Negative Prostate Biopsy Research Articles

Systematic biopsy should not be omitted in the era of combined magnetic resonance imaging/ultrasound fusion-guided biopsies of the prostate

To evaluate prostate cancer detection rates with classical trans-rectal ultrasound-guided systematic 10-core biopsies (SB), targeted biopsies (TB) guided by magnetic resonance (MR)/US fusion imaging and their combination in biopsy-naïve and patients with previously negative prostate biopsies. We compared pathology results after radical prostatectomy with biopsy findings. Consecutive patients with prostate imaging-reporting and data system lesions grade ≥ 3 submitted to MRI/US-guided TB and subsequent standard 10-core SB between December 2015 and June 2019 were analyzed. Detection rate (TB- or SB-positive) in 563 included patients (192 naïve, 371 with previous biopsies) was 56.7% (67.7% for the first, 50.9% for repeated biopsies). With TB (disregarding SB), the rates were 41.4%, 52.1% and 35.8%, respectively. With SB (disregarding TB), the rates were 49.1%, 63.0% and 41.8%, respectively. Eventually, 118 patients underwent surgery and clinically significant cancer was found in 111 (94.1%) specimens. Of those, 23 (20.7%) would have been missed had we relied upon a negative TB and 14 (12.6%) would have been missed had we relied upon a negative SB, disregarding a positive finding on the alternative biopsy template. SB should not be omitted since TB and SB combination have higher detection rate of clinically relevant prostate cancer than either procedure alone.

PD17-10 THE SIGNIFICANCE OF MULTIPLE NEGATIVE BIOPSIES IN PATIENTS ON ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (PD17)1 Sep 2021PD17-10 THE SIGNIFICANCE OF MULTIPLE NEGATIVE BIOPSIES IN PATIENTS ON ACTIVE SURVEILLANCE Nabila Khondakar, Jillian Egan, Luke O'Connor, Michael Ahdoot, Cheyenne Williams, Michael Daneshvar, Nitin Yerram, Jeunice Owens-Walton, Patrick Gomella, Sandeep Gurram, Peter Choyke, Maria Merino, Bradford Wood, Baris Turkbey, and Peter Pinto Nabila KhondakarNabila Khondakar More articles by this author , Jillian EganJillian Egan More articles by this author , Luke O'ConnorLuke O'Connor More articles by this author , Michael AhdootMichael Ahdoot More articles by this author , Cheyenne WilliamsCheyenne Williams More articles by this author , Michael DaneshvarMichael Daneshvar More articles by this author , Nitin YerramNitin Yerram More articles by this author , Jeunice Owens-WaltonJeunice Owens-Walton More articles by this author , Patrick GomellaPatrick Gomella More articles by this author , Sandeep GurramSandeep Gurram More articles by this author , Peter ChoykePeter Choyke More articles by this author , Maria MerinoMaria Merino More articles by this author , Bradford WoodBradford Wood More articles by this author , Baris TurkbeyBaris Turkbey More articles by this author , and Peter PintoPeter Pinto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001999.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low-risk prostate cancer patients receive multiple biopsies over the course of active surveillance (AS). MRI enables earlier detection of disease and may help to risk-stratify patients. We aimed to assess the significance of multiple negative biopsies in AS patients who received MRI per our AS protocol. We also compared disease progression in patients who had multiple combined MRI-targeted and 12-core systematic biopsies (combined biopsy), versus multiple systematic biopsies alone. METHODS: We queried our database of patients referred for possible AS between 2007 and 2020, and who had confirmatory biopsy. Patients with at least three total biopsies (diagnostic, confirmatory, and follow-up) and Gleason Grade ≤2 on confirmatory biopsy were included. Negative biopsy was defined as no cancer on any biopsy cores. Kaplan-Meier survival analysis was used to assess time to progression. Analyses were repeated in subgroups who received combined vs. systematic biopsy. RESULTS: A total of 219 patients met inclusion criteria. Median age at confirmatory biopsy was 62 years. Distribution of biopsy results was as follows: 107 patients (48.9%) had zero negative biopsies, 49 (22.3%) had consecutive negative biopsies, 51 (23.3%) had only one negative biopsy, and 11 (5.0%) had non-consecutive negative biopsies. Having multiple negative biopsies was associated with longer progression free survival (PFS) (log-rank p<0.0001). When stratified by biopsy type, multiple negative combined biopsies were associated with longer PFS (p<0.0001) whereas multiple negative systematic biopsies were not (p=0.34). Median time to progression was 3.1 years with zero negative biopsies, 6.5 years with one negative biopsy, 7.7 years with consecutive negative biopsies, and 8.3 years with non-consecutive negative biopsies. CONCLUSIONS: In an AS cohort of patients with GG ≤2 at time of confirmatory biopsy, having at least one negative biopsy was associated with PFS time more than double that of patients with no negative biopsies. Our findings suggest that patients with multiple negative prostate biopsies do not require frequent surveillance biopsies that traditionally have been offered to AS patients. Source of Funding: NIH Intramural Funding, NIH Medical Research Scholars Program, Foundation for the NIH © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e288-e288 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nabila Khondakar More articles by this author Jillian Egan More articles by this author Luke O'Connor More articles by this author Michael Ahdoot More articles by this author Cheyenne Williams More articles by this author Michael Daneshvar More articles by this author Nitin Yerram More articles by this author Jeunice Owens-Walton More articles by this author Patrick Gomella More articles by this author Sandeep Gurram More articles by this author Peter Choyke More articles by this author Maria Merino More articles by this author Bradford Wood More articles by this author Baris Turkbey More articles by this author Peter Pinto More articles by this author Expand All Advertisement Loading ...

