Clinically-significant Cancer Research Articles

Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up

BackgroundThe initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis. ObjectiveTo determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not. Design, setting, and participantsThis is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling. Outcome measurements and statistical analysisPatients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2. Results and limitationsIn total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p = 0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p = 0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p = 0.019). ConclusionsBaseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates. Patient summaryThe ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance.This study is registered at ClinicalTrials.gov (NCT01354171).

In-Bore MRI-guided Prostate Biopsies: Retrospective Observational Study of Complementary Nontargeted Sampling of Normal-appearing Areas at Multiparametric MRI.

To investigate the pathologic outcomes of additional random biopsies from areas with no visible MR targets in the setting of targeted in-bore MRI-guided biopsy and to assess the negative predictive value (NPV) of areas with no visible MR targets stratified according to patients' different biopsy statuses. A retrospective analysis of patients who underwent in-bore MRI-guided biopsy with additional random biopsies in areas with no visible MR targets (Prostate Imaging-Reporting and Data System, version 2 category 1 or 2) was conducted in this study. Diagnostic scans and in-bore MRI-guided biopsy were performed with a 3-T MRI scanner. Areas with no visible MR targets were biopsied in a random fashion whenever a zone or side did not have a visible focal target. Clinically significant cancers (CSCs) were defined as a Gleason score of 7 or greater. NPVs were stratified based on patient's prior biopsy status. Descriptive analysis was performed. A total of 59 consecutive patients were included, with a median age of 65 years (interquartile range [IQR], 59-71 years). The median prostate-specific antigen level was 7 ng/mL (IQR, 4.9-10.8 ng/mL). Of the 59 patients, 16 (27.1%) were biopsy naive, 24 (40.7%) had prior negative transrectal US-guided biopsy findings, and 19 (32.2%) had prior positive transrectal US-guided biopsy findings. Forty-two (71.2%) biopsies revealed prostate cancer. A total of 112 areas with no visible MR targets were biopsied, of which 20 (17.9%) were cancers and 11 (9.8%) were CSCs. The NPV of areas with no visible MR targets was approximately 78% for all cancers and was 88.1% for CSCs. NPVs in biopsy-naive patients, patients with prior negative transrectal US-guided biopsy findings, and patients with prior positive transrectal US-guided biopsy findings were 62.5%, 83.3%, and 84.2%, respectively, for all cancers and 75.0%, 91.7%, and 94.7%, respectively, for CSCs. Areas with no visible MR targets in patients with MR-suspicious foci may still harbor CSCs that may significantly affect management plans. Additional biopsies from areas with no visible MR targets are warranted in this population.Keywords: Biopsy/Needle Aspiration, Interventional-Body, MR-Imaging, Prostate, Urinary© RSNA, 2019.

Evaluation of MSKCC Preprostatectomy nomogram in men who undergo MRI-targeted prostate biopsy prior to radical prostatectomy

IntroductionThe Memorial Sloan Kettering Cancer Center (MSKCC) Preprostatectomy nomogram is a widely used resource that integrates clinical factors to predict the likelihood of adverse pathology at radical prostatectomy. Adoption of magnetic resonance imaging targeted biopsy (TB) permits optimized detection of clinically-significant cancer over systematic biopsy (SB) alone. We aim to evaluate the prognostic utility of the MSKCC Preprostatectomy nomogram with TB pathology results. MethodsMen who underwent SB and magnetic resonance imaging TB who later underwent radical prostatectomy at our institution were included. Patient information was entered into the MSKCC Preprostatectomy nomogram using 5 biopsy reporting schemes with TB reported by both individual core (IC) and aggregate group (AG) methods. The likelihood of extraprostatic extension, seminal vesicle invasion, and lymph node involvement as predicted by the nomogram for each biopsy reporting schema were compared to radical prostatectomy pathology. ResultsWe identified 63 men from January 2014 to November 2017. On receiver operating characteristic analysis, IC-TB, AG-TB, SB plus IC-TB, and SB plus AG-TB exhibited similar, if not improved, area under the curve compared to SB alone in predicting extraprostatic extension (0.671, 0.674, 0.658, and 0.6613 vs. 0.6085). This was similarly observed for seminal vesicle invasion prediction using SB plus IC-TB compared to SB alone (0.727 vs. 0.733). For lymph node involvement, superior but nonsignificant area under the curve was observed for AG-TB (0.647) compared to IC-TB (0.571) and SB alone (0.524) ConclusionsUsing TB pathology results either alone or combined with SB pathology results as input to the MSKCC Preprostatectomy nomogram appears comparable for prognosticating adverse pathology on radical prostatectomy compared to SB alone, but robust validation is warranted prior to adoption into clinical practice.

