Micro-ultrasound-guided biopsies versus systematic biopsies in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. METHODS: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. RESULTS: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I2 = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I2 = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis. CONCLUSION: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

OBJECTIVE: To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. METHODS: From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. RESULTS: Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. CONCLUSIONS: PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer.

PURPOSE: Develop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. METHODS: 64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity, and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. RESULTS: 64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA ( +) 22Rv1 cells than PSMA ( -) PC-3 cells (5.59 ± 0.36 and 1.97 ± 0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 6 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound-guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. CONCLUSION: 64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.

Comparative influence of cribriform growth and percent Gleason 4 in prostatic biopsies with Gleason 3+4 cancer.

The International Society of Urological Pathology endorses specifying presence of cribriform architecture in Gleason (G)4 prostate cancer because of cribriform's aggressiveness. The relative effect of cribriform presence versus percentage G4 within grade group (GG)2 or 3 was uncertain. 194 men's biopsies with GG2 with or without cribriform (excluding glomeruloid from cribriform) and GG3 without cribriform (controls) from 4 years were reviewed. 173 cases had follow-up including 147 GG2 (15/147 or 10% had cribriform) and 26 GG3. Effects of total tumor specimen involvement, %Gleason 4, and cribriform were stratified into prostatectomy (n = 90), radiotherapy (n = 61), and watching waiting (n = 22) groups. Median follow-up duration was 3.32 years (range 1.90-6.18). Biochemical failures in the above 3 cohorts numbered 9 (9/90; 10%), 5 (5/61; 8%), and 13 (13/22; 59%) respectively. In all groups, (GG2+ GG3, n = 173), the HR for C pattern was 1.64. In GG2, cribriform presence (considering glomeruloid as non-cribriform) conferred a hazard ratio (HR) of 1.51 (p = 0.48). It was 1.38, excluding glomeruloid. In watchful waiting cohort only, presence of C conferred a HR of 2.62 (p = 0.086). All remaining comparisons including percent G4, remained not significant. Thus, only in WW group did cribriform pattern presence approach significance. Detection of differences otherwise was not feasible, probably because: 1) biochemical failure is too rare in GG2 cancer; 2) cribriform frequency was only 10% in GG2 (in current study), less than in higher-grade cancer. 3) Use of biopsy tissue is subject to sampling variation which may undersample cribriform pattern, though biopsy forms the basis of treatment decisions.

Decreased accuracy of the prostate cancer EAU risk group classification in the era of imaging-guided diagnostic pathway: proposal for a new classification based on MRI-targeted biopsies and early oncologic outcomes after surgery.

PURPOSE: To assess the performance of EAU risk classification in PCa patients according to the biopsy pathway (standard versus MRI guided) and to develop a new, more accurate, targeted biopsy (TB)-based classification. MATERIALS AND METHODS: We included 1345 patients consecutively operated by radical prostatectomy (RP) since 2014, when MRI and TB were introduced in the diagnostic pathway. Patients underwent systematic biopsy (SB) only (n = 819) or SB and TB (n = 526) prior to RP during the same time period. Pathological and biochemical outcomes were compared between PCa men undergoing SB (SB cohort) and a combination of TB and SB (TB cohort). Kaplan-Meier and Cox regression models were used to assess biochemical recurrence-free survival (RFS). RESULTS: Both cohorts were comparable regarding final pathology and RFS (p = 0.538). The EAU risk classification accurately predicted outcomes in SB cohort, but did not significantly separate low from intermediate risk in TB cohort (p = 0.791). In TB cohort, the new proposed three-group risk classification significantly improved the recurrence risk prediction compared with the EAU risk classification: HR 4 (versus HR 1.2, p = 0.009) for intermediate, and HR 15 (versus HR 6.5, p < 0.001) in high-risk groups, respectively. A fourth group defining very high-risk cases (≥ T2c clinical stage or grade group 5) was also proposed. CONCLUSIONS: The new classification integrating TB findings we propose meaningfully improves the recurrence prediction after surgery in patients undergoing a TB-based diagnostic pathway, compared with standard EAU risk classification which is still relevant for patients undergoing only SB. External validation is needed.