Initial Prostate Health Index (phi) and phi density predicts future risk of clinically significant prostate cancer in men with initial negative prostate biopsy: a 6-year follow-up study.

Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. This study aims to investigate the role of initial phi and phi density in predicting future PCa risk in men with initial negative biopsy. Five hundred sixty nine men with PSA 4-10 ng/mL were recruited between 2008 and 2015 for prostate biopsy with prior phi. Electronic clinical record of men with initial negative biopsy was reviewed. Patients and follow-up doctors were blinded to phi. Kaplan-Meier curves were used to analyze the PCa-free survival in different baseline phi and phi density groups. Four hundred sixty-one men with complete follow-up data were included. Median follow-up is 77 months. PCa and HGPCa was diagnosed in 8.2% (38/461) and 4.8% (22/461) of cohort respectively. A higher baseline phi value was associated with PCa (p = 0.003) and HGPCa (p < 0.001). HGPCa was diagnosed in 0.6% (1/163) of phi < 25, 4.6% (9/195) of phi 25-34.9, and 11.7% (12/103) of phi ≥ 35 (p < 0.001). HGPCa was diagnosed in 0% (0/109) and 21.0% (13/62) with phi density of <0.4 and ≥1.2, respectively, (p < 0.001). Kaplan-Meier curves showed phi and phi density predicted PCa and HGPCa diagnoses (log-rank test, all p ≤ 0.002). Initial phi or phi density predicted 6-year risk of PCa in men with initial negative prostate biopsy. Men with higher phi (≥35) or phi density (≥1.2) need closer follow-up and repeated investigation, while men with lower phi (<25) or phi density (<0.4) could have less frequent follow-up.

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.

Development and validation of a predictive model for determining clinically significant prostate cancer in men with negative magnetic resonance imaging after transrectal ultrasound-guided prostate biopsy.

