Richard Huang

Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion–targeted Prostate Biopsy Outcomes

BACKGROUND Increasing evidence supports the use of magnetic resonance imaging (MRI)-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). OBJECTIVE To compare MRF-TB and SB results and investigate the relationship between biopsy outcomes and prebiopsy MRI. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-mo period. A total of 601 of 803 consecutively eligible men were included. INTERVENTIONS All men were offered prebiopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. OUTCOMES Detection rates for all PCa and high-grade PCa (Gleason score [GS] ≥7) were compared using the McNemar test. RESULTS AND LIMITATIONS MRF-TB detected fewer GS 6 PCas (75 vs 121; p<0.001) and more GS ≥7 PCas (158 vs 117; p<0.001) than SB. Higher mSS was associated with higher detection of GS ≥7 PCa (p<0.001) but was not correlated with detection of GS 6 PCa. Prediction of GS ≥7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS ≥7 PCas in men with no prior biopsy (88 vs 72; p=0.012), in men with a prior negative biopsy (28 vs 16; p=0.010), and in men with a prior cancer diagnosis (42 vs 29; p=0.043). MRF-TB detected fewer GS 6 PCas in men with no prior biopsy (32 vs 60; p<0.001) and men with prior cancer (30 vs 46; p=0.034). Limitations include the retrospective design and the potential for selection bias given a referral population. CONCLUSIONS MRF-TB detects more high-grade PCas than SB while limiting detection of GS 6 PCa in men presenting for prostate biopsy. These findings suggest that prebiopsy multiparametric MRI and MRF-TB should be considered for all men undergoing prostate biopsy. In addition, mSS in conjunction with biopsy indications may ultimately help in identifying men at low risk of high-grade cancer for whom prostate biopsy may not be warranted. PATIENT SUMMARY We examined how magnetic resonance imaging (MRI)-targeted prostate biopsy compares to traditional systematic biopsy in detecting prostate cancer among men with suspicion of prostate cancer. We found that MRI-targeted biopsy detected more high-grade cancers than systematic biopsy, and that MRI performed before biopsy can predict the risk of high-grade cancer.

Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification.

PURPOSE MRF-TB (magnetic resonance imaging-ultrasound fusion targeted prostate biopsy) may improve the detection of prostate cancer in men presenting for prostate biopsy. We report clinical outcomes of 12-core systematic biopsy and MRF-TB in men who presented for primary biopsy and further describe pathological characteristics of cancers detected by systematic biopsy and not by MRF-TB. MATERIALS AND METHODS Clinical outcomes of 452 consecutive men who underwent prebiopsy multiparametric magnetic resonance imaging followed by MRF-TB and systematic biopsy at our institution between June 2012 and June 2015 were captured in an institutional review board approved database. Clinical characteristics, biopsy results and magnetic resonance imaging suspicion scores were queried from the database. RESULTS Prostate cancer was detected in 207 of 382 men (54.2%) with a mean±SD age of 64±8.5 years and mean±SEM prostate specific antigen 6.8±0.3 ng/ml who met study inclusion criteria. The cancer detection rate of systematic biopsy and MRF-TB was 49.2% and 43.5%, respectively (p=0.006). MRF-TB detected more Gleason score 7 or greater cancers than systematic biopsy (117 of 132 or 88.6% vs 102 of 132 or 77.3%, p=0.037). Of 41 cancers detected by systematic biopsy but not by MRF-TB 34 (82.9%) demonstrated Gleason 6 disease, and 26 (63.4%) and 34 (82.9%) were clinically insignificant by Epstein criteria and a UCSF CAPRA (University of California-San Francisco-Cancer of the Prostate Risk Assessment) score of 2 or less, respectively. CONCLUSIONS In men presenting for primary prostate biopsy MRF-TB detects more high grade cancers than systematic biopsy. Most cancers detected by systematic biopsy and not by MRF-TB are at clinically low risk. Prebiopsy magnetic resonance imaging followed by MRF-TB decreases the detection of low risk cancers while significantly improving the detection and risk stratification of high grade disease.

Risk Stratification by Urinary Prostate Cancer Gene 3 Testing Before Magnetic Resonance Imaging-Ultrasound Fusion-targeted Prostate Biopsy Among Men With No History of Biopsy

OBJECTIVE To determine whether a combination of prostate cancer gene 3 (PCA3) and magnetic resonance imaging (MRI) suspicion score (mSS) could further optimize detection of prostate cancer on MRI fusion-targeted biopsy (MRF-TB) among men with no history of biopsy. MATERIALS AND METHODS We included in this study 187 men presenting to our institution between June 2012 and August 2014 who underwent multiparametric MRI (mpMRI) and PCA3 before MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics curves and multivariable logistic regressions were used to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (area under the curve: 0.67, 95% confidence interval: 0.59-0.76). Using a cutoff of ≥35, PCA3 was associated with cancer risk among men with mSS 2-3 (P = .004), but not among those with mSS 4-5 (P = .340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (area under the curve: 0.83 vs 0.79, P = .0434). CONCLUSION Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high-suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB, adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.