Performance of systematic, MRI-targeted biopsies alone or in combination for the prediction of unfavourable disease in MRI-positive low-risk prostate cancer patients eligible for active surveillance.

PURPOSE: To assess the upstaging/upgrading rates of low-risk prostate cancer (PCa) according to the biopsy scheme used (systematic (SB), targeted biopsies (TB), or both) in the setting of positive pre-biopsy MRI. PATIENTS AND METHODS: We included 143 consecutive men fulfilling the Toronto University active surveillance (AS) criteria who underwent a pre-biopsy positive MRI, a combination of SB and software-based fusion TB, and a radical prostatectomy, in two expert centres. The primary endpoints were the pathological upgrading and upstaging rates. Overall unfavourable disease (OUD) was defined by any pT3-4 and/or pN1 and/or ≥ GG 3. RESULTS: Using TB alone would have missed 21.7% of cancers including 16.7% of ≥ GG 3. The use of TB was significantly associated with a lower risk of ≥ Grade Group (GG) 3 disease (p < 0.006) in RP specimens. Combination of SB and TB lowered this risk by 39%, compared with TB alone. The biopsy scheme did not affect the upstaging rates which were substantial even in case of combination scheme (from 37 to 46%). OUD was detected in approximately 50% of cases. The presence of high grade on TB was the only independent predictive factor for both ≥ GG 2 (p = 0.015) and ≥ GG 3 (p = 0.023) in RP specimens. CONCLUSIONS: High grade on TB biopsies represented the major predictor of upgrading. Combination of SB and TB better defined the sub-group of patients having the lowest risk of reclassification, compared with TB or SB alone. The risk of non-organ-confined disease remained high, and could not be accurately predicted by MRI or systematic/targeted biopsy features.

Active surveillance eligibility of MRI-positive patients with grade group 2 prostate cancer: a pathological study.

PURPOSE: To assess the final pathology risk in MRI-positive grade group (GG) 2 prostate cancer (PCa) patients undergoing targeted (TB) and systematic (SB) biopsies, and thereby, the possibility of active surveillance (AS) in this population. PATIENTS AND METHODS: We included 242 consecutive men diagnosed with GG2 PCa by a combination of SB and software-based fusion TB undergoing a radical prostatectomy (RP). The primary endpoints were the pathological findings in RP specimens, including favourable disease which was defined by a pT2 and GG1-2 disease. RESULTS: The rate of upgrading was 33% including 3% of GG 4-5 disease. MRI lesion size (p = 0.038) and tumor length per core (p < 0.001) were significantly lower in case of favourable pathology. Only 34.2% of not organ-confined disease was reported when only SB were positive, compared with 45.7% and 57.1% when GG2 was detected on TB only and on TB plus SB, respectively (p = 0.035). The number of positive cores on SB was significantly higher in not organ-confined disease (4.3 versus 2.9; p = 0.005). The risk of not organ-confined disease was only 20.8% in men who had a PSAD ≤ 0.20 ng/ml/gr, 1-2 positive biopsies and a maximal tumor length ≤ 6 mm per core, compared with 52.3% in men who did not fulfil all these criteria (p = 0.003). CONCLUSIONS: This study identified clinical, imaging, and pathological factors that were significantly associated with the final pathology risk. In case of positive MRI followed by TB showing GG2, AS could be offered in patients having a PSAD ≤ 0.20, a tumor length ≤ 6 mm and 1-2 positive cores.

A 12-year follow-up of ANNA/C-TRUS image-targeted biopsies in patients suspicious for prostate cancer.