The interpretation of negative magnetic resonance imaging (MRI) screening results for clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade ≥group 2) is debatable and poses a clinical dilemma for urologists. No nomograms have been developed to predict csPCa in such populations. In this study, we aimed to develop and validate a model for predicting the probability of csPCa in men with negative MRI (PI-RADS score 1-2) results after transrectal ultrasound-guided systematic prostate biopsy. The development cohort consisted of 728 patients with negative MRI results who underwent subsequent prostate biopsy at our center between January 1, 2014 and December 31, 2017. The patients' clinicopathologic data were recorded. The Lasso regression was used for data dimension reduction and feature selection, then multivariable binary logistic regression was used to build a predictive model with regression coefficients. The model was validated in an independent cohort of 334 consecutive patients from January 1, 2018 and June 30, 2020. The performance of the predictive model was assessed with respect to discrimination, calibration, and decision curve analysis. The predictors incorporated in this model included age, history of previous negative prostate biopsy, prostate specific antigen density (PSAD), and lower urinary tract symptoms, with PSAD being the strongest predictor. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.816-0.933) and good calibration (unreliability test, p = .540). Decision curve analysis demonstrated that the model was clinically useful. This study presents a good nomogram that can aid pre-biopsy risk stratification for the detection of csPCa, and that may help inform biopsy decisions in patients with negative MRI results.

Integrative Machine Learning Prediction of Prostate Biopsy Results From Negative Multiparametric MRI.

Multiparametric MRI (mpMRI) is commonly recommended as a triage test prior to any prostate biopsy. However, there exists limited consensus on which patients with a negative prostate mpMRI could avoid prostate biopsy. To identify which patient could safely avoid prostate biopsy when the prostate mpMRI is negative, via a radiomics-based machine learning approach. Retrospective. Three hundred thirty patients with negative prostate 3T mpMRI between January 2016 and December 2018 were included. A 3.0 T/T2-weighted turbo spin echo (TSE) imaging (T2 WI) and diffusion-weighted imaging (DWI). The integrative machine learning (iML) model was trained to predict negative prostate biopsy results, utilizing both radiomics and clinical features. The final study cohort comprised 330 consecutive patients with negative mpMRI (PI-RADS < 3) who underwent systematic transrectal ultrasound-guided (TRUS) or MR-ultrasound fusion (MRUS) biopsy within 6 months. A secondary analysis of biopsy naïve subcohort (n=227) was also conducted. The Mann-Whitney U test and Chi-Squared test were utilized to evaluate the significance of difference of clinical features between prostate biopsy positive and negative groups. The model performance was validated using leave-one-out cross-validation (LOOCV) and measured by AUC, sensitivity, specificity, and negative predictive value (NPV). Overall, 306/330 (NPV 92.7%) of the final study cohort patients had negative biopsies, and 207/227 (NPV 91.2%) of the biopsy naïve subcohort patients had negative biopsies. Our iML model achieved NPVs of 98.3% and 98.0% for the study cohort and subcohort, respectively, superior to prostate-specific antigen density (PSAD)-based risk assessment with NPVs of 94.9% and 93.9%, respectively. The proposed iML model achieved high performance in predicting negative prostate biopsy results for patients with negative mpMRI. With improved NPVs, the proposed model can be used to stratify patients who in whom we might obviate biopsies, thus reducing the number of unnecessary biopsies. 3 TECHNICAL EFFICACY: Stage 2.

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.

Risk stratification in men with a negative prostate biopsy: an interim analysis of a prospective cohort study.

To investigate whether a risk score for prostate cancer (PCa) lifetime risk can be used to optimise triaging of patients with a negative prostate biopsy, but under sustained suspicion of PCa. In this prospective clinical study, we included, and risk scored patients who had a PCa-negative transrectal ultrasonography (TRUS)-guided prostate biopsy, but elevated prostate-specific antigen (PSA), a suspicious prostate digital rectal examination and/or a positive family history (FH) of PCa. The risk score estimated individual lifetime risk of PCa, based on a polygenic risk score (33 single nucleotide polymorphisms), age, and FH of PCa. Patients were followed, under urological supervision, for up to 4years with annual controls, always including PSA measurements. Multiparametric magnetic resonance imaging (mpMRI) and/or prostate biopsy was performed at selected annual controls depending on risk score and at the urologist's/patient's discretion, which means that the follow-up differed based on the risk score. We included 429 patients. After risk scoring, 376/429 (88%) patients were allocated to a normal-risk group (<30% PCa lifetime risk) and 53/429 (12%) to a high-risk group (≥30% PCa lifetime risk). The high-risk group had significantly different follow-up, with more biopsy and mpMRI sessions compared to the normal-risk group. PCa was detected in 89/429 (21%) patients, with 67/376 (18%) patients diagnosed in the normal-risk group and 22/53 (42%) in the high-risk group. There was no statistically significant difference in the cumulative incidence of PCa between the normal-risk group and the high-risk group after 4years of follow-up. Currently, 67/429 (16%) patients are still being followed in this ongoing study. In a 4-year perspective, our PCa lifetime risk score did not demonstrate significant prognostic value for triaging patients, with a negative TRUS-guided biopsy and sustained suspicion of PCa.

The current value of histological findings in negative prostate biopsies to predict the future risk of clinically significant prostate cancer

BackgroundRepeat prostate biopsy (PBx) is recommended under persistent suspicion of prostate cancer (PCa) or in the face of the following findings: atypical small acinar proliferation (ASAP); extense (≥3 biopsy sites) high-grade prostatic intraepithelial neoplasia (HGPIN); or HGPIN with atypical glands; suspicious for adenocarcinoma (PIN-ATYP). Nowadays; multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted PBx (MRI-TBx) are recommended in repeat PBx. Our objective was to analyze the current value of ASAP; mHGPIN; PIN-ATYP and other histological findings to predict clinically significant PCa (csPCa) risk. MethodsRetrospective analysis of 377 repeat PBxs. MRI-TBx was performed when Prostate Imaging-Reporting and Data System (PI-RADS) score >3 and 12-core transrectal ultrasound (TRUS) systematic PBx when ≤2. ASAP; HGPIN; mHGPIN; PIN-ATYP; and 8 other histological findings were prospectively reported in negative PBx. CsPCa was defined as ISUP group grade >2. ResultsIncidence of ASAP; multifocal HGPIN (mHGPIN) and PINATYP was 4.2%; 39.7% and 3.7% respectively; and csPCa rate was statistically similar among men with these histological findings. However; the rate of csPCa was 22.2% when proliferative inflammatory atrophy (PIA) was present; and 36.1% when it was not. PIA was the only histological finding which predicted lower risk of csPCa; with an OR of 0.54 (95%CI: 0.308−0.945; P = .031). In addition; PIA was an independent predictor of a model combining clinical variables and mpMRI which reached area under de ROC curve of 0.86 (95%CI: 0.83−0.90). ConclusionPIA emerged as the only predictive histological finding of csPCa risk and can contribute to a predictive model. mHGPIN failed to predict csPCa risk. The low incidence of ASAP (4.2%) and PIN-ATYP (3.7%) prevented us from drawing conclusions.

Prostate-specific antigen density during dutasteride treatment for 1year predicts the presence of prostate cancer in benign prostatic hyperplasia after the first negative biopsy (PREDICT study).

To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy. Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5mg dutasteride daily for 1year. They underwent a repeat prostate biopsy after 1year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group. Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1year was significantly different (P=0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P=0.102), prostate-specific antigen levels at 6, 9 and 12months were significantly different (P=0.002, P=0.001 and P<0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1year was significantly different (-4.25±76.5% vs -38.0±28.7%, P=0.001). Using a multivariate analysis, a >10% increase of prostate-specific antigen density at 1year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P<0.001). In the present study cohort, >10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy.

Serum Metabolic Profiling Identifies a Biomarker Panel for Improvement of Prostate Cancer Diagnosis.