Financial implications of biparametric prostate MRI.

Multiparametric magnetic resonance imaging (MP-MRI) targeted biopsy has been shown to identify more clinically-significant cancers and reduce the detection of clinically-insignificant disease when compared to systematic biopsy; however, the wide-spread accessibility of MP-MRI is limited. A potential strategy for reducing the cost, study time, and contrast-associated risks associated with MP-MRI is elimination of the dynamic contrast-enhanced (DCE) sequence, relying instead on biparametric MRI (BP-MRI). BP-MRI has been shown to have a diagnostic accuracy and cancer detection rate that are equivalent to those of MP-MRI. We modeled the potential cost of BP-MRI compared to MP-MRI to determine what cost savings would occur if DCE was eliminated from these studies. When controlled for a 45 min time window that allows for one full MP-MRI or three full BP-MRI studies, the BP-MRI 45 min gross profit is $1531.32. This is an increase in gross profit of $892.58 for the 45 min time window or $10,710.98 in a 9-h business day when performing BP-MRI compared to MP-MRI for prostate cancer detection. BP-MRI has the potential to result in substantial cost benefit and increased access to MRI in the diagnostic workflow and risk-stratification of men being evaluated for prostate cancer when compared to conventional MP-MRI.

Applying the PRECISION approach in biopsy naïve and previously negative prostate biopsy patients

ObjectivesThe PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal [1]. This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy. Methods and MaterialsClinical, imaging, and pathology data were prospectively collected from 358 biopsy naïve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ≥ 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2–5) and non-CSC (Grade Group 1). ResultsIn biopsy naïve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy. ConclusionsOur results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy naïve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI.

Validation of MSKCC pre-prostatectomy nomogram in men who undergo MRI-targeted prostate biopsy prior to radical prostatectomy.

14 Background: The Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Prostatectomy nomogram is a widely used resource using clinical factors to predict the likelihood of adverse pathology at radical prostatectomy. The increasing adoption of magnetic resonance imaging (MRI) and MRI-targeted biopsy (TB) permits optimized detection of clinically-significant cancer over systematic biopsy sampling alone. We aim to validate the prognostic utility of the MSKCC Pre-Prostatectomy nomogram with TB pathology results. Methods: Men who underwent systematic extended-sextant prostate biopsy (SB) followed by MRI TB who later underwent radical prostatectomy at our institution were included. Patient information was entered into the MSKCC Pre-Prostatectomy nomogram using five biopsy reporting schemes (SB alone, TB alone reported each of two ways (individual core (IC) technique or aggregate cores (AG) technique combining cores from a single MRI targeted lesion), and SB with TB combined with TB reported by both IC and AG methods. The likelihood of extracapsular extension (EPE), lymph node involvement (LNI), and seminal vesicle invasion (SVI) as predicted by the nomogram for each biopsy reporting schema were compared to radical prostatectomy pathology. Results: We identified 63 men from January 2014 to November 2017. On ROC analysis, IC-TB, AG-TB, SB plus IC-TB, and SB plus AG-TB exhibited similar, if not improved, AUC compared to SB alone in predicting EPE (0.671, 0.674, 0.658, and 0.6613 versus 0.6085). For LNI, superior AUC was observed for AG-TB (0.647) compared to IC-TB (0.571) and SB alone (0.524) Equivocal SVI prediction was observed for SB plus IC-TB compared to SB alone (0.727 versus 0.733). Conclusions: Using TB pathology results either alone or combined with SB pathology results for the MSKCC Pre-Prostatectomy nomogram appears comparable, if not improved, in prognosticating adverse pathologic features on radical prostatectomy compared to using SB core data alone from which the nomogram was developed.

