Fusion-guided Prostate Biopsy Research Articles

Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine.

Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy.

Comparison of Multiparametric MRI Scoring Systems and the Impact on Cancer Detection in Patients Undergoing MR US Fusion Guided Prostate Biopsies.

IntroductionMultiple scoring systems have been proposed for prostate MRI reporting. We sought to review the clinical impact of the new Prostate Imaging Reporting and Data System v2 (PI-RADS) and compare those results to our proposed Simplified Qualitative System (SQS) score with respect to detection of prostate cancers and clinically significant prostate cancers.MethodsAll patients who underwent multiparametric prostate MRI (mpMRI) had their images interpreted using PI-RADS v1 and SQS score. PI-RADS v2 was calculated from prospectively collected data points. Patients with positive mpMRIs were then referred by their urologists for enrollment in an IRB-approved prospective phase III trial of mpMRI-Ultrasound (MR/TRUS) fusion biopsy of suspicious lesions. Standard 12-core biopsy was performed at the same setting. Clinical data were collected prospectively.Results1060 patients were imaged using mpMRI at our institution during the study period. 341 participants were then referred to the trial. 312 participants underwent MR/TRUS fusion biopsy of 452 lesions and were included in the analysis. 202 participants had biopsy-proven cancer (64.7%) and 206 (45.6%) lesions were positive for cancer. Distribution of cancer detected at each score produced a Gaussian distribution for SQS while PI-RADS demonstrates a negatively skewed curve with 82.1% of cases being scored as a 4 or 5. Patient-level data demonstrated AUC of 0.702 (95% CI 0.65 to 0.73) for PI-RADS and 0.762 (95% CI 0.72 to 0.81) for SQS (p< 0.0001) with respect to the detection of prostate cancer. The analysis for clinically significant prostate cancer at a per lesion level resulted in an AUC of 0.725 (95% CI 0.69 to 0.76) and 0.829 (95% CI 0.79 to 0.87) for the PI-RADS and SQS score, respectively (p< 0.0001).ConclusionsmpMRI is a useful tool in the workup of patients at risk for prostate cancer, and serves as a platform to guide further evaluation with MR/TRUS fusion biopsy. SQS score provided a more normal distribution of scores and yielded a higher AUC than PI-RADS v2. However until our findings are validated, we recommend reporting of detailed sequence-specific findings. This will allow for prospectively collected data to be utilized in determining the impact of ongoing changes to these scoring systems as our understanding of mpMRI interpretation evolves.

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies—Are We Gaining in Accuracy?

We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade.

Comparison of patient comfort between MR-guided in-bore and MRI/ultrasound fusion-guided prostate biopsies within a prospective randomized trial.

The objective of this study was to compare patient comfort between MR-guided in-bore prostate biopsy (IB-GB) and MRI/ultrasound fusion-guided prostate biopsy (FUS-GB) with additional systematic 12-core transrectal ultrasound (TRUS)-guided biopsy within a prospective randomized trial. Two hundred and ten consecutive patients were randomly assigned in a 1:1 ratio to receive either IB-GB and prior intrarectal instillation of a 2% lidocaine gel (n = 106) or FUS-GB plus additional systematic 12-core TRUS-guided biopsy and prior application of a periprostatic nerve block (PPNB) with 2% mepivacaine (n = 104). The maximal procedural pain (MPP) on a 0-10 visual analog scale and the operating room time were recorded for each biopsy session. Baseline characteristics and mean number of targeted biopsy cores (5.6 ± 0.8 vs 5.4 ± 1.2 for IB-GB and FUS-GB, respectively; p = 0.278) were similar in both study arms. In relation to the IB-GB arm, the total number of biopsy cores in the FUS-GB arm, including the systematic 12-core TRUS-guided biopsy, was significantly higher (17.4 ± 1.2; p < 0.001). Patients with IB-GB had significantly higher MPP scores (2.95 ± 2.15) compared with subjects with FUS-GB (1.95 ± 1.56; p < 0.001). FUS-GB required significantly less time (28.22 ± 11.61 min) in comparison with IB-GB (42.09 ± 11.37 min; p < 0.001). The PPNB can easily be administered just prior to performing FUS-GB. Thus, patients have significantly lower pain levels in comparison with IB-GB, which is usually done with intrarectal anesthetic gels. Although the addition of a systematic 12-core TRUS-guided biopsy significantly increases the number of biopsy cores, FUS-GB still requires significantly less time in comparison with IB-GB.