ObjectivesTo identify and validate a biomarker panel by serum metabolic profiling for improvement of PCa diagnosis.Materials and MethodsTotally, 134 individuals were included in this study. Among them, 39 PCa patients and 45 control patients (negative prostate biopsy) were involved in the discovery phase and 50 healthy controls were enrolled for validation phase of metabolomics study. LC-MS Analysis was used for the identification of the serum metabolites of patients.ResultsLogistics regression analysis shows that 5 metabolites [dMePE(18:0/18:2), PC(16:0/20:2), PS(15:0/18:2), SM(d16:0/24:1], Carnitine C14:0) were significantly changed in PCa patients compared with control patients. A metabolic panel (MET) was calculated, showing a significantly higher diagnostic performance than PSA in differentiating PCa from control patients [AUC (MET vs. PSA): 0.823 ± 0.046 vs. 0.712 ± 0.057, p<0.001]. Moreover, this panel was superior to PSA in distinguishing PCa from negative prostate biopsies when PSA levels were less than 20 ng/ml [AUC (MET vs. PSA]: 0.836 ± 0.050 vs. 0.656 ± 0.067, p<0.001]. In the validation set, the MET panel yielded an AUC of 0.823 in distinguishing PCa patients from healthy controls, showing a significant improvement of PCa detection.ConclusionsThe metabolite biomarker panel discovered in this study presents a good diagnostic performance for the detection of PCa.

Multiparametric MRI may Help to Identify Patients With Prostate Cancer in a Contemporary Cohort of Patients With Clinical Bladder Outlet Obstruction Scheduled for Holmium Laser Enucleation of the Prostate (HoLEP).

Objective: To investigate the value of standard [digital rectal examination (DRE), PSA] and advanced (mpMRI, prostate biopsy) clinical evaluation for prostate cancer (PCa) detection in contemporary patients with clinical bladder outlet obstruction (BOO) scheduled for Holmium laser enucleation of the prostate (HoLEP).Material and Methods: We retrospectively analyzed 397 patients, who were referred to our tertiary care laser center for HoLEP due to BOO between 11/2017 and 07/2020. Of those, 83 (20.7%) underwent further advanced clinical PCa evaluation with mpMRI and/or prostate biopsy due to elevated PSA and/or lowered PSA ratio and/or suspicious DRE. Logistic regression and binary regression tree models were applied to identify PCa in BOO patients.Results: An mpMRI was conducted in 56 (66%) of 83 patients and revealed PIRADS 4/5 lesions in 14 (25%) patients. Subsequently, a combined systematic randomized and MRI-fusion biopsy was performed in 19 (23%) patients and revealed in PCa detection in four patients (5%). A randomized prostate biopsy was performed in 31 (37%) patients and revealed in PCa detection in three patients (4%). All seven patients (9%) with PCa detection underwent radical prostatectomy with 29% exhibiting non-organ confined disease. Incidental PCa after HoLEP (n = 76) was found in nine patients (12%) with advanced clinical PCa evaluation preoperatively. In univariable logistic regression analyses, PSA, fPSA ratio, and PSA density failed to identify patients with PCa detection. Conversely, patients with a lower International Prostate Symptom Score (IPSS) and PIRADs 4/5 lesion in mpMRI were at higher risk for PCa detection. In multivariable adjusted analyses, PIRADS 4/5 lesions were confirmed as an independent risk factor (OR 9.91, p = 0.04), while IPSS did not reach significance (p = 0.052).Conclusion: In advanced clinical PCa evaluation mpMRI should be considered in patients with elevated total PSA or low fPSA ratio scheduled for BOO treatment with HoLEP. Patients with low IPSS or PIRADS 4/5 lesions in mpMRI are at highest risk for PCa detection. In patients with a history of two or more sets of negative prostate biopsies, advanced clinical PCa evaluation might be omitted.

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.

LMTK2 as Potential Biomarker for Stratification between Clinically Insignificant and Clinically Significant Prostate Cancer.

