Boris Hadaschik

Standards of Reporting for MRI-targeted Biopsy Studies (START) of the Prostate: Recommendations from an International Working Group.

BACKGROUND A systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies. OBJECTIVE To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING, AND PARTICIPANTS Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist). RESULTS AND LIMITATIONS The strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies. CONCLUSIONS Use of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

A Novel Stereotactic Prostate Biopsy System Integrating Pre-Interventional Magnetic Resonance Imaging and Live Ultrasound Fusion

PURPOSE We developed an effective way to precisely diagnose prostate cancer using a novel prostate biopsy system that integrates pre-interventional magnetic resonance imaging with peri-interventional ultrasound for perineal navigated prostate biopsy. MATERIALS AND METHODS A total of 106 men with findings suspicious for prostate cancer (median age 66 years, prostate specific antigen 8.0 ng/ml and prostate volume 47 ml) underwent multiparametric 3 Tesla magnetic resonance imaging. Suspicious lesions were marked and data were transferred to the novel biopsy system. Using a custom-made biplane transrectal ultrasound probe mounted on a stepper we gathered 3-dimensional ultrasound data and fused them with magnetic resonance imaging data. As a result, suspicious magnetic resonance imaging lesions were superimposed over the transrectal ultrasound data. Three-dimensional biopsy planning was done, including systematic biopsies. Perineal biopsies were taken under live ultrasound guidance and the precise site of each biopsy was documented in 3 dimensions. We evaluated feasibility, safety and cancer detection. RESULTS Prostate cancer was detected in 63 of 106 patients (59.4%). Magnetic resonance imaging findings correlated positively with histopathology in 71 of 103 patients (68.9%). In magnetic resonance imaging lesions marked as highly suspicious, the detection rate was 95.8% (23 of 24 cases). Lesion targeted cores had a significantly higher positivity rate than nontargeted cores. The procedural targeting error of the first 2,461 biopsy cores was 1.7 mm. Regarding adverse effects, 2 patients experienced urinary retention and 1 had a perineal hematoma. Urinary tract infections did not develop. CONCLUSIONS Perineal stereotactic prostate biopsies guided by the combination of magnetic resonance imaging and ultrasound enable effective examination of suspicious magnetic resonance imaging lesions. Each biopsy core taken is documented accurately for its location in 3 dimensions, enabling magnetic resonance imaging validation and tailored treatment planning. The morbidity of the procedure was minimal.

Critical Evaluation of Magnetic Resonance Imaging Targeted, Transrectal Ultrasound Guided Transperineal Fusion Biopsy for Detection of Prostate Cancer

PURPOSE Diagnosis and precise risk stratification of prostate cancer is essential for individualized treatment decisions. Magnetic resonance imaging/transrectal ultrasound fusion has shown encouraging results for detecting clinically significant prostate cancer. We critically evaluated magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy in routine clinical practice. MATERIALS AND METHODS Included in this prospective study were 347 consecutive patients with findings suspicious for prostate cancer. Median age was 65 years (range 42 to 84) and mean prostate specific antigen was 9.85 ng/ml (range 0.5 to 104). Of the men 49% previously underwent transrectal ultrasound guided biopsies, which were negative, and 51% underwent primary biopsy. In all patients 3 Tesla multiparametric magnetic resonance imaging was done. Systematic stereotactic prostate biopsies plus magnetic resonance imaging targeted, transrectal ultrasound guided biopsies were performed in those with abnormalities on magnetic resonance imaging. Imaging data and biopsy results were analyzed. A self-designed questionnaire was sent to all men on further clinical history and biopsy adverse effects. RESULTS Of 347 patients biopsy samples of 200 (58%) showed prostate cancer and 73.5% of biopsy proven prostate cancer were clinically relevant according to National Comprehensive Cancer Network (NCCN) criteria. On multiparametric magnetic resonance imaging 104 men had findings highly suspicious for prostate cancer. The tumor detection rate was 82.6% (86 of 104 men) with a Gleason score of 7 or greater in 72%. Overall targeted cores detected significantly more cancer than systematic biopsies (30% vs 8.2%). Of 94 patients without cancer suspicious lesions on magnetic resonance imaging 11 (11.7%) were diagnosed with intermediate risk disease. Regarding adverse effects, 152 of 300 patients (50.6%) reported mild hematuria, 26% had temporary erectile dysfunction and 2.6% needed short-term catheterization after biopsy. Nonseptic febrile urinary tract infections developed in 3 patients (1%). CONCLUSIONS Magnetic resonance imaging targeted, transrectal ultrasound guided transperineal fusion biopsy provides high detection of clinically significant tumors. Since multiparametric magnetic resonance imaging still has some limitations, systematic biopsies should currently not be omitted. The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting.