PURPOSE: PSA screening has been rehabilitated. PSA is not specific and can be elevated by benign reasons. Additionally, a subgroup of patients with prostate hyperplasia may harbor prostate cancer (PCa). During monitoring, the clinician aims to detect significant tumors in time, submitting patients to minimal psychological and physical burden, especially in men with high serum PSA and repeat biopsies. We aimed to determine long-term outcomes with respect to ANNA/C-TRUS ability to detect PCa with six targeted biopsies. METHODS: A subset of 71 patients were enrolled. During monitoring, they were subjected to primary, secondary, or even multiple prostate biopsies when needed. Protocol monitoring included PSA measurements, digital rectal examination (DRE) and imaging. RESULTS: The median follow-up was 12 years. Forty-one patients had a history of negative systematic random biopsies (1-3 sessions). Their age ranges 62-85 years, PSA 0.5-47.3 ng/ml, and the median prostate volume 11-255 cc. During monitoring, 15 patients were diagnosed with PCa. Only two harbored aggressive tumors. The median time to diagnosis was 6 years. All PCa patients are free from biochemical relapse. From the remaining 56 patients, 11 did not have any biopsies, 12 had one, 13 had two, and 20 had three or more biopsy sessions. CONCLUSIONS: ANNA/C-TRUS is a useful method monitoring patients with a risk of PCa. 50-75% of the usually performed biopsy cores could be spared and, after 12 years, 97% of the patients were either without evidence of a PCa or were diagnosed with a good prognosis tumor.

[Pathology findings after radical prostatectomy for prostate cancer in patients eligible for active surveillance: Contribution of multiparametric MRI to treatment decision]. / Résultats anatomopathologiques après prostatectomie totale pour cancer chez des patients éligibles à une surveillance active : apport de l'IRM multiparamétrique dans la décision de traitement.

OBJECTIVES: To analyze, in patients with prostate cancer (PC) potentially eligible for active surveillance (AS), whether multiparametric-MRI (mp-MRI) predicts presence of clinically significant cancer on radical prostatectomy (RP) specimen. METHODS: We identified 77 men with PC eligible for AS (PSA≤15ng/mL, stage≤T2a, Gleason score≤6, up to 3 positive cores, maximal cancer core length≤5mm) who underwent RP between 01/2008 and 08/2015. All patients had prebiopsy mp-MRI followed by systematic±targeted biopsies. For each patient, the likelihood of the presence of cancer on mp-MRI was assigned using Likert scale (1 to 5). The predictive factors for the presence of significant cancer on RP specimen (Gleason score≥7 and/or tumoral maximal diameter>10mm) were evaluated using logistic regression. RESULTS: Median age was 61 and median PSA was 6.7ng/mL. Overall, 49 (64%) patients had a positive mp-MRI (score≥3). Clinically significant cancer on RP specimen was found in 45 (58%) patients (69% in MRI-positive patients vs 39% in MRI-negative patients). In multivariate analysis, a positive MRI was a predictive factor for the presence of significant cancer on the surgical specimen (OR=3.0; CI95% [1.01-8.88]; P=0.04), as was age (OR=1.17; CI95% [1.05-1.31]; P=0.004) and PSAD (OR=1.10; CI95% [1.01-1.20]; P=0.02). CONCLUSION: Mp-MRI is a useful exam for selecting patients eligible for AS even if the situation remains unclear after prostate biopsies including targeted biopsies. Upon confirmation by further studies, mp-MRI should be considered as an independent criterion before entering an AS program. LEVEL OF EVIDENCE: 4.

[Pathological findings of visible and non-visible tumors on multiparametric magnetic resonance imaging (MRI) prior to radical prostatectomy]. / Caractéristiques anatomopathologiques des tumeurs apparentes et non apparentes en IRM multiparamétrique de la prostate avant prostatectomie totale.

INTRODUCTION: As urologists are questioned about the overtreatment of localized prostate cancer, multiparametric MRI can diagnose significant prostate cancer thanks to targeted biopsies. However, some tumors cannot be detected by MRI. What are the pathological characteristics of those tumors? MATERIALS AND METHODS: We have selected 144 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on systematic and targeted biopsies (Koelis®) according to multiparametric MRI findings. On MRI, each suspicious area was graded according to the PI-RADS score v1.0. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or a tumor volume greater than 0,5cm3 were considered significant. The grade-four tumoral volume was calculated by multiplying the tumoral volume by grade 4 tumoral percentage. RESULTS: Two hundred and seventy seven tumors were identified. A hundred and thirty nine were non-visible on MRI. They had a significantly lower volume (0.15cm3 versus 1.45cm3, P<0.0001) and a Gleason score significantly lower (P<0.0001) than apparent tumors. 17.3% of non-apparent tumors were significant. Moreover, the grade-four tumoral volume of significant non-apparent tumors was significantly lower than that of significant apparent tumors (0.11cm3 versus 0.66cm3, P<0.0001). CONCLUSION: Non-apparent prostate tumors on multiparametric MRI have a Gleason score, a tumor volume - and consequently - a grade 4 tumor volume significantly lower than apparent tumors. LEVEL OF PROOF: 4.