The role of MRI in active surveillance for prostate cancer.

Approximately one in seven American men will be diagnosed with prostate cancer during his lifetime, and at least 50% of newly diagnosed patients will present with low-risk disease. In the last decade, the decision-making paradigm for management has shifted due to high rates of disease detection and overtreatment, attributed to prostate-specific antigen screening, with more men deferring definitive treatment for active surveillance. The advent of multiparametric magnetic resonance imaging (MP-MRI) and MRI/ transrectal ultrasound-guided fusion-guided prostate biopsy has refined the process of diagnosis, identifying patients with clinically-significant cancer and larger disease burden who would most likely benefit from intervention. In parallel, the utilization of MP-MRI in the surveillance of low-grade, low-volume disease is on the rise, reflecting support in a growing body of literature. The aim of this review is to appraise and summarize the data evaluating the role of magnetic resonance imaging in active surveillance for prostate cancer.

Prostate cancer: MR-TRUS fusion biopsy--defining a new standard.

The widespread use of PSA screening and transrectal ultrasound (TRUS)-guided prostate biopsy has resulted in an epidemic of overdetection and overtreatment of prostate cancer. The use of targeted magnetic resonance (MR) and ultrasound fusion guided prostate biopsy promises to improve the detection rate of high-risk prostate cancer—reducing the issue of overdetection and overtreatment.

MP17-09 TRENDS IN CANCER DETECTION RATE AND COMPLICATIONS AFTER MAGNETIC RESONANCE IMAGING-ULTRASOUND (MRI/US) FUSION-GUIDED PROSTATE BIOPSIES

You have accessJournal of UrologyImaging/Radiology: Uroradiology III1 Apr 2015MP17-09 TRENDS IN CANCER DETECTION RATE AND COMPLICATIONS AFTER MAGNETIC RESONANCE IMAGING-ULTRASOUND (MRI/US) FUSION-GUIDED PROSTATE BIOPSIES Simpa Salami, Oksana Yaskiv, Baris Turkbey, Robert Villani, Eran Ben-Levi, and Ardeshir Rastinehad Simpa SalamiSimpa Salami More articles by this author , Oksana YaskivOksana Yaskiv More articles by this author , Baris TurkbeyBaris Turkbey More articles by this author , Robert VillaniRobert Villani More articles by this author , Eran Ben-LeviEran Ben-Levi More articles by this author , and Ardeshir RastinehadArdeshir Rastinehad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.851AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We hypothesized that as the quality of MRI interpretation and experience improves, the procedure duration and cancer detection rate (CDR) of Magnetic Resonance Imaging-Ultrasound (MRI/US) Fusion-Guided Prostate Biopsies will improve. METHODS We prospectively enrolled men with abnormal PSA and/or DRE, or on AS for CaP who underwent a 3T mpMRI (T2, DWI, and DCE) with an endorectal coil. Three radiologists (EB, RV, AR) reviewed and graded all lesions using the 5-point Likert scale as proposed by European Symposium on Urogenital Radiology, 2012. The UroNav system (Invivo, Florida ®) was used to perform MR/TRUS fusion-guided prostate biopsies under local anesthesia, obtaining one biopsy core in axial and sagittal planes from each lesion. A 12-core biopsy was performed at the same setting. All biopsies were performed by a fellowship-trained urologic oncologist with experience with fusion biopsies. Our institution's pathologist reviewed all biopsy slides. We divided the cohort into equal quartiles based on date of enrollment. We estimate the CDR, mean procedure time, and complication rate. RESULTS A total of 376 men were eligible for analysis. The median age and PSA were 65.2 years and 6.6 ng/mL respectively. The overall CDR was 66% (248/376). Suspicion score on mpMRI was positively correlated with detection of CaP (p<0.0001); 100% of those with a suspicion score of 5 had clinically significant CaP. The CDR for the 1st, 2nd, 3rd, and 4th quartiles (each n = 94) were 73.4%, 62.8%, 71.3%, 56.4% respectively (M-H p-value = 0.052). The mean procedure times for each quartile were 16, 17, 14, and 14 minutes respectively. The complications were: urinary tract infections/sepsis (2.7%) and urinary retention (1.3%). CONCLUSIONS We report that the CDR of fusion biopsy does not change significantly over time in the hands of an experienced urologist. The procedure time appears to improve with experience. Fusion biopsy is not associated with significant increase in complication risks compared with the general population. Further studies are needed to determine the learning curve in an inexperienced hands. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e179 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Simpa Salami More articles by this author Oksana Yaskiv More articles by this author Baris Turkbey More articles by this author Robert Villani More articles by this author Eran Ben-Levi More articles by this author Ardeshir Rastinehad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

