Office-based Magnetic Resonance Imaging-guided Transperineal Prostate Biopsy Without Antibiotic Prophylaxis: A Real-world Clinical Utility Study.

Background and objective: Advances in for magnetic resonance imaging (MRI)-guided transperineal biopsy (TPBx) techniques have facilitated outpatient prostate biopsies under local anaesthesia to lower postbiopsy infection rates. However, there is debate regarding antibiotic prophylaxis because of concerns regarding antibiotic resistance and interactions. Our objective was to assess the transition from office-based transrectal biopsy to TPBx performed under local anaesthesia without antibiotic prophylaxis despite potential risk factors for infectious complications. Methods: We conducted a prospective assessment of 665 men undergoing office-based MRI-guided TPBx. The primary outcome was the rate of urosepsis or febrile urinary tract infections requiring hospitalisation and/or antibiotics within 2 wk after biopsy. Secondary outcomes included patient-reported procedure tolerability and the prostate cancer detection rate. Key findings and limitations: TPBx using a median of nine cores per patient (range 4-15) detected prostate cancer in 534/665 men (80%). Only four men (0.6%) were hospitalised for suspected postbiopsy infection; no patient experienced urosepsis. The TPBx procedure was well tolerated, with low pain scores (median Visual Analogue Scale score of 2, interquartile range [IQR] 1-3) and positive patient ratings (median rating 1 [no problem], IQR 1-2). Limitations include the single-centre analysis and lack of randomisation for antibiotic prophylaxis. Conclusions and clinical implications: An office-based TPBx strategy under local anaesthesia without antibiotic prophylaxis is well tolerated and has a very low risk of side effects. This approach should be considered as the standard of care. Further studies may determine if a subgroup of predisposed men could benefit from antibiotic prophylaxis. Patient summary: For prostate biopsy the sampling needle can be inserted through the rectum or through the perineum, which is the skin between the rectum and the scrotum. Our study confirms that in everyday clinical practice, prostate biopsy via the perineum can be carried out under local anaesthetic and without routine use of antibiotics because of its lower risk of infection. Patients reported low pain scores and positive ratings for the overall experience.

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP.

INTRODUCTION: The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer. METHODS AND ANALYSIS: Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.We will measure the levels of the three microRNAs in the uCaP model (miR-222-3 p, miR-24-3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies. ETHICS AND DISSEMINATION: This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings. TRIAL REGISTRATION NUMBER: NCT05767307 at clinicaltrials.gov.

Quantification of cross-vendor variation in ADC measurements in vendor-specific prostate MRI-protocols.

PURPOSE: The purpose of this study was to quantify the variability of Apparent Diffusion Coefficient (ADC) and test if there were statistically significant differences in ADC between MRI systems and sequences. METHOD: With a two-chamber cylindrical ADC phantom with fixed ADC values (1,000 and 1,600x10-6 mm2/s) a single-shot (ss) Echo Planar Imaging (EPI), a multi-shot EPI, a reduced field of view DWI (zoom) and a Turbo Spin Echo DWI sequence were tested in six MRI systems from three vendors at 1.5 T and 3 T. Technical parameters were according to Prostate Imaging Reporting and Data System Version 2.1. ADC maps were calculated by vendor specific algorithms. Absolute and relative differences in ADC from the phantom-ADC were calculated and differences between sequences were tested. RESULTS: At 3 T absolute differences from phantom given ADC (∼1,000 and âˆ¼ 1,600x10-6 mm2/s) were -83 - 42x10-6 mm2/s (-8.3%-4.2%) and -48 - 15x10-6 mm2/s (-3%-0.9%), respectively and at 1.5 T absolute differences were -81 - 26x10-6 mm2/s (-2.6%-8.1%) and -74 - 67x10-6 mm2/s (-4.6%-4.2%), respectively. Significant statistical differences in ADC measurements were identified between vendors in all sequences except for ssEPI and zoom at 3 T in the 1,600x10-6 mm2/s phantom chamber. Significant differences were also identified between ADC measurements at 1.5 T and 3 T in some of the sequences and vendors, but not all. CONCLUSION: The variation of ADC between different MRI systems and prostate specific DWI sequences is limited in this phantom study and without apparent clinical relevance. However, prospective multicenter studies of prostate cancer patients are needed for further investigation.