Role of Perilesional Sampling of Patients Undergoing Fusion Prostate Biopsies.

Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A prospective cohort of patients undergoing transrectal MRI transrectal fusion biopsies were consecutively enrolled. All the patients underwent systematic biopsies (SB), targeted biopsies (TB) and perilesional biopsies within 10 mm from the lesion (PB). The detection rates of different strategies were determined. A total of 262 patients were enrolled. The median age of those enrolled was 70 years. The mean BMI was 27 kg/m2, and the mean and prostate volume was 52 mL. A PIRADS score ≥ 4 was recorded in 163/262 (40%) patients. Overall, the detection rates of cancer were 43.5% (114/262) and 35% (92/262) for csPCa. The use of the target + peri-target strategy resulted in a detection of 32.8% (86/262) of cancer cases and of 29% (76/262) of csPCa cases (Grade Group > 2). Using the target plus peri-target approach resulted in us missing 18/262 (7%) of the csPCa cases, avoiding the diagnosis of 8/262 (3%) of nsPCa cases. A biopsy strategy including lesional and perilesional sampling could avoid unnecessary prostate biopsies. However, the risk of missing significant cancers is present. Future studies should assess the cost-benefit relationship of different strategies.

MRI-Guided Targeted and Systematic Prostate Biopsies as Prognostic Indicators for Prostate Cancer Treatment Decisions.

The standard procedure for the diagnosis of prostate carcinoma involves the collection of 10-12 systematic biopsies (SBx) from both lobes. MRI-guided targeted biopsies (TBx) from suspicious foci increase the detection rates of clinically significant (cs) PCa. We investigated the extent to which the results of the TBx predicted the tumor board treatment decisions. SBx and TBx were acquired from 150 patients. Risk stratifications and recommendations for interventional therapy (prostatectomy and radiotherapy) or active surveillance were established by interdisciplinary tumor boards. We analyzed how often TBx alone were enough to correctly classify the tumors as well as to indicate interventional therapy and how often the findings of SBx were crucial for therapy decisions. A total of 28/39 (72%) favorable risk tumors were detected in TBx, of which 11/26 (42%) very-low-risk tumors were not detected and 8/13 (62%) low-risk tumors were undergraded. A total of 36/44 (82%) intermediate-risk PCa were present in TBx, of which 4 (9%) were underdiagnosed as a favorable risk tumor. A total of 12/13 (92%) high-risk carcinomas were detected and correctly grouped in TBx. The majority of csPCa were identified by the sampling of TBx alone. The tumor size was underestimated in a proportion of ISUP grade 1 tumors. Systematic biopsy sampling is therefore indicated for the next AS follow-up in these cases.

Assessing the Role of High-resolution Microultrasound Among Naïve Patients with Negative Multiparametric Magnetic Resonance Imaging and a Persistently High Suspicion of Prostate Cancer.

Background: Multiparametric magnetic resonance imaging (mpMRI) is an invaluable diagnostic tool in the decision-making for prostate biopsies (PBx). However, a non-negligible proportion of patients with negative MRI (nMRI) may still harbour prostate cancer (PCa). Objective: To assess whether microultrasound (micro-US) can help in substratifying the presence of PCa and clinically significant PCa (csPCa; ie, any Gleason score ≥7 PCa) in patients with nMRI despite a persistently high clinical suspicion of PCa. Design setting and participants: A total of 125 biopsy-naïve patients who underwent micro-US-guided PBx with the ExactVu system for a persistently high suspicion of PCa despite nMRI were prospectively enrolled. Intervention: The Prostate Risk Identification using micro-US (PRI-MUS) protocol was used to identify suspicious areas; PBx included targeted sampling of PRI-MUS ≥3 areas and systematic sampling. Outcome measurements and statistical analysis: The primary endpoint was the assessment of micro-US diagnostic accuracy in detecting csPCa. Secondary endpoints included determining the proportion of patients with nMRI who may avoid PBx after micro-US or transrectal US, presence of cribriform and intraductal patterns on biopsy core examination, predictors of csPCa in patients presenting with nMRI, and comparing micro-US-targeted and systematic PBx in identifying csPCa. Results and limitations: Considering csPCa detection rate, micro-US showed optimal sensitivity and negative predictive value (respectively, 97.1% and 96.4%), while specificity and positive predictive value were 29.7% and 34.0%, respectively. Twenty-eight (22.4%) patients with a negative micro-US examination could have avoided PBx with one (2.9%) missed csPCa. Cribriform and intraductal patterns were found in 14 (41.2%) and four (11.8%) of csPCa patients, respectively. In multivariable logistic regression models, positive micro-US, age, digital rectal examination, and prostate-specific antigen density ≥0.15 emerged as independent predictors of PCa. Targeted and systematic sampling identified 33 (97.1%) and 26 (76.5%) csPCa cases, respectively. The main limitation of the current study is represented by its retrospective single-centre nature on an operator-dependent technology. Conclusions: Micro-US represents a valuable tool to rule out the presence of csPCa among patients with a persistent clinical suspicion despite nMRI. Patient summary: According to our results, microultrasound (micro-US) may represent an effective tool for the diagnosis of clinically significant prostate cancer in patients with negative magnetic resonance imaging (nMRI), providing high sensitivity and negative predictive value. Further randomised studies are needed to confirm the potential role of micro-US in the diagnostic pathway of patients with a persistent suspicion of prostate cancer despite nMRI.

Ex Vivo Fluorescence Confocal Microscopy (FCM) of Prostate Biopsies Rethought: Opportunities of Intraoperative Examinations of MRI-Guided Targeted Biopsies in Routine Diagnostics.

BACKGROUND: The diagnosis of prostate carcinoma (PCa) requires time- and material-consuming histopathological examinations. Ex vivo fluorescence confocal microscopy (FCM) can detect carcinoma foci in diagnostic biopsies intraoperatively. METHODS: MRI-guided and systematic biopsies were identified in a dataset of our previously published study cohort. Detection rates of clinically relevant tumors were determined in both groups. A retrospective blinded trial was performed to determine how many tumors requiring intervention were detectable via FCM analysis of MRI-guided targeted biopsies alone. RESULTS: MRI-guided targeted biopsies revealed tumors more frequently than systematic biopsies. Carcinomas in need of intervention were reliably represented in the MRI-guided biopsies and were identified in intraoperative FCM microscopy. Combined with serum PSA levels and clinical presentation, 91% of the carcinomas in need of intervention were identified. CONCLUSIONS: Intraoperative FCM analysis of MRI-guided biopsies is a promising approach for the efficient diagnosis of PCa. The method allows a timely assessment of whether a tumor disease requiring intervention is present and can reduce the psychological stress of the patient in the waiting period of the histological finding. Furthermore, this technique can lead to reduction of the total number of biopsies needed for the diagnosis of PCa.

Value of Targeted Biopsies and Combined PSMA PET/CT and mp-MRI Imaging in Locally Recurrent Prostate Cancer after Primary Radiotherapy.

Radiorecurrent prostate cancer is conventionally confirmed using systematic and/or targeted biopsies. The availability of multiparametric (mp) MRI and prostate specific membrane antigen (PSMA) PET/CT has increased diagnostic accuracy. The objective was to determine the positive predictive value (PPV) of combined mp-MRI and PSMA PET/CT and whether pathology verification with MR-targeted biopsies remains necessary for patients with radiorecurrent prostate cancer. Patients with locally recurrent prostate cancer who were referred for 19 Gy single-dose MRI-guided focal salvage high dose rate (HDR) brachytherapy between 2015 and 2018 were included in the current analysis. Patients were selected if they underwent pre-biopsy mp-MRI and PSMA PET/CT. Based on these images, lesions suspect for isolated tumor recurrence were transperineally biopsied using transrectal ultrasound fused with MRI. A total of 41 patients were identified from the database who underwent cognitive targeted (n = 7) or MRI/PSMA-transrectal ultrasound (TRUS) fused targeted (n = 34) biopsies. A total of 40 (97.6%) patients had positive biopsies for recurrent cancer. Five patients initially had negative biopsies (all MRI/PSMA-TRUS fusion targeted), four of whom recurrence was confirmed after a re-biopsy. One (2.4%) patient refused re-biopsy, leading to a positive predictive value (PPV) for combined imaging of 97.6%. Biopsies can therefore safely be withheld when the results of the combined mp-MRI and PSMA PET/CT are conclusive, avoiding an unnecessary invasive and burdensome procedure.

Optimizing MRI-targeted prostate biopsy: the diagnostic benefit of additional targeted biopsy cores.

INTRODUCTION: The optimal number of biopsy cores to obtain during MRI-targeted prostate biopsy remains ill-defined. This study sought to determine the optimal number of targeted biopsy cores to obtain from a region of interest to maximize detection of clinically significant prostate cancer. MATERIALS AND METHODS: Consecutive patients undergoing MRI-targeted prostate biopsy at a single institution that newly implemented a targeted biopsy pathway from May 2017 to February 2018 were prospectively enrolled. Five biopsy cores were obtained and individually analyzed from each region rated ≥3 on PI-RADS v2.0 to determine the incremental diagnostic benefit of each additional targeted biopsy core. Variables associated with increasing Grade Group from the first to fifth biopsy core were assessed. RESULTS: One hundred and four patients (79% for elevated PSA) were enrolled, 82% of which had a prior biopsy. Men with a PI-RADS >3 lesion were more likely to have pathologic upgrading with additional targeted biopsy cores (OR:4.76; 95% CI:2.34-9.70; P < 0.0001), particularly to Grade Group ≥2 (OR:5.16; 95% CI:2.17-12.29; P = 0.0002), compared to men with PI-RADS 3 lesions. Detection of clinically significant cancer increased from 26% to 44% to 52% when comparing the first, third, and fifth biopsy cores amongst men with a PI-RADS >3 lesion and from 1% to 4% to 9% for PI-RADS 3 lesions. Urinary retention was the most common complication, occurring in 6 (5.7%) patients. CONCLUSION: Clinically significant prostate cancer detection is improved with increased number of MRI-targeted biopsy cores, particularly for urologists early in their learning curve.

Diagnostic Accuracy of Microultrasound in Patients with a Suspicion of Prostate Cancer at Magnetic Resonance Imaging: A Single-institutional Prospective Study.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) represents the gold standard for the diagnosis of clinically significant prostate cancer (csPCa). The search for alternative diagnostic techniques is still ongoing. OBJECTIVE: To determine the accuracy of microultrasound (microUS) for the diagnosis of csPCa within prospectively collected cohort of patients with a suspicion of prostate cancer (PCa) according to MRI. DESIGN, SETTING, AND PARTICIPANTS: A total of 320 consecutive patients with at least one Prostate Imaging Reporting and Data System (PIRADS) ≥3 lesion according to MRI were prospectively enrolled. INTERVENTION: All patients received microUS before prostate biopsy using the ExactVu system; the Prostate Risk Identification using microUS (PRI-MUS) protocol was used to identify targets. The urologists were blinded to MRI results until after the microUS targeting was completed. All patients received both targeted (based on either microUS or MRI findings) and randomized biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The sensitivity and specificity of microUS to determine the presence of csPCa (defined as at least one core with a Gleason score ≥7 PCa) were determined. Multivariable logistic regression analysis was fitted to determine the predictors of csPCa. RESULTS AND LIMITATIONS: Clinically significant PCa was diagnosed in 116 (36.3%) patients. The sensitivity and negative predictive value of microUS for csPCa diagnosis were 89.7% and 81.5%, while specificity and positive predictive value were 26.0% and 40.8%, respectively. A combination of microUS-targeted and randomized biopsies would allow diagnosing the same proportion of csPCa as that diagnosed by an approach combining MRI-targeted and randomized biopsies (n = 113; 97.4%), with only three (2.6%) csPCa cases diagnosed by a microUS-targeted and three (2.6%) by an MRI-targeted approach. In a logistic regression model, an increasing PRI-MUS score was an independent predictor of csPCa (p ≤ 0.005). The main limitation of the current study is represented by the fact that all patients had suspicious MRI. CONCLUSIONS: Microultrasound is a promising imaging modality for targeted prostate biopsies. Our results suggest that a microUS-based biopsy strategy may be capable of diagnosing the great majority of cancers, while missing only few patients with csPCa. PATIENT SUMMARY: According to our results, microultrasound (microUS) may represent an effective diagnostic alternative to magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, providing high sensitivity and a high negative predictive value. Further randomized studies are needed to confirm the potential role of microUS in the diagnostic pathway of patients with a suspicion of prostate cancer.