Prediction of Prostate Cancer Risk Among Men Undergoing Combined MRI-targeted and Systematic Biopsy Using Novel Pre-biopsy Nomograms That Incorporate MRI Findings

OBJECTIVE To develop nomograms that predict the probability of overall prostate cancer (PCa) and clinically significant PCa (Gleason ≥7) on magnetic resonance imaging (MRI)-targeted, and combined MRI-targeted and systematic, prostate biopsy. MATERIALS AND METHODS From June 2012 to August 2014, magnetic resonance imaging to ultrasound fusion-targeted prostate biopsy was performed on 464 men with suspicious regions identified on pre-biopsy 3T MRI along with systematic 12 core biopsy. Logistic regression modeling was used to evaluate predictors of overall and clinically significant PCa, and corresponding nomograms were generated for men who were not previously biopsied or had 1 or more prior negative biopsies. Models were created with 70% of a randomly selected training sample and bias-corrected using bootstrap resampling. The models were then validated with the remaining 30% testing sample pool. RESULTS A total of 459 patients were included for analysis (median age 66 years, prostate-specific antigen [PSA] 5.2 ng/mL, prostate volume 49 cc). Independent predictors of PCa on targeted and systematic prostate biopsy were PSA density, age, and MRI suspicion score. PCa probability nomograms were generated for each cohort using the predictors. Bias-corrected areas under the receiver-operating characteristic curves for overall and clinically significant PCa detection were 0.82 (0.78) and 0.91 (0.84) for men without prior biopsy and 0.76 (0.65) and 0.86 (0.87) for men with a prior negative biopsy in the training (testing) samples. CONCLUSION PSA density, age, and MRI suspicion score predict PCa on combined MRI-targeted and systematic biopsy. Our generated nomograms demonstrate high diagnostic accuracy and may further aid in the decision to perform biopsy in men with clinical suspicion of PCa.

The Institutional Learning Curve of Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy: Temporal Improvements in Cancer Detection in 4 Years

Purpose While magnetic resonance imaging‐ultrasound fusion targeted biopsy allows for improved detection of clinically significant prostate cancer, a concerning amount of clinically significant disease is still missed. We hypothesized that a number of these misses are due to the learning curve associated with magnetic resonance imaging‐ultrasound fusion targeted biopsy. We report the results of repeat magnetic resonance imaging‐ultrasound fusion targeted biopsy in men with continued suspicion for cancer and the institutional learning curve in the detection of clinically significant prostate cancer with time. Materials and Methods We analyzed the records of 1,813 prostate biopsies in a prospectively acquired cohort of men who presented for prostate biopsy in a 4‐year period. All men were offered prebiopsy magnetic resonance imaging and were assigned a maximum PI‐RADS™ (Prostate Imaging Reporting and Data System version 2) score. Biopsy outcomes in men with a suspicious region of interest were compared. The relationship between time and clinically significant prostate cancer detection was analyzed. Results The clinically significant prostate cancer detection rate increased 26% with time in men with a PI‐RADS 4/5 region of interest. On repeat magnetic resonance imaging‐ultrasound fusion targeted biopsy in men with continued suspicion for cancer 53% of those with a PI‐RADS 4/5 region of interest demonstrated clinically significant discordance from the initial magnetic resonance imaging‐ultrasound fusion targeted biopsy compared to only 23% with a PI‐RADS 1/2 region of interest. Significantly less clinically significant prostate cancer was missed or under graded in the most recent biopsies compared to the earliest biopsies. Conclusions The high upgrade rate on repeat magnetic resonance imaging‐ultrasound fusion targeted biopsy and the increasing cancer detection rate with time show the significant learning curve associated with magnetic resonance imaging‐ultrasound fusion targeted biopsy. Men with low risk or negative biopsies with a persistent, concerning region of interest should be promptly rebiopsied. Improved targeting accuracy with operator experience can help decrease the number of missed cases of clinically significant prostate cancer.

Predicting Benign Prostate Pathology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy in Men with a Prior Negative 12-core Systematic Biopsy: External Validation of a Prognostic Nomogram

BACKGROUND Magnetic resonance imaging (MRI) of the prostate after a prior negative biopsy may reduce the need for unnecessary repeat biopsies. OBJECTIVE To externally validate a previously developed nomogram predicting benign prostate pathology on MRI/ultrasound (US) fusion-targeted biopsy in men with a Prostate Imaging Reporting and Data System (PI-RADS) 3-5 region of interest and a prior negative 12-core systematic biopsy, and update this nomogram to improve its performance. DESIGN, SETTING, AND PARTICIPANTS A total of 2063 men underwent MRI/US fusion-targeted biopsy from April 2012 to September 2017; 104 men with a negative systematic biopsy followed by MRI-US fusion-targeted biopsy of a PI-RADS 3-5 region of interest (58%) met the study inclusion criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An MRI-based nomogram that had previously been developed in a multi-institutional clinical setting was externally validated. Predictive characteristics were age, prostate volume, MRI PI-RADS score, and prostate-specific antigen (PSA). Bayesian logistic regression was used to update the previous model. RESULTS AND LIMITATIONS Median age of the external validation cohort was 68 yr, PSA was 7.2ng/ml, and biopsy confirmed benign pathology in 30% (n=31), suggesting a lower baseline risk compared with the nomogram development cohort. Receiver operating characteristic curve analysis showed areas under curve (AUCs) from 0.77 to 0.80 for nomogram validation. An updated model was constructed with improved calibration and similar discrimination (AUC 0.79). CONCLUSIONS Age, prostate volume, PI-RADS, and PSA predict benign pathology on MRI/US fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy. The validated and updated nomogram demonstrated high diagnostic accuracy and may further aid in the decision to avoid a biopsy in men with a prior negative biopsy. PATIENT SUMMARY We externally validated a clinically useful tool that predicts benign prostate pathology on magnetic resonance imaging/ultrasound fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy and updated this predictive tool to improve its performance in patient counseling regarding the need for a repeat biopsy.

PD61-05 OUTCOMES OF REPEAT MRI-US FUSION-TARGETED BIOPSY IN MEN WITH INITIALLY LOW RISK OR NEGATIVE FUSION BIOPSY

underwent only TRUS systematic random biopsies versus US-MRI FB for PCa. METHODS: A retrospective analysis of patients0 prospective collected data that underwent prostate biopsy and subsequent radical prostatectomy were included from January 2011 to June 2016 at our institution. The study cohort was divided into: US-MRI FB (Group A) and only TRUS systematic random biopsy (Group B). US-MRI FB was performed in patients who had a previous MRI with a focal lesion classified by Likert score 3, otherwise a TRUS systematic random biopsy was performed. All biopsies and surgical specimens were analyzed by the same uropathologist and MRIs were analyzed by two expert urological radiologists. RESULTS: 73 men underwent US-MRI FB and 89 TRUS systematic random biopsy. The GU rate was higher in group B (31.5% vs 16.4%; p 1⁄4 0.027). GU according to Gleason grade pattern was higher in Group B against Group A (40.4% vs 23.3%; p 1⁄4 0.02). Analyses from separate Gleason grade pattern showed that Gleason score 3+4 presented less GU in group A (24.1% vs 52.6%; p 1⁄4 0.043)(table 1). The Bland-Altman plot analysis showed a higher bias in Group B compared to group A (-0.27 [-1.40 to 0.86] vs -0.01 [-1.42 to 1.39]). In the multivariable logistic regression the only independent predictor of GU was the use of TRUS systematic random biopsy (2.64 [1.11 6.28]; p 1⁄4 0.024). CONCLUSIONS: The US-MRI FB appears to be related to a decrease in GU rate and an increase in the concordance between biopsy and final pathology in comparison to TRUS random biopsy, that leads to greater accuracy on diagnosis and better treatment decision.

MP38-13 OUTCOMES OF MRI-US FUSION-TARGETED BIOPSY IN MEN WITH NO PREVIOUS BIOPSY: OPPORTUNITY TO REDUCE BIOPSY UTILIZATION AND SECONDARY OVER-DETECTION

METHODS: From a single institution database, 2,201 patients were identified who underwent both prostate biopsy and RP between 2006 and 2016. Propensity score matching was performed with the nearest neighbor method using R-programming version 3.3.1 and a 4:1 match ratio. A total of 101 men were identified who underwent MRITRUS plus standard template biopsies were subsequently matched to 404 men who underwent untargeted extended template TRUS biopsy. Matched covariates included age at diagnosis, initial prostate specific antigen (PSA), race, clinical stage, total number of cores retrieved at time of biopsy, and history of prior TRUS biopsy. Continuous variables were compared using Wilcoxon rank-sum tests and categorical variables were assessed with c2 test. The concordance of Gleason score from biopsy to RP was assessed. RESULTS: After propensity score matching, median age was 64 years (IQR 59.5-68.5), median PSA was 5.4 ng/mL (IQR 4.0-8.1), median prostate size was 48 grams (IQR 38.5-60), and median number of cores retrieved at time of biopsy was 15 (IQR 12-20). Of patients who received MRI-TRUS plus standard template biopsy, 67 of 99 (67.7%) showed concordant Gleason grading between biopsy and RP pathology, whereas 204 of 397 (51.4%) of extended template TRUS biopsy patients were concordant (p<0.01). Fewer MRI-TRUS plus standard template biopsy patients were either upgraded (26.3% versus 32.2%) or downgraded (6.1% versus 15.4%) from biopsy to RP (p<0.01). CONCLUSIONS: Of men undergoing TRUS biopsy for the diagnosis of PCa, MRI-TRUS fusion plus standard template techniques have a higher concordance with final pathology at RP. Additionally, MRI-TRUS techniques demonstrated better accuracy with lower rates of upgrading and downgrading prostatectomy when compared to untargeted extended template TRUS biopsy independent of total number of cores taken.