Comparison of PSA density and lesion volume strategies for selecting men with equivocal PI-RADS 3 lesions on bpMRI for biopsies.

PURPOSE: To compare two strategies: Prostate-specific antigen density (PSAd) and lesion volume measurement in ruling out significant prostate cancer (sPCa) in men with equivocal Prostate Imaging Reporting and Data System (PI-RADS) category 3 index lesions on biparametric magnetic resonance imaging. METHODS: In total, 130 men from our database had index lesions with PI-RADS scores of 3. Prostate volume was measured using the ellipsoid method, in accordance with PI-RADS version 2.1 criteria. Index lesion volumes were also measured using the ellipsoidal formula on the diffusion-weighted imaging sequence with the highest b-value and sagittal T2 sequences. RESULTS: Among 130 men with PI-RADS category 3 index lesions, 23 (18%) had sPCa. In total, 6 of the 89 men with PSAd < 0.15 ng/mL2 (7%) had sPCa, whereas 8 of the 49 men with index lesion volumes < 0.5 mL (16%) had sPCa. The difference was statistically significant (McNemar, p < 0.0001). CONCLUSION: The PSAd strategy performed better than the lesion volume strategy in ruling out sPCa in men with equivocal PI-RADS category 3 index lesions.

Early experience in avoiding biopsies for biopsy-naïve men with clinical suspicion of prostate cancer but non-suspicious biparametric magnetic resonance imaging results and prostate-specific antigen density < 0.15 ng/mL2: A 2-year follow-up study.

Background: Only limited data have been published on the diagnostic accuracy of combining biparametric (bp) magnetic resonance imaging (MRI) and prostate-specific antigen density (PSAd) to rule out biopsies. Purpose: The purpose is to assess the 2-year risk of being diagnosed with sPCa following the strategy of avoiding immediate biopsies in men with non-suspicious bp MRIs and a PSAd <0.15 ng/mL2. Material and Methods: Two hundred biopsy-naïve men with clinical suspicion of PCa underwent a pre-biopsy bp MRI from March to July 2019. Of these, 109 men had a Prostate Imaging Reporting and Data System (PI-RADS) score of 1-3 including 77 men with calculated PSAd <0.15 ng/mL2. As a result, no biopsies were performed in these 77 men, who were clinically followed up for at least 2 years and re-examined in case of rising suspicion of sPCa. The remaining 32 men with a calculated PSAd ≥0.15 ng/mL2 underwent systematic biopsies and targeted biopsies of any PI-RADS 3 lesion. Results: One of the 77 men (1.3%) had an sPCa diagnosed within 2 years of follow-up. All men were referred back to their general practitioner within 1 year and 9% (7/77) were re-referred to the urology department during follow-up. Among these men, 43% (3/7) continued to have PSA levels that were above their individual thresholds at confirmatory testing and underwent secondary MRI scans. Conclusions: No biopsies for men with bpMRI results exhibiting maximum PI-RADS 3 and with a PSAd <0.15 ng/mL2 resulted in a 2-year risk of being diagnosed with sPCa of 1.3%.

Outcome of 5-year follow-up in men with negative findings on initial biparametric MRI.

BACKGROUND: We assessed the 5-year risk of being diagnosed with significant prostate cancer following a low-suspicion biparametric magnetic resonance imaging result. METHODS: The study population was derived from a prospective database used to assess the diagnostic accuracy of biparametric magnetic resonance imaging for significant prostate cancer detection in 1020 biopsy-naïve men. Significant prostate cancer was defined as any core with Gleason grade group ≥3 or a maximum cancerous core length greater than 50% of Gleason grade group 2. A secondary definition of significant prostate cancer was also included: any core with prostate cancer Gleason grade group ≥2. Of the 1020 men, 305 had a low-suspicion biparametric magnetic resonance imaging result (Prostate Imaging Reporting and Data System score of 1 or 2) but four men were excluded from follow-up. Thus, the final study population consisted of 301 men, who were clinically followed-up from inclusion (November 2015 to June 2017) until 1 June 2021. FINDINGS: Overall, 1·7% (5/301) of the study population had significant prostate cancer diagnosed within 5 years (median 1480 days, Interquartile Range (1587-1382)) of their low-suspicion result and corresponding set of biopsies. When the secondary definition of significant prostate cancer was applied, this increased to 5% (15/301) of the study population. INTERPRETATION: The 5-year risk of being diagnosed with significant prostate cancer after a prebiopsy low-suspicion prebiopsy biparametric magnetic resonance imaging result was 1·7%.