Prostate cancer detection by targeted prostate biopsy using the 3D Navigo system: a prospective study.

PURPOSE: The 3D Navigo™ system is a magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion device for prostate targeted biopsies (TB). Our aim was to evaluate the clinically significant prostate cancer (CSC) detection rate of TB using the 3D Navigo™ system. METHODS: Patients who underwent TB with the 3D Navigo™ system in our center between June 2014 and May 2018 were prospectively included, excluding those who have previously received treatment for prostate cancer. A 3-Tesla MRI imaging was performed before biopsies; findings were reported according to the Prostate Imaging Reporting and Data System version 2 (PIRADS). CSC was defined by an ISUP score ≥ 2. RESULTS: 304 patients underwent TB. Median age was 66 years (51-84). Median PSA was 7.75 ng/ml (0.6-70.0). Median prostate volume was 45.0 ml (15.9-221.7). PCa and CSC were found in 70.4% (214/304) and 47.7% (145/304) of the patients, respectively. The proportion of patients diagnosed with CSC among those with PCa was 67.8% (145/214). There was a significant risk of having a CSC in case of PIRADS score ≥ 4 and 5 (OR 5.0, 95% CI [2.7-9.2], P < 0.001; OR 3.2, 95% CI [1.8-5.5], P < 0.001). PIRADS score was an independent risk factor of having a CSC (OR 4.19, 95% CI [2.49-7.05], P < 0.001). There was no significant difference between pathological outcomes of TB and RP in paired analysis (P = 0.892). There was a correlation between TB and RP specimens for PCa detection (r = 0.60, P < 0.001). CONCLUSION: Detecting CSC with MRI-TRUS fusion targeted biopsies using the 3D Navigo™ system is feasible and safe. We found a positive correlation between TB and RP for ISUP scores.

The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: A single institutional analysis.

INTRODUCTION: Magnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population. MATERIAL AND METHODS: We retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve. RESULTS: Overall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 - 0.843). CONCLUSION: In our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results.

Intercenter reproducibility of software-based fusion biopsies for grade group prediction when targeting suspicious MRI lesions.

PURPOSE: To assess the intercenter reproducibility of software-based fusion targeted biopsy (TB) for grade-group assessment and pretherapeutic evaluation of highly suspicious MRI lesions. PATIENTS AND METHODS: In this study, were included 380 consecutive patients who underwent radical prostatectomy (RP) after prostate cancer diagnosis and a prebiopsy MRI showing Prostate Imaging-Reporting and Data System (PIRADS) score 4 or 5 lesions. All patients underwent systematic biopsies (SB) combined with software-based fusion TB in the 2 centers. Biopsies were only performed by expert urologists or radiologists in a contemporary time frame. The primary endpoint was the center difference of concordance/upgrading rates between biopsy and RP specimens. RESULTS: Pathological features on biopsy and RP specimens were significantly different among centers with more unfavourable disease in center 1. The rate of TB upgrading was 33.6% in center 1 vs. 35.4% (P = 0.860) in center 2. Grading concordance was also comparable among centers (50.0% vs. 47.1%) as well as the SB upgrading rate. Regression analysis did not find any baseline characteristics (Age, prostate-specific antigen, MRI lesions, center) predictive for TB upgrading. These findings were achieved by using fewer TB per lesion in center 1 (2.3 vs. 5.0, P < 0.001), at the expense of more SB cores (14.4 vs. 8.5, P < 0.001). The influence of MRI characteristics (lesion size and number, PIRADS score) on upgrading rates was consistent among centers. CONCLUSIONS: Software-based fusion TB technique leads to comparable outcomes in terms of grade group prediction accuracy in PIRADS 4 to 5 lesions, insignificant between centers, in spite of different non imaging-based aggressiveness features.