MP77-18 OUTCOMES OF MRI-US FUSION TARGETED PROSTATE BIOPSY IN MEN WITH HISTORY OF PROSTATIC INTRAEPITHELIAL NEOPLASIA AND/OR ATYPICAL SMALL ACINAR PROLIFERATION: EVIDENCE FOR AN ALTERATION OF CURRENT PRACTICE.

INTRODUCTION AND OBJECTIVES: While PCA3 has been shown to be predictive of prostate cancer (CaP) detection in the setting of systematic biopsy (SB), performance in the setting of targeted MRI-ultrasound fusion biopsy (MRF-TB) is not well described. METHODS: Biopsy results in all men undergoing both SB and MRF-TB, using the Artemis/Pro fuse system, between June 2012 and June 2014 were reviewed. PCA3 scores, highest MRI suspicion score (mSS), and cancer detection rates were extracted from 143 patients without a previous cancer diagnosis. Receiver operating characteristics (ROC) were analyzed to determine the performance of PCA3 in predicting cancer on MRF-TB at varying thresholds. In bivariable analyses, the association between elevated PCA3 and MRF-TB findings were analyzed. The predictive capability of PCA3þmSS was compared to that of mSS alone by fitting multivariable logistic regression models and comparing ROC and areas under the curve (AUC). RESULTS: Table 1 summarizes the predictive capability for Gleason 3þ3 or higher disease on MRF-TB, stratified by threshold. In bivariable analyses using a threshold of 35, a greater proportion of those with a high PCA3 demonstrated cancer on MRF-TB than those with a low PCA3 (46.8% vs. 18.8%, p < 0.001). Similarly, patients with a high PCA3 and mSS 3 were more likely to have cancer on MRF-TB than those with a low PCA3 and mSS 3 (48.8% vs. 26.7%, p 1⁄4 0.004). In multivariable analyses, a logistic regression model containing both PCA3 and mSS was associated with significantly higher discrimination of cancer on MRF-TB compared to a model of mSS alone (AUC 0.786 vs. 0.741, p 1⁄4 0.038). Potential study cohort outcomes by threshold are detailed in Table 2 CONCLUSIONS: The predictive capability of PCA3 for prostate cancer is retained in the setting of MRF-TB. Addition of PCA3 to mSS would improve the overall diagnostic accuracy of MRF-TB, but further work is needed to determine the impact of PCA3 at individual thresholds.

PD32-01 COMPARISON OF MRI-US FUSION TARGETED BIOPSY AND SYSTEMATIC PROSTATE BIOPSY: SINGLE INSTITUTION EXPERIENCE IN 604 PATIENTS.

INTRODUCTION AND OBJECTIVES: The aim of the study was to compare partial cystectomy (PC) and radical cystectomy (RC) with respect to 90-day mortality as well as long-term, all cause (ACM) and cancer specific mortality (CSM). METHODS: Using the SEER-Medicare database 3913 patients with T2-T3 urothelial carcinoma of the urinary bladder (UCUB) who underwent either RC (n1⁄43419) or PC (n1⁄4494) were identified. After propensity score matching to reduce potential treatment selection bias, 90day mortality, ACM-free and CSM-free rates between patients treated with PC and RC were estimated. Multivariable regression models (MVA) addressed 90-day mortality as well as 5-years ACM and CSM. RESULTS: After matching, 33% (n1⁄4494) and 67% (n1⁄4988) patients treated respectively with PC or RC remained. Median follow-up was 26months. The 90-daymortality rate was 3.2% (n1⁄416) after PC and 8.1% (n1⁄480) after RC (p1⁄40.001). In MVA, PC vs. RC was associated with a lower 90-day mortality (p<0.001). At 5 years the ACM-free survival rate was 38% after PC and 40% after RC (p1⁄40.3) and failed to differ in MVA (p1⁄40.9). At 5 years the CSM-free survival rate was 59%after PC and 62% after RC (p1⁄40.2) and also failed to differ in MVA (p1⁄40.57). The same results were observed after restriction to patients with pT2N0 UCUB. CONCLUSIONS: Relative to RC, PC is associated with lower short-term mortality and the same long-term ACM and CSM rates. These observations should encourage greater consideration to PC in those selected cases when this type of surgery may be applied.