International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer.

BACKGROUND: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. METHODS: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. RESULTS: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). CONCLUSIONS: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.

For men enrolled in active surveillance, pre-biopsy biparametric magnetic resonance imaging significantly reduces the risk of reclassification and disease progression after 1 year.

AIMS: To assess the level of disease progression at confirmatory staging biopsies after 1 year of active surveillance (AS) and compare the detection rate of significant prostate cancers (PCas) in patients who underwent pre-biopsy biparametric magnetic resonance imaging (bpMRI) before the first set of diagnostic transrectal ultrasonography-guided biopsies (TRUS-bx) with the detection rate in patients who did not undergo pre-biopsy bpMRI. MATERIALS AND METHODS: Comparison of two patient groups enrolled in AS. Patients in Group A (n = 127) underwent pre-biopsy bpMRI followed by TRUS-bx ± targeted biopsies. Patients in Group B (n = 127) were enrolled in AS based on biopsy results from TRUS-bx only. RESULTS: Overall, 6% of the patients in Group A and 20% of the patients in Group B had an upgrade in Gleason grade from insignificant to significant PCa at confirmatory staging biopsies (odds ratio [OR], 3.5; p = .002; 95% confidence interval [CI], 1.6-7.9). CONCLUSIONS: Patients who underwent pre-biopsy bpMRI before the first set of diagnostic biopsies had a reduced risk of reclassification and disease progression after 1 year of AS. Thus, pre-biopsy bpMRI improves the selection of men who should be enrolled in AS.

Comparison of bi- and multiparametric magnetic resonance imaging to select men for active surveillance.

BACKGROUND: Active surveillance of men with prostate cancer relies on accurate risk assessments because it aims to avoid or delay invasive therapies and reduce overtreatment. PURPOSE: To compare the diagnostic performance of pre-biopsy biparametric magnetic resonance imaging (MRI) with confirmatory multiparametric MRI in selecting men for active surveillance. MATERIAL AND METHODS: The study population included biopsy-naïve men with clinical suspicion of prostate cancer undergoing biparametric MRI followed by combined (standard plus MRI targeted) biopsies. Men diagnosed with prostate cancer who were subsequently enrolled in active surveillance and underwent a confirmatory multiparametric MRI within three months of diagnosis were included in the study. Discrepancies between the pre-biopsy biparametric MRI and the confirmatory multiparametric MRI were assessed. RESULTS: Overall, 101 men (median age = 64 years; median prostate-specific-antigen level = 6.3 ng/mL) were included. Nine patients were re-biopsied after multiparametric MRI for the following reasons: suspicion of targeting error (three patients); a new suspicious lesion detected by multiparametric MRI (five patients); and an increase in tumor volume (one patient) compared with biparametric MRI. Confirmatory biopsies showed a Gleason grade group (GG) upgrade of ≥2 in 4/6 patients with suspicion of more advanced disease (missed suspicious lesion, increase in tumor volume) on multiparametric MRI. However, although multiparametric MRI subsequently detected a GG ≥ 2 prostate cancer lesion missed by biparametric MRI in 4% (4/101) of included men, the difference did not reach statistical significance (McNemar, P = 0.133). CONCLUSION: Biparametric MRI could be used to select men eligible for active surveillance and a confirmatory multiparametric MRI performed shortly after inclusion seems unnecessary.

Prebiopsy Biparametric Magnetic Resonance Imaging Combined with Prostate-specific Antigen Density in Detecting and Ruling out Gleason 7-10 Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) combined with prostate-specific-antigen density (PSAd) enhances the detection of significant prostate cancer (sPCa). However, it is unclear whether simple biparametric (bp) MRI, which reduces scan sequences, time, and cost, may be an equally effective noninvasive tool for detecting and ruling out sPCa and avoiding biopsies in biopsy-naïve men. OBJECTIVE: To assess the diagnostic accuracy, predictive values, and best biopsy strategy combining bpMRI and PSAd in detecting and ruling out sPCa (Gleason score ≥7). DESIGN, SETTING, AND PARTICIPANTS: Assessment of 808 biopsy-naïve men with clinical suspicion of localised PCa (prostate-specific antigen <20ng/ml, rectal examination

Magnetic resonance imaging-transrectal ultrasound image fusion guidance of prostate biopsies: current status, challenges and future perspectives.

The use of multiparametric magnetic resonance imaging (mpMRI) in prostate cancer (PCa) diagnosis is rapidly evolving to try to overcome the limitations of the current diagnostic pathway using systematic transrectal ultrasound-guided biopsies (TRUSbx) for all men with clinical suspicion of PCa. Prostate mpMRI allows for high quality lesion detection and characterization and has been shown to improve detection of significant PCa with a more accurate Gleason score grading. Suspicious lesions can be stratified by suspicion and sampled by selective MRI-guided targeted biopsies (TBx) for improved diagnostic accuracy. Several TBx methods have been established and include MRI/TRUS image fusion biopsies (cognitive or software-assisted) and in-bore biopsies, but none have yet proven superior in clinical practice. However, while MRI in-bore biopsy is not routinely used due to its costs and limited availability, MRI/TRUS image fusion is rapidly embraced as it allows skilled urologists to perform TBx in an outpatient clinic. Furthermore, it gives the operator the advantage of adding TBx to the systematic standard biopsy scheme, which is the currently recommended approach. With the anticipated increased future use of prebiopsy mpMRI, a more widespread implementation of MRI/TRUS image fusion platforms is concurrently expected in clinical practice. Therefore, the objective of this review is to assess the current status, challenges and future perspectives of prostate MRI/TRUS image fusion biopsies.

A predictive model based on biparametric magnetic resonance imaging and clinical parameters for improved risk assessment and selection of biopsy-naïve men for prostate biopsies.

BACKGROUND: Prostate cancer risk prediction models and multiparametric magnetic resonance imaging (mpMRI) are used for individualised pre-biopsy risk assessment. However, biparametric MRI (bpMRI) has emerged as a simpler, more rapid MRI approach (fewer scan sequences, no intravenous contrast-media) to reduce costs and facilitate a more widespread clinical implementation. It is unknown how bpMRI and risk models perform conjointly. Therefore, the objective was to develop a predictive model for significant prostate cancer (sPCa) in biopsy-naive men based on bpMRI findings and clinical parameters. METHODS: Eight hundred and seventy-six biopsy-naive men with clinical suspicion of prostate cancer (prostate-specific antigen, <50 ng/mL; tumour stage,

Assessment of prostate cancer prognostic Gleason grade group using zonal-specific features extracted from biparametric MRI using a KNN classifier.

PURPOSE: To automatically assess the aggressiveness of prostate cancer (PCa) lesions using zonal-specific image features extracted from diffusion weighted imaging (DWI) and T2W MRI. METHODS: Region of interest was extracted from DWI (peripheral zone) and T2W MRI (transitional zone and anterior fibromuscular stroma) around the center of 112 PCa lesions from 99 patients. Image histogram and texture features, 38 in total, were used together with a k-nearest neighbor classifier to classify lesions into their respective prognostic Grade Group (GG) (proposed by the International Society of Urological Pathology 2014 consensus conference). A semi-exhaustive feature search was performed (1-6 features in each feature set) and validated using threefold stratified cross validation in a one-versus-rest classification setup. RESULTS: Classifying PCa lesions into GGs resulted in AUC of 0.87, 0.88, 0.96, 0.98, and 0.91 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5 for the peripheral zone, respectively. The results for transitional zone and anterior fibromuscular stroma were AUC of 0.85, 0.89, 0.83, 0.94, and 0.86 for GG1, GG2, GG1 + 2, GG3, and GG4 + 5, respectively. CONCLUSION: This study showed promising results with reasonable AUC values for classification of all GG indicating that zonal-specific imaging features from DWI and T2W MRI can be used to differentiate between PCa lesions of various aggressiveness.

Assessment of the Diagnostic Accuracy of Biparametric Magnetic Resonance Imaging for Prostate Cancer in Biopsy-Naive Men: The Biparametric MRI for Detection of Prostate Cancer (BIDOC) Study.

Importance: Multiparametric magnetic resonance imaging (MRI) enhances detection and risk stratification for significant prostate cancer but is time-consuming (approximately 40 minutes) and expensive. Rapid and simpler (approximately 15-minute) biparametric MRI (bpMRI) using fewer scan sequences could be implemented as a prostate MRI triage test on a larger scale before performing biopsies. Objectives: To assess the diagnostic accuracy and negative predictive value (NPV) of a novel bpMRI method in biopsy-naive men in detecting and ruling out significant prostate cancer in confirmatory biopsies. Design, Setting, and Participants: A single-institutional, paired, prospective cohort study of biopsy-naive men with clinical suspicion of prostate cancer from November 1, 2015, to June 15, 2017. Interventions: All patients underwent bpMRI (T2-weighted and diffusion-weighted imaging) followed by standard transrectal ultrasound-guided biopsies (all men) and targeted biopsies of men with suspicious bpMRI findings. Main Outcomes and Measures: Suspicion grades of bpMRI, biopsy results, and NPV of bpMRI were evaluated for detection of or ruling out significant prostate cancer (Gleason score ≥4 + 3 or maximum cancerous core length >50% for Gleason score 3 + 4). We compared the diagnostic performance of standard biopsies in all men vs standard plus targeted (combined) biopsies restricted to men with suspicious bpMRI findings. The reference standard was combined biopsy results from all men. Results: A total of 1020 men were enrolled, with a median age of 67 years (interquartile range, 61-71 years) and a median prostate-specific antigen level of 8.0 ng/mL (interquartile range, 5.7-13.0 ng/mL). Combined biopsies detected any and significant prostate cancer in 655 of 1020 men (64%) and 404 of 1020 men (40%), respectively. Restricting combined biopsies to men with suspicious bpMRI findings meant 305 of 1020 men (30%) with low-suspicious bpMRIs could avoid prostate biopsies (biopsy in 715 men with suspicious bpMRIs vs all 1020 men who required standard biopsies [70%]; P < .001). Significant prostate cancer diagnoses were improved by 11% (396 vs 351 men; P < .001), and insignificant prostate cancer diagnoses were reduced by 40% (173 vs 288 men; P < .001) compared with our current diagnostic standard, standard biopsies alone in all men. The NPV of bpMRI findings in ruling out significant prostate cancer was 97% (95% CI, 95%-99%). Conclusions and Relevance: Low-suspicion bpMRI has a high NPV in ruling out significant prostate cancer in biopsy-naive men. Using a simple and rapid bpMRI method as a triage test seems to improve risk stratification and may be used to exclude aggressive disease and avoid unnecessary biopsies with its inherent risks. Future studies are needed to fully explore its role in clinical prostate cancer management.

Multiparametric MRI in men with clinical suspicion of prostate cancer undergoing repeat biopsy: a prospective comparison with clinical findings and histopathology.

Background Multiparametric magnetic resonance imaging (mpMRI) can improve detection of clinically significant prostate cancer (csPCa). Purpose To compare mpMRI score subgroups to systematic transrectal ultrasound-guided biopsies (TRUSbx) and prostate-specific antigen (PSA)-based findings for detection of csPCa in men undergoing repeat biopsies. Material and Methods MpMRI was performed prior to re-biopsy in 289 prospectively enrolled patients. All underwent repeat TRUSbx followed by targeted biopsies (MRITB) of any mpMRI-identified lesion. MpMRI suspicion grade, PSA level, and density (PSAd) were compared with biopsy results and further matched to the radical prostatectomy (RP) specimen if available. Results PCa was detected in 128/289 (44%) patients with median age, PSA, and prior negative TRUSbx of 64 (interquartile range [IQR] = 59-67), 12.0 ng/mL (IQR = 8.3-19.1), and 2 (IQR = 1-3), respectively. TRUSbx detected PCa in 108/289 (37%) patients, of which 49 (45%) had insignificant cancer. MRITB was performed in 271/289 (94%) patients and detected PCa in 96 (35%) with 78 (81%) having csPCa. MpMRI scores showed a high association between suspicion level and biopsy results on both lesion and patient level ( P < 0.001). MpMRI was better than PSA and PSAd ( P < 0.001) to identify patients with missed csPCa. In total, 64/128 (50%) patients underwent RP; 60/64 had csPCa. MpMRI was significantly better in predicting csPCa on RP compared with TRUSbx ( P = 0.019) as MRITB and TRUSbx correctly identified 47/60 (78%) and 35/60 (58%) patients, respectively. Conclusion MpMRI improves detection of missed csPCa and suspicion scores correlate well with biopsy and RP results on both patient and lesion level.

Where Do Transrectal Ultrasound- and Magnetic Resonance Imaging-guided Biopsies Miss Significant Prostate Cancer?

OBJECTIVE: To identify the location of missed significant prostate cancer (sPCa) lesions by transrectal ultrasound-guided biopsy (TRUSbx) and multiparametric magnetic resonance imaging-guided biopsy (mpMRIbx) in men undergoing repeat biopsies. MATERIALS AND METHODS: A total of 289 men with prior negative TRUSbx underwent multiparametric magnetic resonance imaging. The location of any suspicious lesion was registered and scored using Prostate Imaging Reporting and Data System version 1 classification according to the likelihood of being sPCa. All patients underwent repeat transrectal ultrasound-guided biopsy (reTRUSbx) and targeted mpMRIbx (image fusion) of any suspicious lesion. Biopsy results were compared and the locations of missed sPCa lesions were registered. Cancer significance was defined as (1) any core with a Gleason score of >6, (2) cancer core involvement of ≥50% and for reTRUSbx on patient level, and (3) the presence of ≥3 positive cores. RESULTS: Of the 289 patients, prostate cancer was detected in 128 (44%) with 88 (30%) having sPCa. Overall, 165 separate prostate cancer lesions were detected with 100 being sPCa. Of these, mpMRIbx and reTRUSbx detected 90% (90/100) and 68% (68/100), respectively. The majority of sPCa lesions (78%) missed by primary TRUSbx were located either anteriorly or in the apical region. Missed sPCa lesions at repeat biopsy were primarily located anteriorly (84%) for reTRUSbx (n = 27/32) and posterolateral midprostatic (60%) for mpMRIbx (n = 6/10). CONCLUSION: Both TRUSbx and mpMRIbx missed sPCa lesions in specific segments of the prostate. Missed sPCa lesions at repeat biopsy were primarily located anteriorly for TRUSbx and posterolateral midprostatic for mpMRIbx. Localization of these segments may improve biopsy techniques in men undergoing repeat biopsies.

A Prospective Comparison of Selective Multiparametric Magnetic Resonance Imaging Fusion-Targeted and Systematic Transrectal Ultrasound-Guided Biopsies for Detecting Prostate Cancer in Men Undergoing Repeated Biopsies.

INTRODUCTION: The aim of the study was to compare the prostate cancer (PCa) detection rate of systematic transrectal ultrasound-guided biopsies (TRUS-bx) and multiparametric-MRI targeted biopsies (mp-MRI-bx) in a repeat biopsy setting and evaluate the clinical significance following an "MRI-targeted-only" approach. MATERIALS AND METHODS: Patients with prior negative biopsies underwent prostatic multiparametric-MRI that was scored using the Prostate Imaging Reporting and Data System (PI-RADS) classification. All underwent both repeated TRUS-bx and mp-MRI-bx using image fusion of any PI-RADS ≥3 lesion. Biopsy results from TRUS-bx, mp-MRI-bx, and the combination were compared. RESULTS: PCa was detected in 89 out of 206 (43%) patients. Of these, 64 (31%) and 74 (36%) patients were detected using mp-MRI-bx and TRUS-bx, respectively. Overall, mp-MRI-bx detected fewer patients with low-grade (Gleason score [GS] 3 + 3) cancers (14/64 vs. 41/74) and more patients with intermediate/high-grade cancers (GS ≥3 + 4) (50/64 vs. 33/74) using fewer biopsy cores compared with TRUS-bx (p < 0.001). Using an "MRI-targeted-only" approach in men with PI-RADS ≥3 lesions reduced the number of men requiring repeated biopsies by 50%, decreased low-grade cancer diagnoses by 66%, and increased intermediate/high-grade cancer diagnoses by 52%. CONCLUSIONS: MRI-targeted biopsies have a high detection rate for significant PCa in patients with prior negative transrectal ultrasound-guided biopsies and preferentially detect intermediate/high-grade compared with low-grade tumors.

Magnetic resonance imaging-guided biopsies may improve diagnosis in biopsy-naive men with suspicion of prostate cancer.

INTRODUCTION: The purpose of this pilot study was to investigate whether a short prostate biparametric magnetic resonance imaging (bp-MRI) protocol provides a valuable diagnostic addition for biopsy guidance in biopsy-naive men with a suspicion of prostate cancer (PCa). METHODS: A total of 62 biopsy-naive patients referred to a systematic transrectal ultrasound biopsy (TRUS-bx) due to suspicion of PCa were prospectively enrolled. Bp-MRI was performed before biopsy. All lesions were scored according to the modified Prostate Imaging Reporting and Data System (PI-RADS) version 2. All patients underwent TRUS-bx followed by bp-MRI-guided biopsies (bp-MRI-bx) under MRI/TRUS image fusion from any bp-MRI suspicious lesions not obviously targeted by TRUS-bx. RESULTS: PCa was found in 42 (68%) and 32 (52%) patients by TRUS-bx and bp-MRI-bx, respectively. Bp-MRI-bx de-tected PCa in one patient who had been missed by TRUS-bx, and found the highest Gleason score (GS) in 13 (30%) patients leading to an overall GS upgrade in six (14%) patients. Bp-MRI missed nine patients with GS = 6 and two with a GS = 7 (3 + 4), all of whom were diagnosed by TRUS-bx. CONCLUSIONS: Addition of bp-MRI-bx to routine TRUS-bx seems feasible in biopsy-naive patients and may improve the detection of aggressive PCa in first-round biopsies. This pilot study thus provides an incentive for a larger investigation. FUNDING: Costs were covered by the Department of Radiology, Herlev Hospital, Denmark. TRIAL REGISTRATION: This study was registered with the Danish Data Protection Agency (HEH-2015-054, I-Suite no: 03775) and with the Committee for Health Research Ethics (no. H-15009341).