Prebiopsy Biparametric MRI for Clinically Significant Prostate Cancer Detection With PI-RADS Version 2: A Multicenter Study.

The purpose of this study was to evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) with respect to prebiopsy MRI with and without dynamic contrast enhancement in the detection of clinically significant cancer (CSC). A total of 113 patients with prostate cancer who underwent radical prostatectomy and prebiopsy multiparametric 3-T MRI (mpMRI) that included T2-weighted imaging, DWI, and dynamic contrast-enhanced MRI (DCE-MRI) were enrolled in a retrospective study conducted at two institutions. For detecting CSC at prebiopsy mpMRI with DCE-MRI and biparametric MRI (bpMRI) without DCE-MRI, two independent radiologists using PI-RADSv2 scored suspicious lesions in all patients. CSC was identified in 74.3% (84/113) of patients. For CSC detection rate, no statistical differences between bpMRI and mpMRI were found for any PI-RADS score (p > 0.05). For cancer in the peripheral zone, reader 1 upgraded 22 lesions and reader 2 upgraded 13 lesions from PI-RADS score 3 at bpMRI to PI-RADS 4 (3 + 1) at mpMRI. The CSC detection rate of PI-RADS 3 + 1 lesions at mpMRI (reader 1, 63.6%; reader 2, 69.2%) was slightly greater than that of PI-RADS 3 lesions at bpMRI (reader 1, 53.8%; reader 2, 60.0%), which was not statistically different (p > 0.05). Interreader agreement on PI-RADS scoring was moderate for both bpMRI (κ = 0.540) and mpMRI (κ = 0.478). For detecting CSC, the diagnostic performance of prebiopsy bpMRI without DCE-MRI is similar to that of mpMRI with DCE-MRI.

The clinical utility of transperineal template-guided saturation prostate biopsy for risk stratification after transrectal ultrasound-guided biopsy.

PurposeTo investigate the clinical utility of transperineal template-guided saturation prostate biopsy (TPB) for risk stratification after transrectal ultrasound (TRUS)-guided biopsy.Materials and MethodsWe retrospectively reviewed 155 patients who underwent TPB after previously negative results on TRUS-guided biopsy (n=58) or who were candidates for active surveillance (n=97) fulfilling the PRIAS criteria between May 2017 and November 2018. The patients' clinicopathologic data were reviewed, and the detection of clinically significant cancer (CSC) and upgrading of Gleason grade were identified.ResultsThe patients' median age and pre-TPB prostate-specific antigen (PSA) value were 65.0 years and 5.74 ng/mL, respectively. A median of 36 biopsy cores was obtained in each patient, with a median TPB core density of 0.88 cores/cm3. Of the 58 males with a previous negative result on TRUS-guided biopsy, prostate cancer (PCa) was detected in 17 males (29.3%), including 8 with CSC. Of the 97 patient candidates for active surveillance, upgrading of the Gleason grade was identified in 31 males (32.0%), 20 with a Gleason grade of 7 (3+4), 6 with a Gleason grade of 7 (4+3), and 5 with a Gleason grade of 8 (4+4). The overall complication rate was 14.8% (23/155), and there were no Clavien–Dindo grade 3 to 5 complications.ConclusionsTPB helps to stratify the risk of PCa that was previously missed or underdiagnosed by TRUS-guided biopsy. TPB might be used as a diagnostic tool to determine risk classification and to help counsel patients with regard to treatment decisions.

ARFI and shear wave imaging of the prostate to delineate clinically-significant cancers

Current prostate cancer screening methods involve non-targeted needle biopsies and the detection of clinically-insignificant lesions that receive excessive treatments, exposing patients to unnecessary adverse side effects and placing a burden on our health care systems. There is a strong clinical need for improved prostate imaging methods that are sensitive and specific for clinically-significant prostate cancer lesions to guide needle biopsies, target focal treatments, and improve overall patient outcomes. We have developed a 3D, in vivo Acoustic Radiation Force Impulse (ARFI) imaging and Shear Wave Elasticity Imaging (SWEI) system using a side-fire endorectal linear array with a custom rotation stage to collect prostate imaging volumes to identify regions of suspicion that should be targeted during biopsy procedures. We have validated that ARFI imaging can reliability identify regions of clinically-significant prostate cancer by comparing our imaging volumes with whole-mount histology in patients undergoing radical prostatectomy; however, there was opportunity to improve the diagnostic sensitivity and specificity by combining ARFI imaging data with SWEI. While ARFI images contain regions of relative contrast (decreased displacement) to delineate regions of suspicion, we hypothesized that SWEI could provide absolute shear wave speeds that could quantify the degree of suspicion of an identified lesion, with more aggressive lesions being stiffer and having higher shear wave speeds. In an ongoing clinical study of over 30 patients, we have demonstrated that the combination of ARFI and SWEI data can improve the diagnostic accuracy of clinically-significant lesion identification, while the inclusion of B-mode echogenicity was not found to improve diagnostic accuracy. More complex classification models to identify clinically-significant prostate cancer using ARFI and SWEI metrics are being developed using Linear Discriminant Analysis (LDA) and Support-Vector Machines (SVMs). These classification models will be further extended to explore the diagnostic value of additional quantitative ultrasound metrics derived from the raw radiofrequency (RF) data and other imaging methods commonly used in the diagnostic workup of prostate cancer patients, such as multiparametric magnetic resonance imaging (mp-MRI).

Reduced Core Targeted (RCT) biopsy: Combining multiparametric magnetic resonance imaging - transrectal ultrasound fusion targeted biopsy with laterally-directed sextant biopsies – An alternative template for prostate fusion biopsy

Purpose: To introduce and assess the efficacy of a Reduced Core Targeted (RCT) biopsy template (image-targeted + laterally directed sextant biopsy) to detect clinically-significant cancer in patients with elevated PSA and a previous negative biopsy or on active surveillance. The performance and added value of either targeted alone vs random sextant vs combined biopsy template was appraised.Methods: Data from 113 patients with a suspicious lesion on mpMRI and previous history of extended 10–12 core standard biopsy who subsequently had a RCT-biopsy were analyzed. These patients had at least one prior negative standard 10–12 core biopsy (n = 70) or were on active surveillance (n = 43). At least two samples were taken from each mpMRI lesion as a targeted biopsy together with the classic laterally-directed sextant biopsy.Results: In patients having previous negative biopsy (n = 70), the RCT biopsy detected any cancer versus clinically-significant cancer in 62.9% versus 32.9%, respectively. Targeted biopsy diagnosed more clinically-significant cancers than sextant biopsy (31.4% versus 25.7%, p < 0.01). In this cohort, the use of targeted fusion biopsy upgraded the biopsy grade group (GrGp) in 15 (21.4%) patients compared to sextant biopsy. In patients on active surveillance, the RCT biopsy identified any cancer versus clinically-significant cancer for detection rates of 74.4% versus 39.5%, respectively. Fusion targeted biopsy diagnosed more clinically-significant cancers than sextant biopsy did (37.2% versus 18.6%, p = 0.002). The use of targeted biopsy upgraded the biopsy GrGp in 12 (27.9%) patients.Conclusion: As a preliminary study, among men with MRI suspicious lesions and previous negative prostate biopsy or those under active surveillance, an image-targeted plus sextant biopsy platform can be associated with increased efficiency of detecting clinically-significant prostate cancer with fewer random cores. Future large series are needed to validate the clinical implication of this reduced core template in comparison with targeted fusion biopsy plus standard 12-core schema.

MRI findings guiding selection of active surveillance for prostate cancer: a review of emerging evidence.

Active surveillance (AS) for prostate cancer (PCa) is generally considered to be a safe strategy for men with low-risk, localized disease. However, as many as 1 in 4 patients may be incorrectly classified as AS-eligible using traditional inclusion criteria. The use of multiparametric magnetic resonance imaging (mpMRI) may offer improved risk stratification in both the initial diagnostic and disease monitoring setting. We performed a review of recently published studies to evaluate the utility of this imaging modality for this clinical setting. An English literature search was conducted on PubMed for original investigations on localized PCa, AS, and magnetic resonance imaging. Our Boolean criteria included the following terms: PCa, AS, imaging, MRI, mpMRI, prospective, retrospective, and comparative. Our search excluded publication types such as comments, editorials, guidelines, reviews, or interviews. Our literature review identified 71 original investigations. Among these, 52 met our inclusion criteria. Evidence suggests mpMRI improves characterization of clinically significant prostate cancer (csPCa) foci, and the enhanced detection and risk-stratification afforded by this modality may keep men from being inappropriately placed on AS. Use of serial mpMRI may also permit longer intervals between confirmatory biopsies. Multiple studies demonstrate the benefit of MRI-targeted biopsies. The use of mpMRI of the prostate offers improved confidence in risk-stratification for men with clinically low-risk PCa considering AS. While on AS, serial mpMRI and MRI-targeted biopsy aid in the detection of aggressive disease transformation or foci of clinically-significant cancer undetected on prior biopsy sessions.

The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort.

Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort. The study-population consisted of 533 men in ages 45-75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP). 263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7-89.2) and AUC 74.8 (95% CI 70.3-79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer. A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

Pre-biopsy MRI as an adjunct for cancer detection in men with elevated PSA and no previous biopsy.

The role of magnetic resonance imaging (MRI) prior to biopsy in the diagnosis of prostate cancer in biopsy-naïve patients has been strengthened by recent developments such as the PIRADS V2 criteria, which cover acquisition, interpretation, and reporting for clinical practice and data collection for research. Important questions on the role of prostate MRI remain: can MRI be used as a triage test before first biopsy series? Can it be used to avoid the use of systematic biopsies (SB) and instead use only targeted biopsies (TB) to MRI-suspicious lesions? Studies to evaluate image guided TB compared to SB have started to accumulate. Objectives of these studies should be to reduce the detection of clinically insignificant disease, to maximize the detection of clinically significant cancer (CSC), to better assess disease size, grade and location. Accurate diagnosis will allow the choice of the most appropriate treatments options, minimising side effects and reducing overtreatment. Study results on MRI-TB detection rates are promising however some limitations should be considered. The majority of published and ongoing studies have been performed at expert centres, in order to demonstrate the optimal performance of MRI. Then, the validation of this strategy in less specialised institutions will be necessary before incorporating recommendations in international guidelines. It necessitates training for radiologists and urologists to perform and read MRI and MRI-targeted biopsy through education programs and standardization tools. All these advances will be consolidated with expected genetic screening tools to improve the detection of aggressive cancer.

PI-RADSv2: How we do it.

5 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:11-23.

The necessity of dynamic contrast enhanced imaging for prostate MRI: A study of pathologic outcomes on prostate biopsy.

52 Background: PIRADS version 2 guidelines for the interpretation of multi-parametric prostate MRI (mpMRI) stipulates that dynamic contrast-enhanced (DCE) imaging be used to classify diffusion weighted imaging (DWI) score 3 peripheral zone lesions into PIRADS-3 (DCE-) or PIRADS-4 (DCE+) lesions. Despite this, it is unknown if DCE based classification separates lesions into clinically meaningful pathologic groups. Because use of contrast adds time, risk (though modest), and cost to mpMRI, we sought to examine whether use of DCE indeed improves detection of clinically-significant cancer. Methods: Using the Johns Hopkins MRI-ultrasound fusion prostate biopsy database and including only patients without a prior diagnosis of prostate cancer (n = 232), we identified patients with peripheral zone DWI-3 or DWI-4 lesions who underwent targeted biopsy of those lesions. Each lesion meeting the MRI criteria was considered separately, and grouped into one of three lesion MRI classifications – DWI-3/DCE-/PIRADS-3, DWI-3/DCE+/PIRADS-4, or DWI-4/PIRADS-4. The rates of benign, grade group (GG) 1, and GG ≥ 2 pathology were compared between the MRI classification groups. Results: One hundred forty-eight peripheral zone DWI-3 or DWI-4 lesions from a total of 106 patients were identified. The rate of benign(%)/GG1(%)/GG ≥ 2(%) biopsy pathology in the groups DWI-3/DCE-/PIRADS-3 (61 lesions), DWI-3/DCE+/PIRADS-4 (37 lesion), and DWI-4/PIRADS-4 (47 lesions) was 68.9/18.0/8.2, 59.5/13.5/18.9, and 44.7/23.4/27.7, respectively (P &gt; 0.05 for the difference in rates of GG ≥ 2 pathology between the two PIRADS-4 groups and the two DWI-3 groups). Conclusions: Given the cost and morbidity of using intravenous contrast agents in prostate MRI, their clinical utility must be determined. In this study, DWI-3 peripheral zone lesions with DCE positivity appear to have a higher rate of clinically-significant (GG ≥ 2) cancer on biopsy. This study supports the use of DCE to better classify DWI-3 peripheral zone lesions however further study with expanded cohorts is indicated.

MR/US Image-Fusion Targeted Biopsy for Diagnosis of Clinically Significant Prostate Cancer

Recent reports suggest the multi-parametric magnetic-resonance image (MRI) for prostate have high accuracy to visualize the clinically significant cancer (CSCa). The utility of MR/US image-fusion targeted biopsy (MRUS-TB) has been reported using computer-software assisted elastic image-fusion system (Koelis). The aim of this study is to report our experience of MRUS-TB for diagnosis of prostate cancer. A retrospective review of total 262 consecutive patients with age of 69 y.o. (37-88), and PSA of 7.1ng/ml (4.0-19.8), who had pre-biopsy MRI with suspicious lesion for CSCa and underwent combination of systematic biopsy (SBx) (6 cores) and MRUS-TB (2 cores). Positive rate of any cancer, positive rate of CSCa, Gleason score (GS), and maximum cancer core length (MCCL) were compared between SBx versus MRUS-TB. The CSCa was defined as GS6 cancer with MCCL≧5mm or any cancer with GS≧7. Overall, the positive rate of any cancer per patients was 61% (160/262) in SBx vs. 79% (207/262) in MRUS-TB (p<0.0001); and that of CSCa per patients was 46% (120/262) in SBx vs. 70% (181/262) in MRUS-TB (p<0.0001). Positive rate of any cancer per core was 21.7% (330/1523) in SBx vs. 68.6% (406/592) in MRUS-TB (p<0.0001), and that of CSCa per core was 12.7% (193/1423) in SBx vs. 60.3% (357/592) in MRUS-TB (p<0.0001). Distribution of Gleason score (6/7/8/9/10) was 59/71/23/6/1 in SBx vs. 48/105/36/15/2 (p=0.005). MCCL was 5mm (0.5-16) in SBx vs. 8mm (1-19mm) in MRUS-TB (p<0.0001). MRUS-TB was associated with higher detection rate of CSCa than SBx.

Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients

BackgroundUp to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. ObjectiveTo evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. Design, setting, and participantsThe French Urological Association initiated a prospective IDEAL multi-institutional study (2009–2015), to evaluate HIFU-hemiablation as a primary treatment. InterventionMultiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. Outcome measurements and statistical analysisPrimary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. Results and limitationsOne hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. ConclusionsAt 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. Patient summaryThis report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.

A nomogram for prediction of prostate cancer on multi‐core biopsy using age, serum prostate‐specific antigen, prostate volume and digital rectal examination in Singapore

To develop and internally validate two nomograms for predicting the probability of overall and clinically-significant prostate cancer on initial biopsy in a Singaporean population. Data were collected from men undergoing initial prostate biopsy at a single center. The indications for biopsy were serum prostate-specific antigen (PSA) ≥4.0 ng/mL or suspicious digital rectal examination (DRE) findings. Men with PSA >30 ng/mL were excluded. Age, PSA, prostate volume (PV) and DRE were predictors included in our logistic regression model and used to construct two nomograms for overall prostate cancer and clinically-significant (Gleason sum ≥7) cancer detection. Predictive accuracies of our nomograms were assessed using area under curve (AUC) of their receiver-operator characteristic curves. Internal validation was performed using the bootstrap method. Our nomograms were compared to a model based on PSA alone using AUC and decision curve analysis (DCA). Out of 672 men analyzed, our positive biopsy rate was 26.2% (n = 176), of which 63.6% (n = 112) had clinically significant disease. Age, PSA, PV and DRE status were all independent risk factors for both overall prostate cancer detection as well as clinically-significant cancer detection (all P < 0.05). Our nomogram outperformed serum PSA for both overall and clinically-significant cancer detection (0.736 vs 0.642, P < 0.001 and 0.793 vs 0.696, P < 0.001, respectively). Using DCA, our nomograms had superior net benefit and net reduction in biopsy rate compared to PSA alone. Our nomograms have been shown to be superior to PSA alone, on both AUC and DCA. However, it warrants external validation.

MP16-16 GLEASON SCORING OF PROSTATE BIOPSIES IN ACTIVE SURVEILLANCE PATIENTS OBTAINED BY STANDARD TRUS AND MRI: AN UPDATE

INTRODUCTION AND OBJECTIVES: MRI-TRUS biopsy systems allow MRI to be linked to the practicality of ultrasound and may be useful in the selection and follow up of active surveillance (AS) patients. Our previously reported experience contradicted most series in which MRI-TRUS significantly increases the detection rate of clinically-significant cancers. In this follow up study, we examined whether process changes and increased experience resulted in increased MRI-TRUS detection of significant cancer. METHODS: Two cohorts were identified (i) a training group of 75 AS patients (Jan-Dec 2014), and (ii) a study group of 65 AS patients (Dec 2014-Sept 2015). MRI-TRUS process changes (software upgrade, improvements in image alignment, and prevention of RF interference) were implemented. An MRI-TRUS (3T or 1.5T with endorectal coil) confirmatory biopsy was performed within 1 year in AS patients. Regions of interest (ROI) were identified. 12 systematic standard TRUS biopsies and 3 cores from each ROI using MRI-TRUS fusion (UroNav) were performed. Gleason score 7 or a single core volume of >50% was considered clinically significant. Each patient served as their own control. Rates of clinically significant cancer detected by standard biopsies, ROI biopsies, and both methodologies were determined. RESULTS: In the training and study groups, 36.0% (27/75) and 33.8% (22/65) of patients, respectively had clinically significant cancer. In the training group, 11.1% (3/27) were identified by MRI-TRUS fusion alone, 51.9% (14/27) by standard TRUS alone, and 37.0% (10/27) by both biopsy methods. In the study group, 13.6% (3/22) were identified by MRI-TRUS fusion alone, 50.0% (11/22) by standard TRUS alone, and 36.4% (8/22) were by both biopsy methods. CONCLUSIONS: Despite process improvements and increased experience, MRI-TRUS fusion only increased the rate of detecting clinically significant cancer to 13.6%. Importantly, performing MRI-TRUS fusion alone and eliminating standard systematic biopsies would have missed 51% of clinically significant cancers. Our continued experience with MRI-TRUS fusion continues to contradict most published series in which MRI-TRUS fusion significantly increases the detection rate of clinically significant cancers.