A set of prostate tumors tend to grow slowly and do not require active treatment. Therefore, stratification between patients with clinically significant and clinically insignificant prostate cancer (PC) remains a vital issue to avoid overtreatment. Fast development of genetic technologies accelerated development of next-generation molecular tools for reliable PC diagnosis. The aim of this study is to evaluate the diagnostic value of molecular biomarkers (CRISP3, LMTK2, and MSMB) for separation of PC cases from benign prostatic changes and more specifically for identification of clinically significant PC from all pool of PC cases in patients with rising PSA levels. Patients (n = 200) who had rising PSA (PSA II) after negative transrectal systematic prostate biopsy due to elevated PSA (PSA I) were eligible to the study. In addition to PSA concentration, PSA density was calculated for each patient. Gene expression level was measured in peripheral blood samples of cases applying RT-PCR, while MSMB (−57 C/T) polymorphism was identified by pyrosequencing. LMTK2 and MSMB significantly differentiated control group from both BPD and PC groups. MSMB expression tended to increase from the major alleles of the CC genotype to the minor alleles of the TT genotype. PSA density was the only clinical characteristic that significantly differentiated clinically significant PC from clinically insignificant PC. Therefore, LMTK2 expression and PSA density were significantly distinguished between clinically significant PC and clinically insignificant PC. PSA density rather than PSA can differentiate PC from the benign prostate disease and, in combination with LMTK2, assist in stratification between clinically insignificant and clinically significant PC.

This Month in Adult Urology

This Month in Adult Urology

Multiparametric MRI-ultrasound fusion prostate biopsy in patients without prior diagnosis of prostate cancer: beyond centers of excellence

Purpose Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion prostate biopsy (FBx) has demonstrated increased accuracy for prostate cancer detection at designated centers of excellence. There is a concern if their results can be reproduced in smaller centers. Here, we evaluate the outcomes of FBx from a smaller academic center. Methods A retrospective review of patients without a prior diagnosis of prostate cancer undergoing FBx from January 2014 to November 2019 was performed. Histopathological results were grouped into low-risk disease (Grade Group 1), intermediate-risk disease (Grade Group 2 and 3), and high-risk disease (Grade Group 4 or 5). Clinically significant (CS) prostate cancer was defined as Grade Group ≥ 2. Results Five hundred and six men were included. Median age (IQR) and PSA (IQR) were 65.2 (60.3–70.2) years and 6.9 (5.2–9.7) ng/ml, respectively. There was no difference in overall cancer detection between FBx and SBx (53.6% vs 56.4% p = .1507). CS cancer detection was significantly higher with FBx (39.6% vs 35.3, p = .0275). FBx also outperformed SBx in diagnosing CS disease in patients with prior history of negative prostate biopsy (36.9% vs 27.9%, p < .001). Conclusion FBx detects a higher proportion of clinically significant disease and a lower proportion of clinically insignificant disease compared to SBx, in line with outcomes demonstrated by centers of excellence.

This Month in Adult Urology

This Month in Adult Urology

Do not underestimate anterior prostate cancer.

With the introduction of magnetic resonance imaging in the diagnosis of prostate cancer and its use in targeted prostate biopsy, an increased incidence of anterior-predominant prostate cancer (APC) has been observed. We enrolled 200 patients who underwent radical prostatectomy at our department between 12/2017 and 04/2019. We evaluated tumour location in the individual segments of the prostate, index tumour location and volume, and compared the postoperative stage, Gleason score, grade group (GG), and the presence of extraprostatic extension (EPE) in APC and posterior prostate cancer (PPC). We assessed the rate of MRI scans prior to prostate surgery as well as the influence of family history and PSA on the presence of APC. We found a significantly higher rate of anterior tumours than previously reported (37%) and confirmed that these tumours are diagnosed with a significantly larger index tumour volume (P=0.003). We also showed that a mere 6.76% of APCs were low-risk tumours not requiring radical treatment. Furthermore, anterior tumours were found significantly more often (P=0.001) in patients who underwent preoperative MRI. No differences were observed between PSA values, family history, presence of EPE, or locally advanced disease in APC vs. PPC. The frequency of anterior tumours is higher than previously thought, and they include tumours requiring radical treatment. When these tumours are neglected, it may lead to patient undertreatment with impact on their life prognosis. Thus, we consider the use of MRI-targeted prostate biopsy to be a necessity both for ruling out APC in the case of repeatedly negative prostate biopsies and, in particular, before patient inclusion in active surveillance.

Selecting Patients with Favorable Risk, Grade Group 2 Prostate Cancer for Active Surveillance-Does Magnetic Resonance Imaging Have a Role?

The National Comprehensive Cancer Network® recommends that selected men with grade group 2 prostate cancer be considered for active surveillance. However, selecting which patients with grade group 2 disease can be safely managed by active surveillance remains controversial. The aim of this study was to evaluate the association of multiparametric magnetic resonance imaging with adverse pathology in the radical prostatectomy specimen of men with favorable risk grade group 2 prostate cancer, which could help select patients for active surveillance. We retrospectively analyzed a cohort of patients with favorable grade group 2 disease who underwent radical prostatectomy between 2010 and 2019. Preoperative multiparametric magnetic resonance imaging was scored as negative (no identifiable lesion), positive (identifiable lesion) or equivocal. We defined a multivariable logistic regression model with multiparametric magnetic resonance imaging score as the predictor and adverse pathology (up staging to T3a/b disease, upgrading to ≥grade group 3 or lymph node invasion) as the outcome, adjusting for preoperative prostate specific antigen, biopsy Gleason grade, clinical stage, and number of negative and positive prostate biopsy cores. Secondary outcomes of biochemical recurrence, grade group upgrading alone and the added value of incorporating multiparametric magnetic resonance imaging data into the nomogram were also investigated. We identified 1,117 patients with favorable risk grade group 2 disease who underwent radical prostatectomy. Positive multiparametric magnetic resonance imaging was associated with higher rates of adverse pathology (OR 2.55, 95% CI 1.75-3.40, p <0.0001) and upgrading (OR 3.89, 95% CI 2.00-7.56, p <0.0001). However, as our study included only grade group 2 patients who underwent radical prostatectomy, our cohort may represent a higher risk group than grade group 2 patients as a whole. Adding multiparametric magnetic resonance imaging results to a standard prediction model led to higher net benefit on decision curve analysis. An identifiable lesion on multiparametric magnetic resonance imaging was associated with an increased risk of aggressive pathological features in the radical prostatectomy specimen of patients with favorable risk grade group 2 prostate cancer who were potential active surveillance candidates. This information could be used to inform biopsy strategy, counsel patients on treatment options and guide strategies for those on active surveillance. Combining multiple magnetic resonance imaging modalities (multiparametric magnetic resonance imaging) provides a more accurate prediction of the risk presented by prostate cancer than current prediction methods. In this study, positive magnetic resonance imaging results approximately doubled the chances that a patient with favorable risk prostate cancer would be found to have adverse pathology when their prostate was removed. Thus, multiparametric magnetic resonance imaging could help select patients with favorable risk cancer who may be good candidates for active surveillance, and help guide biopsy and surveillance strategies for such patients.

The Clinical Significance of Multiple Negative Surveillance Prostate Biopsies for Men on Active Surveillance-Does Cancer Vanish or Simply Hide?

Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known. Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study. Exposure variables were 0, 1 or 2 consecutively negative biopsies after diagnosis. Other variables included age, prostate specific antigen, prostate specific antigen density, Gleason grade group, percent positive cores and magnetic resonance imaging findings. Outcome variables were the detection of any cancer at fourth biopsy and active treatment. A total of 514 men were included, with 112 (22%) men having 1 negative biopsy and 78 (15%) with 2 consecutively negative biopsies. Median prostate specific antigen density was lower for men with 1 negative biopsy (0.11) and consecutively negative biopsies (0.10) compared to men who never had a negative biopsy (0.13, p <0.01). On univariable logistic regression higher prostate specific antigen density (OR 1.68, 95% CI 1.16-2.45) and suspicious magnetic resonance imaging lesions (OR 2.00, 95% CI 1.16-3.42) were associated with a higher likelihood of detecting cancer on fourth biopsy. On multivariable logistic regression 1 negative biopsy (OR 0.22, 95% CI 0.12-0.41) and consecutively negative biopsies (OR 0.12, 95% CI 0.06-0.24) were associated with a lower likelihood of detecting cancer at outcome biopsy. Unadjusted 10-year treatment-free survival was highest for patients with consecutively negative biopsies (84%) and 1 negative biopsy (74%) than those who had none (66%) (log rank p=0.02). Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.