Multiparametric MRI in detection and staging of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related mortality and the most frequently diagnosed male malignant disease among men in the Nordic countries. The manifestation of PCa ranges from indolent to highly aggressive disease and due to this high variation in PCa progression, the diagnosis and subsequent treatment planning can be challenging. The current diagnostic approach with PSA testing and digital rectal examination followed by transrectal ultrasound biopsies (TRUS-bx) lack in both sensitivity and specificity in PCa detection and offers limited information about the aggressiveness and stage of the cancer. Scientific work supports the rapidly growing use of multiparametric magnetic resonance imaging (mp-MRI) as the most sensitive and specific imaging tool for detection, lesion characterisation and staging of PCa. However, the experience with mp-MRI in PCa management in Denmark has been very limited. Therefore, we carried out this PhD project based on three original studies to evaluate the use of mp-MRI in detection, assessment of biological aggression and staging of PCa in a Danish setup with limited experience in mp-MRI prostate diagnostics. The aim was to assess whether mp-MRI could 1) improve the overall detection rate of clinically significant PCa previously missed by TRUS-bx, 2) identify patients with extracapsular tumour extension and 3) categorize the histopathological aggressiveness based on diffusion-weighted imaging. MATERIAL AND METHODS: Study I included patients with a history of negative TRUS-bx and persistent suspicion of PCa scheduled for repeated biopsies. Mp-MRI was performed prior to the biopsies and analysed for suspicious lesions. All lesions were scored according to the PIRADS classification from the European Society of Urogenital Radiology's (ESUR) MR prostate guidelines. The lesions were given a sum of scores (ranging 3-15) and classified overall on a Likert five-point scale according to the probability of clinically significant malignancy being present. All patients underwent systematic TRUS-bx (ten cores) and visual mp-MRI-targeted biopsies (mp-MRI-bx) under TRUS-guidance of any mp-MRI-suspicious lesion not hit on systematic TRUS-bx. Study II included patients with clinically localised PCa (cT1-T2) determined by digital rectal examination and/or TRUS and scheduled for radical prostatectomy (RP). Mp-MRI was performed prior to RP, and all lesions were evaluated according to the PIRADS classification and the extracapsular extension (ECE) risk scoring from the ESUR MR prostate guidelines. The images were evaluated by two readers with different experience in mp-MRI interpretation. An mp-MRI T-stage (cTMRI) and an ECE risk score were assigned. Additionally, suspicion of ECE was dichotomised into either organ-confined disease or ECE based on tumour characteristics and personal opinion incorporating functional imaging findings. The RP histopathological results served as standard reference. Study III included patients from study II, where mean ADCtumour values from all malignant tumour foci ≥ 5 mm identified on histopathology were measured on the corresponding diffusion-weighted imaging ADCmap. An ADCbenign value was obtained from a non-cancerous area using the histopathological map as a reference to calculate the ADCratio (ADCtumour divided by ADCbenign). The ADC measurements (ADCtumour and ADCratio values) were correlated with the Gleason score (GS) from each tumour foci. RESULTS: Eighty-three patients were included in study I. PCa was found in 39/83 (47%) and both the PIRADS summation score and the over-all Likert classification showed a high correlation with biopsy results (p < 0.0001). Five patients (13%) had PCa detected only on mp-MRI-bx outside the systematic biopsy areas (p = 0.025) and another 7 patients (21%) had an overall GS upgrade of at least one grade (p = 0.037) based on the mp-MRI-bx. Clinical significant PCa was found in 37/39 patients according to the Epstein criteria (2004). Eighty-seven patients were included in study II and underwent mp-MRI before RP. The correlation between cTMRI and pT showed a spearman rho correlation of 0.658 (p < 0.001) and 0.306 (p = 0.004) with a weighted kappa of 0.585 [CI 0.44;0.73] and 0.22 [CI 0.09;0.35] for reader A and reader B, respectively. The prevalence of ECE after RP was 31/87 (36%). ECE risk scoring showed an AUC of 0.65-0.86 on the ROC-curve for readers and a sensitivity, specificity and diagnostic accuracy of 81% (CI 63;93),78% (CI 66;88) and 79% at the best cut-off level (risk score ≥ 4) for the most experienced reader. When tumour characteristics were influenced by personal opinion and functional imaging, the sensitivity, specificity and diagnostic accuracy for prediction of ECE changed to 74% (CI 55;88), 88% (CI 76;95) and 83% for reader A and 61% (CI 0.42;0.78), 77% (CI 0.64;0.87) and 71% for reader B, respectively. Seventy-one patients were included in study III. The association between ADC measurements and GS showed a significantly negative correlation (p < 0.001) with spearman rho for ADCtumour (-0.421) and ADCratio (-0.649), respectively. There was a statistical significant difference between both ADC measurements and the GS groups for all tumours (p < 0.001). ROC-curve analysis showed an overall AUC of 0.73 (ADCtumour) to 0.80 (ADCratio) in discriminating GS 6 from GS ≥ 7 (3+4) tumours. The AUC remained virtually unchanged at 0.72 (ADCtumour), but increased to 0.90 (ADCratio) when discriminating GS ≤ 7 (3+4) from GS ≥ 7 (4+3). CONCLUSION: Mp-MRI prior to repeated biopsies can improve the detection rate of clinically significant PCa and allow for a more accurate GS by combining standard TRUS-bx with mp-MRI-targeted biopsies under visual TRUS-guidance. Mp-MRI can provide valuable information about the histopathological aggressiveness of a PCa lesion and the tumour stage with possible ECE can be assessed in the pre-therapeutic setting providing important additional information for optimal patient-tailored treatment planning.