761 A prospective randomized study comparing MR-guided in-bore versus MRI/ultrasound fusionguided prostate biopsy in patients with prior tumor-negative TRUS biopsy

761 A prospective randomized study comparing MR-guided in-bore versus MRI/ultrasound fusionguided prostate biopsy in patients with prior tumor-negative TRUS biopsy

Use of multiparametric MRI to alter management pathways: Treatment patterns of prostate cancer in the targeted biopsy era.

56 Background: As the use of multiparametric MRI (mpMRI) to diagnose prostate cancer (PCa) becomes established, better knowledge of treatment patterns is needed to counsel patients. Prior studies have shown 40-55% undergo Radical Prostatectomy (RP), while only 6% prefer Active Surveillance (AS), and that stratification by risk does not greatly alter treatment pathways. We aim to delineate the distribution of PCa treatment modalities in the MRI/US fusion-guided prostate biopsy (FB) era. Methods: A retrospective review was performed of all patients who underwent FB at the NIH from 2010 to present. Demographics, Gleason scores, MRI Suspicion scores and treatment outcomes were recorded. Patients were stratified according to D’Amico Risk Criteria, and outcomes were coded into four categories: AS; RP; Radiation (XRT, Brachytherapy); and Other (Systemic or Focal therapy). Results: 839 men were reviewed. Mean age was 62.6 years old and mean PSA was 9.7 ng/mL. Total cancer detection rate was 70% (n = 589). Of FB positive men, 474 had treatment information available. Overall 225 (47.5%) entered AS, 158 (33.3%) underwent RP, 61 (12.9%) received XRT, and 30 (6.3%) received other intervention. Subgroup analysis by MRI suspicion score (Table) showed 47.4% frequency of RP in the high vs. 30.9% and 19.4% for moderate and low suspicion groups, respectively. Analysis by D’Amico Risk (Table) showed 86% of low risk men chose AS vs. 0% of high risk men. Conversely 9.7% of low, 44.5% of intermediate and 55.7% of high risk men underwent RP. Conclusions: FB was associated with a higher rate of AS choice as a treatment modality for low risk disease. However most patients with clinically significant PCa still chose RP as their treatment. FB is an additional tool that allows the urologist to better counsel patients and provides individualized treatment for PCa. [Table: see text]

Correlation of apparent diffusion coefficients (ADCs) on diffusion-weighted (DW) magnetic resonance (MR) imaging with lesion size and prostate cancer risk.