Comparative Analysis of Transperineal Template Saturation Prostate Biopsy Versus Magnetic Resonance Imaging Targeted Biopsy with Magnetic Resonance Imaging-Ultrasound Fusion Guidance

PURPOSE Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinically significant prostate cancer. However, standardized prospective evaluation is limited. MATERIALS AND METHODS A total of 294 consecutive men with suspicion of prostate cancer (186 primary, 108 repeat biopsies) enrolled in 2013 underwent 3T multiparametric magnetic resonance imaging (T2-weighted, diffusion weighted, dynamic contrast enhanced) without endorectal coil and systematic transperineal cores (median 24) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration (median 4). The highest Gleason score from each biopsy method was compared. McNemars tests were used to evaluate detection rates. Predictors of Gleason score 7 or greater disease were assessed using logistic regression. RESULTS Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed. Systematic, transperineal biopsy missed 18 Gleason score 7 or greater tumors (20.9%) while targeted biopsy did not detect 11 (12.8%). Targeted biopsy of PI-RADS 2-5 alone overlooked 43.8% of Gleason score 6 tumors. McNemars tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies (p=0.08). Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0% of targeted biopsy vs 7.5% of systematic, transperineal biopsy cores detecting Gleason score 7 or greater cancers. To diagnose 1 Gleason score 7 or greater cancer, 3.4 targeted and 7.4 systematic biopsies were needed. Limiting biopsy to men with PI-RADS 3-5 would have missed 17 Gleason score 7 or greater tumors (19.8%), demonstrating limited magnetic resonance imaging sensitivity. PI-RADS scores, digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease. CONCLUSIONS Compared to systematic, transperineal biopsy as a reference test, magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 or greater tumors while simultaneously mitigating the detection of lower grade disease. The gold standard for cancer detection in primary biopsy is a combination of systematic and targeted cores.

Multiparametric Magnetic Resonance Imaging (MRI) and MRI–Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen

BACKGROUND Multiparametric magnetic resonance imaging (mpMRI) and MRI fusion targeted biopsy (FTB) detect significant prostate cancer (sPCa) more accurately than conventional biopsies alone. OBJECTIVE To evaluate the detection accuracy of mpMRI and FTB on radical prostatectomy (RP) specimen. DESIGN, SETTING AND PARTICIPANTS From a cohort of 755 men who underwent transperineal MRI and transrectal ultrasound fusion biopsy under general anesthesia between 2012 and 2014, we retrospectively analyzed 120 consecutive patients who had subsequent RP. All received saturation biopsy (SB) in addition to FTB of lesions with Prostate Imaging Reporting and Data System (PI-RADS) score ≥2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The index lesion was defined as the lesion with extraprostatic extension, the highest Gleason score (GS), or the largest tumor volume (TV) if GS were the same, in order of priority. GS 3+3 and TV ≥1.3ml or GS ≥3+4 and TV ≥0.55ml were considered sPCa. We assessed the detection accuracy by mpMRI and different biopsy approaches and analyzed lesion agreement between mpMRI and RP specimen. RESULTS AND LIMITATIONS Overall, 120 index and 71 nonindex lesions were detected. Overall, 107 (89%) index and 51 (72%) nonindex lesions harbored sPCa. MpMRI detected 110 of 120 (92%) index lesions, FTB (two cores per lesion) alone diagnosed 96 of 120 (80%) index lesions, and SB alone diagnosed 110 of 120 (92%) index lesions. Combined SB and FTB detected 115 of 120 (96%) index foci. FTB performed significantly less accurately compared with mpMRI (p=0.02) and the combination for index lesion detection (p=0.002). Combined FTB and SB detected 97% of all sPCa lesions and was superior to mpMRI (85%), FTB (79%), and SB (88%) alone (p<0.001 each). Spearmans rank correlation coefficient for index lesion agreement between mpMRI and RP was 0.87 (p<0.001). Limitations included the retrospective design, multiple operators, and nonblinding of radiologists. CONCLUSIONS MpMRI identified 92% of index lesions compared with RP histopathology. The combination of FTB and SB was superior to both approaches alone, reliably detecting 97% of sPCa lesions. PATIENT SUMMARY Multiparametric magnetic resonance imaging detects the index lesion accurately in 9 of 10 patients; however, the combined biopsy approach, while missing less significant cancer, comes at the cost of detecting more insignificant cancer.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography–guided biopsy for prostate‐cancer detection in men with a raised prostate‐specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography–guided biopsy. Men in the MRI‐targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10‐to‐12–core, transrectal ultrasonography–guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI‐targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI‐targeted biopsy group, as compared with 64 of 248 (26%) in the standard‐biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI‐targeted biopsy group than in the standard‐biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, ‐13 percentage points; 95% CI, ‐19 to ‐7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI‐targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027.)

Clusterin facilitates COMMD1 and I-κB degradation to enhance NF-κB activity in prostate cancer cells

Secretory clusterin (sCLU) is a stress-activated, cytoprotective chaperone that confers broad-spectrum cancer treatment resistance, and its targeted inhibitor (OGX-011) is currently in phase II trials for prostate, lung, and breast cancer. However, the molecular mechanisms by which sCLU inhibits treatment-induced apoptosis in prostate cancer remain incompletely defined. We report that sCLU increases NF-κB nuclear translocation and transcriptional activity by serving as a ubiquitin-binding protein that enhances COMMD1 and I-κB proteasomal degradation by interacting with members of the SCF-βTrCP E3 ligase family. Knockdown of sCLU in prostate cancer cells stabilizes COMMD1 and I-κB, thereby sequestrating NF-κB in the cytoplasm and decreasing NF-κB transcriptional activity. Comparative microarray profiling of sCLU-overexpressing and sCLU-knockdown prostate cancer cells confirmed that the expression of many NF-κB–regulated genes positively correlates with sCLU levels. We propose that elevated levels of sCLU promote prostate cancer cell survival by facilitating degradation of COMMD1 and I-κB, thereby activating the canonical NF-κB pathway. Mol Cancer Res; 8(1); 119–30

Application technique: placement of a prostate-rectum spacer in men undergoing prostate radiation therapy.

Study Type – Therapy (case series)

Histology core‐specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate

To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single‐core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI.