labeled patients with index lesions with PIRADS scores of 3 or above as the MR-positive group, while patients with PIRADS scores of 1 or 2 were the MR-negative group. Two cores of added biopsy (AB) were performed per each index lesion under MR-US fusion. Twelve cores randomized systematic biopsy (SB) were followed. In MR negative group, two cores of AB were obtained in transition zone, followed by SB. Overall cancer and clinically significant cancer detection rates by patients and by cores were analyzed, and compared between MR-positive and negative group. ResultsThe overall cancer detection rates were 51.3% by patient based and 13.8% by core based. While all of AB positive cancer patients were clinically significant cancer patients, five out of seven (71.4%) AB negative cancer patients were clinically insignificant cancer patients. AB results turned another four cancer patients from insignificant to significant cancer. The cancer detection rates between MR-positive and negative group were statistically significant. ConclusionsAdditional biopsy using MR–US fusion showed improved detection of clinically significant prostate cancer.

Developing a Chinese PI-RADS v2-based nomogram for predicting clinically significant prostate cancer in patients with a prior negative biopsy

Objective: To develop a nomogram based on prostate imaging reporting and data system version 2 (PI-RADS v2) to predict clinically significant prostate cancer in patients with a prior negative prostate biopsy. Methods: The clinical and pathological data of 231 patients who underwent repeat prostate biopsy and multiparametric MRI (mpMRI) were reviewed. Based on PI-RADS v2, the mpMRI results were assigned as PI-RADS grade from 0 to 2. A Logistic regression nomogram for predicting the probabilities of clinically significant prostate cancer were constructed. The performances of the nomogram were assessed using area under the receiver operating characteristic (ROC) curve, calibrations and decision curve analysis. Results: Of the total 231 repeat prostate biopsy patients, clinically significant prostate cancer was detected in 59 cases(25.5%). In multivariate Logistic regression analysis, age, prostate specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) and mpMRI results were significant independent predictors of the diagnosis of clinically significant prostate cancer (P<0.05). The nomogram with super predictive accuracy were constructed (AUC=0.927, P<0.001), and exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of threshold probabilities . Conclusions: PI-RADS v2 combined with age, PSA, PV and DRE can predict the probability of clinically significant prostate cancer in patients with negative initial biopsies. The nomogram generated may help the decision-making process in patients with prior benign histology before the performance of repeat biopsy.

Fusion prostate biopsy outperforms 12-core systematic prostate biopsy in patients with prior negative systematic biopsy: A multi-institutional analysis

Introduction and objectivesPatients with persistently elevated prostate specific antigen (PSA) and prior negative 12-core TRUS prostate biopsy (or biopsies) (systematic biopsy—SBx) are a diagnostic challenge. Repeat SBx or saturation biopsy in this cohort has been shown to have an even lower yield. The aim of our study is to compare the prostate cancer yield of magnetic resonance imaging (MRI) fusion biopsy (FBx) to SBx in a multi-institutional cohort comprised of patients with prior negative biopsies. MethodsA multi-institutional review was performed on patients with a history of one or more prior negative SBx who underwent multiparametric MRI (mpMRI), followed by FBx and SBx in the same session. Imaging protocol was standardized across institutions and institutional genitourinary radiologists and pathologists reviewed mpMRI and pathology, respectively. Gleason score (GS) distribution and risk classifications were recorded. Prostate cancer with GS ≥3 + 4 was defined as clinically significant (CS). Univariate and multivariable logistic regression was done to identify predictors of cancer detection on SBx and FBx. ResultsSeven-hundred seventy-nine patients from four institutions were included in the study. Median age and prostate specific antigen (IQR) were 63.1 (58.5–68.0) years and 8.5 (5.9–13.1)ng/dl, respectively. Median number of prior negative biopsies (range) was 2.0 (1–16). The cancer detection rate (CDR) in the cohort was 346/779 patients (44.4%). Total CS CDR was 30.7% (239/779 patients), with FBx detecting 26.3% (205/779) of patients with CS disease and SBx diagnosing an additional 4.4% (34/779) of patients (P<0.001). Furthermore, of all cancers detected by each modality, FBx detected a higher proportion of CS cancer compared to SBx (one negative biopsy: 75 vs. 50%, P<0.001, 2–3 negative biopsy: 76 vs. 61%, P = 0.006, 4 or more negative biopsies: 84 vs. 52%, P = 0.006). As such, SBx added a relatively small diagnostic value to FBx for detecting CS disease (one negative biopsy 3.5%, 2–3 negative biopsies 5%, 4 or more negative biopsies: 1%). FBx also outperformed SBx for upgrading patients to an intermediate or high-risk cancer category (GS>6) (one negative biopsy 11.5% vs. 3.6%, 2–3 negative biopsy 10.3% vs. 5.3%, 4 or more negative biopsies 19.1% vs. 1.1%). On multivariable analysis, the number of prior negative biopsies was a significant negative predictor of CS CDR on SBx (P = 0.006), but not on FBx (P = 0.151). ConclusionsUsing a large multi-institutional cohort, we were able to demonstrate that FBx outperformed SBx in patients with prior negative systematic biopsy. This was due, in part, to the decreasing CS CDR by SBx with increased number of prior biopsies. The yield of FBx stayed constant and did not decrease with increased number of prior negative biopsies. Therefore, repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients.

Initial series of magnetic resonance imaging (MRI)-fusion targeted prostate biopsy using the first transperineal targeted platform available in the USA.

To describe a step-by-step guide for using the first transperineal targeted prostate biopsy platform available in the USA. A total of 32 men with elevated prostate-specific antigen (PSA) levels were diagnosed with a region of interest on multiparametric magnetic resonance imaging (mpMRI) between February 2017 and January 2018. The transperineal targeted prostate biopsy procedure was accomplished via a transperineal approach and used a stepper, combined with advanced mpMRI/transrectal ultrasound fusion software, to perform targeted prostate biopsy. The detection of overall and clinically significant prostate cancer (PCa) was assessed as well as the rate of complications. The median patient age was 68.0years and the median PSA was 8.0ng/mL. Two patients (6%) were active surveillance candidates and 16 (50%) had a prior negative prostate biopsy. The detection rates for overall and clinically significant PCa were 81% and 59%, respectively. The two candidates for active surveillance and eight of the patients with a prior negative prostate biopsy had clinically significant PCa confirmed on targeted biopsy. There were no peri-operative complications. These results demonstrate the promising potential of the first transperineal targeted prostate biopsy platform in the USA as an alternative diagnostic method for PCa.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). The study included 74 men with a median age of 65years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. 4.