48 Background: A negative correlation between ADC values and Gleason risk of prostate cancer (CaP) has been reported by the NIH. We correlate ADC values on DW MR imaging with lesion size and risk stratification of CaP. Methods: Men with abnormal DRE or PSA underwent a 3T MP-MRI (T2, DWI, and DCE) with an endorectal coil. ADC maps were calculated using b values of 0, 500, 1,000 and 1,500; additional b 2000 images were obtained separately. Three radiologists (EB, RV, AR) reviewed and graded all lesions using the 5-point Likert scale and PI-RADS score. A total of 268 men with suspicious lesion (s) on MRI were prospectively enrolled. The UroNav system (Invivo, Florida) was used to perform MR/TRUS fusion-guided prostate biopsies, obtaining one biopsy core in axial and sagittal planes from each lesion. Our institution’s pathologist reviewed all biopsies. Lowest ADC values of suspicious lesions were correlated against lesion size and Gleason risk stratification. Results: The median age and PSA were 65.0 years and 7.4 ng/mL respectively. An average of 1.5 (378/256) suspicious lesions per patient was identified on the MP-MRI. Median volume of MRI target lesions was 0.36 cm3. The cancer detection rate of fusion biopsy on lesion level analysis was 45.2 % (171/378). The mean ± SD ADC values (x 10-6 mm2/sec) for lesions negative and positive for CaP were 1022 ± 260 and 724 ± 223 respectively (p &lt;0.0001). The mean ± SD ADC values (x 10-6 mm2/sec) for lesion size &lt; 0.2 cm3, 0.2 – 0.5 cm3, 0.5 – 1.0 cm3, and &gt; 1 cm3 were 771 ± 246, 677 ± 206, 629 ± 119, and 500 ± 86respectively. Higher risk CaP was associated with lower ADC values with AUC of 0.77 (p=0.0001). The mean ± SD ADC values (x 10-6 mm2/sec) for low (≤6), intermediate (7), and high (8-10) Gleason grade CaP were 845 ± 285, 687± 195, and 628 ± 145 respectively. Conclusions: The ADC value of suspicious lesions on MRI has an inverse correlation with lesion size and prostate cancer risk. It may be a useful in predicting CaP and its clinical significance. Further studies are needed to determine its value in stratifying patients for prostate biopsy, active surveillance and/or treatment.

Clinical Implications of a Multiparametric Magnetic Resonance Imaging Based Nomogram Applied to Prostate Cancer Active Surveillance

Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. We applied a previously generated nomogram based on multiparametric magnetic resonance imaging to predict active surveillance eligibility based on repeat biopsy outcomes. We reviewed the records of 85 patients who met active surveillance criteria at study entry based on initial biopsy and who then underwent 3.0 Tesla multiparametric magnetic resonance imaging with subsequent magnetic resonance imaging/ultrasound fusion guided prostate biopsy between 2007 and 2012. We assessed the accuracy of a previously published nomogram in patients on active surveillance before confirmatory biopsy. For each cutoff we determined the number of biopsies avoided (ie reliance on magnetic resonance imaging alone without rebiopsy) over the full range of nomogram cutoffs. We assessed the performance of the multiparametric magnetic resonance imaging active surveillance nomogram based on a decision to perform biopsy at various nomogram generated probabilities. Based on cutoff probabilities of 19% to 32% on the nomogram the number of patients who could be spared repeat biopsy was 27% to 68% of the active surveillance cohort. The sensitivity of the test in this interval was 97% to 71% and negative predictive value was 91% to 81%. Multiparametric magnetic resonance imaging based nomograms may reasonably decrease the number of repeat biopsies in patients on active surveillance by as much as 68%. Analysis over the full range of nomogram generated probabilities allows patient and caregiver preference based decision making on the risk assumed for the benefit of fewer repeat biopsies.

Recent Developments in Multiparametric Prostate MR Imaging

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has become a mature and accepted technology in the evaluation of the patient with suspected prostate cancer (PCa). This review focuses on key recent developments in the area of mpMRI, specifically: reporting systems used by radiologists when interpreting mpMRI, advances in technical aspects of diffusion-weighted imaging (DWI), and innovations in MRI-ultrasound (MRI-US) fusion-guided prostate biopsies. These topics were selected given that reporting systems are critical when communicating findings on mpMRI of the prostate to referring clinicians, advanced techniques in DWI have improved the detection and characterization of PCa, and MRI-US fusion biopsies now enable more accurate targeting of suspicious lesions at biopsy, including lesions that are difficult to visualize using standard B-mode ultrasound imaging. Radiologists interpreting prostate MRI today are likely to incorporate aspects of all three of these topics into their current practice.

Diagnostic value of biparametric magnetic resonance imaging (MRI) as an adjunct to prostate-specific antigen (PSA)-based detection of prostate cancer in men without prior biopsies.

To determine the diagnostic yield of analysing biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) for prostate cancer detection compared with standard digital rectal examination (DRE) and prostate-specific antigen (PSA)-based screening. Review of patients who were enrolled in a trial to undergo multiparametric-prostate (MP)-MRI and MR/ultrasound fusion-guided prostate biopsy at our institution identified 143 men who underwent MP-MRI in addition to standard DRE and PSA-based prostate cancer screening before any prostate biopsy. Patient demographics, DRE staging, PSA level, PSA density (PSAD), and B-MRI findings were assessed for association with prostate cancer detection on biopsy. Men with detected prostate cancer tended to be older, with a higher PSA level, higher PSAD, and more screen-positive lesions (SPL) on B-MRI. B-MRI performed well for the detection of prostate cancer with an area under the curve (AUC) of 0.80 (compared with 0.66 and 0.74 for PSA level and PSAD, respectively). We derived combined PSA and MRI-based formulas for detection of prostate cancer with optimised thresholds. (i) for PSA and B-MRI: PSA level + 6 x (the number of SPL) > 14 and (ii) for PSAD and B-MRI: 14 × (PSAD) + (the number of SPL) >4.25. AUC for equations 1 and 2 were 0.83 and 0.87 and overall accuracy of prostate cancer detection was 79% in both models. The number of lesions positive on B-MRI outperforms PSA alone in detection of prostate cancer. Furthermore, this imaging criteria coupled as an adjunct with PSA level and PSAD, provides even more accuracy in detecting clinically significant prostate cancer.

The Role of Image Guided Biopsy Targeting in Patients with Atypical Small Acinar Proliferation

Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer.

The Prostate Cancer Prevention Trial risk calculator for high-grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in predicting men at risk of CaP. Men with an abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate biopsy system, after which 12-core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP-MRI in predicting clinically significant CaP. Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high-grade CaP (all P < .05). The area under the receiver operating characteristic curve of PCPTHG for predicting high-grade CaP was 0.676 (95% confidence interval [CI], 0.592-0.751). By using a risk cutoff of ≥15% for biopsy as, proposed previously for high-grade CaP, sensitivity was 96.4%, specificity was 7.6%, and the false-positive rate was 51.1%. In contrast, the area under the receiver operating characteristic curve of MP-MRI for high-grade CaP was 0.769 (95% CI, 0.703-0.834), and it was 0.812 (95% CI, 0.754-0.869) for clinically significant CaP. MP-MRI outperforms PCPTHG in predicting clinically significant CaP, and its application may help select patients who will benefit from CaP diagnosis and treatment.

Imaging and pathology findings after an initial negative MRI-US fusion-guided and 12-core extended sextant prostate biopsy session

A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study. We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each. The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate-specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease. In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (≤ 3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.

Targeted Prostate Biopsy to Select Men for Active Surveillance: Do the Epstein Criteria Still Apply?

Established in 1994, the Epstein histological criteria (Gleason score 6 or less, 2 or fewer cores positive and 50% or less of any core) have been widely used to select men for active surveillance. However, with the advent of targeted biopsy, which may be more accurate than conventional biopsy, we reevaluated the likelihood of reclassification upon confirmatory rebiopsy using multiparametric magnetic resonance imaging-ultrasound fusion. We identified 113 men enrolled in active surveillance at our institution who met Epstein criteria and subsequently underwent confirmatory targeted biopsy via multiparametric magnetic resonance imaging-ultrasound fusion. Median patient age was 64 years, median prostate specific antigen was 4.2 ng/ml and median prostate volume was 46.8 cc. Targets or regions of interest on multiparametric magnetic resonance imaging-ultrasound fusion were graded by suspicion level and biopsied at 3 mm intervals along the longest axis (median 10.5 mm). Also, 12 systematic cores were obtained during confirmatory rebiopsy. Our reporting is consistent with START (Standards of Reporting for MRI-targeted Biopsy Studies) criteria. Confirmatory fusion biopsy resulted in reclassification in 41 men (36%), including 26 (23%) due to Gleason grade 6 or greater and 15 (13%) due to high volume Gleason 6 disease. When stratified by suspicion on multiparametric magnetic resonance imaging-ultrasound fusion, the likelihood of reclassification was 24% to 29% for target grade 0 to 3, 45% for grade 4 and 100% for grade 5 (p=0.001). Men with grade 4 and 5 vs lower grade targets were greater than 3 times more likely to be reclassified (OR 3.2, 95% CI 1.4-7.1, p=0.006). Upon confirmatory rebiopsy using multiparametric magnetic resonance imaging-ultrasound fusion men with high suspicion targets on imaging were reclassified 45% to 100% of the time. Criteria for active surveillance should be reevaluated when multiparametric magnetic resonance imaging-ultrasound fusion guided prostate biopsy is used.

Diagnostic value of biparametric MRI as an adjunct to PSA-based detection of prostate cancer.

193 Background: To determine the diagnostic yield of analyzing a fast, cost-conscious biparametric (T2 and diffusion-weighted) MRI (B-MRI) for prostate cancer (PCa) detection as an adjunct to to standard digital rectal exam (DRE) and prostate specific antigen (PSA)-based screening. Methods: Review of patients who were enrolled in a trial to undergo MP-MRI and MR/US fusion-guided prostate biopsy at our institution identified 143 men who underwent MP-MRI in addition to standard DRE and PSA-based PCa screening prior to any other prior prostate biopsy sessions. Patient demographics, DRE staging, PSA, PSA density (PSAD), and B-MRI findings were assessed for association with PCa detection on biopsy. Results: Men with detected PCa tended to be older, with higher PSA, higher PSAD, and increased number of screen positive lesions (#SPL) on B-MRI. B-MRI performed well for the detection of PCa with an area under the curve (AUC) of 0.80 (compared to 0.66 and 0.74 for PSA and PSAD). We derived PSA and MRI-based combined screening formulas for detection of PCa with optimized thresholds. (1) for PSA and B-MRI: PSA + 6 x (#SPL) &gt; 14 and (2) for PSAD and B-MRI: 14 x (PSAD) + (#SPL) &gt; 4.25. Area under the curve for equations 1 and 2 were 0.83 and 0.87 and overall accuracy of PCa detection was 79% in both models. Furthermore, the model integrating PSA with #SPL on B-MRI, was much more efficient at maximally identifying men with Gleason 7 or higher disease compared to PSA-screening alone. Use of model combining PSAD and MRI, the number of bGS 7 or higher cancers that were missed was minimized. Overall, combined use of PSA or PSAD coupled with B-MRI #SPL improved the true positive yield of identifying men with bGS 7 or higher while minimizing the false positive number of men identified as “screen-positive,” but with no cancer on biopsy. Conclusions: Number of positive lesions on B-MRI outperforms PSA alone in detecting PCa, supporting the use of this limited, non-contrast MRI as a potential adjunct tool in PCa screening. Furthermore, this imaging criteria coupled as an adjunct with PSA and PSAD, provides even more accuracy in detecting clinically-significant PCa.

Improving Detection of Clinically Significant Prostate Cancer: Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Guided Prostate Biopsy

Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health. We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis. Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p<0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p<0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.

Accuracy of multiparametric magnetic resonance imaging in confirming eligibility for active surveillance for men with prostate cancer

Active surveillance (AS) is an attempt to avoid overtreatment of clinically insignificant prostate cancer (PCa); however, patient selection remains controversial. Multiparametric prostate magnetic resonance imaging (MP-MRI) may help better select AS candidates. We reviewed a cohort of men who underwent MP-MRI with MRI/Ultrasound fusion-guided prostate biopsy and selected potential AS patients at entry using Johns Hopkins criteria. MP-MRI findings were assessed, including number of lesions, dominant lesion diameter, total lesion volume, prostate volume, and lesion density (calculated as total lesion volume/prostate volume). Lesions were assigned a suspicion score for cancer by MRI. AS criteria were reapplied based on the confirmatory biopsy, and accuracy of MP-MRI in predicting AS candidacy was assessed. Logistic regression modeling and chi-square statistics were used to assess associations between MP-MRI interpretation and biopsy results. Eighty-five patients qualified for AS with a mean age of 60.2 years and mean prostate-specific antigen level of 4.8 ng/mL. Of these, 25 patients (29%) were reclassified as not meeting AS criteria based on confirmatory biopsy. Number of lesions, lesion density, and highest MRI lesion suspicion were significantly associated with confirmatory biopsy AS reclassification. These MRI-based factors were combined to create a nomogram that generates a probability for confirmed AS candidacy. As clinicians counsel patients with PCa, MP-MRI may contribute to the decision-making process when considering AS. Three MRI-based factors (number of lesions, lesion suspicion, and lesion density) were associated with confirmatory biopsy outcome and reclassification. A nomogram using these factors has promising predictive accuracy for which future validation is necessary. Cancer 2013;119:3359-66. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.