Hepatocellular Adenomas: Molecular Basis and Multimodality Imaging Update.

Hepatocellular adenomas (HCAs) are a family of liver tumors that are associated with variable prognoses. Since the initial description of these tumors, the classification of HCAs has expanded and now includes eight distinct genotypic subtypes based on molecular analysis findings. These genotypic subtypes have unique derangements in their cellular biologic makeup that determine their clinical course and may allow noninvasive identification of certain subtypes. Multiphasic MRI performed with hepatobiliary contrast agents remains the best method to noninvasively detect, characterize, and monitor HCAs. HCAs are generally hypointense during the hepatobiliary phase; the ß-catenin-mutated exon 3 subtype and up to a third of inflammatory HCAs are the exception to this characterization. It is important to understand the appearances of HCAs beyond their depictions at MRI, as these tumors are typically identified with other imaging modalities first. The two most feared related complications are bleeding and malignant transformation to hepatocellular carcinoma, although the risk of these complications depends on tumor size, subtype, and clinical factors. Elective surgical resection is recommended for HCAs that are persistently larger than 5 cm, adenomas of any size in men, and all ß-catenin-mutated exon 3 HCAs. Thermal ablation and transarterial embolization are potential alternatives to surgical resection. In the acute setting of a ruptured HCA, patients typically undergo transarterial embolization with or without delayed surgical resection. This update on HCAs includes a review of radiologic-pathologic correlations by subtype and imaging modality, related complications, and management recommendations. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Hepatocellular Adenoma Subtypes Based on 2017 Classification System: Exploratory Study of Gadoxetate Disodium-Enhanced MRI Features With Proposal of a Diagnostic Algorithm.

BACKGROUND. The classification of hepatocellular adenomas (HCAs) was updated in 2017 on the basis of genetic and molecular analysis. OBJECTIVE. The purpose of this article was to evaluate features on gadoxetate disodium-enhanced MRI of HCA subtypes on the basis of the 2017 classification and to propose a diagnostic algorithm for determining subtype using these features. METHODS. This retrospective study included 56 patients (49 women, seven men; mean age, 37 ± 13 [SD] years) with histologically confirmed HCA evaluated by gadoxetate disodium-enhanced MRI from January 2010 to January 2021. Subtypes were reclassified using 2017 criteria: hepatocyte nuclear factor-1α mutated HCA (HHCA), inflammatory HCA (IHCA), ß-catenin exon 3 activated HCA (ß-HCA), mixed inflammatory and ß-HCA (ß-IHCA), sonic hedgehog HCA (shHCA), and unclassified HCA (UHCA). Qualitative MRI features were assessed. Liver-to-lesion contrast enhancement ratios (LLCERs) were measured. Subtypes were compared, and a diagnostic algorithm was proposed. RESULTS. The analysis included 65 HCAs: 16 HHCAs, 31 IHCAs, six ß-HCA, four ß-IHCA, five shHCA, and three UHCAs. HHCAs showed homogeneous diffuse intralesional steatosis in 94%, whereas all other HCAs showed this finding in 0% (p < .001). IHCAs showed the "atoll" sign in 58%, whereas all other HCAs showed this finding in 12% (p < .001). IHCAs showed moderate T2 hyperintensity in 52%, whereas all other HCAs showed this finding in 12% (p < .001). The ß-HCAs and ß-IHCAs occurred in men in 63%, whereas all other HCAs occurred in men in 4% (p < .001). The ß-HCAs and ß-IHCAs had a mean size of 10.1 ± 6.8 cm, whereas all other HCAs had a mean size of 5.1 ± 2.9 cm (p = .03). The ß-HCAs and ß-IHCAs showed fluid components in 60%, whereas all other HCAs showed this finding in 5% (p < .001). Hepatobiliary phase iso- or hyperintensity was observed in 80% of ß-HCAs and ß-IHCAs versus 5% of all other HCAs (p < .001). Hepatobiliary phase LLCER was positive in nine HCAs (eight ß-HCAs and ß-IHCAs; one IHCA). The shHCA and UHCA did not show distinguishing features. The proposed diagnostic algorithm had accuracy of 98% for HHCAs, 83% for IHCAs, and 95% for ß-HCAs or ß-IHCAs. CONCLUSION. Findings on gadoxetate disodium-enhanced MRI, including hepatobiliary phase characteristics, were associated with HCA subtypes using the 2017 classification. CLINICAL IMPACT. The algorithm identified common HCA subtypes with high accuracy, including those with ß-catenin exon 3 mutations.

Colonoscopy Versus Catheter Angiography for Lower Gastrointestinal Bleeding After Localization on CT Angiography.

PURPOSE: The aim of this study was to compare catheter angiography (CA) and colonoscopy outcomes after successful CT angiographic (CTA) localization for patients with overt lower gastrointestinal bleeding (LGIB). METHODS: Seventy-one consecutive patients from two institutions between 2010 and 2020 had both contrast extravasation on CTA imaging in the lower gastrointestinal tract and subsequent CA or colonoscopy. The primary outcome was confirmation of active bleeding during CA or colonoscopy (defined as confirmation yield). The secondary outcomes were to determine therapeutic yield (hemostatic therapy), time to procedure, rebleeding rate, and adverse outcome rates (defined as surgery, acute kidney injury, initiation of dialysis, and overall mortality). Univariate analyses and multivariable analyses with P < .05 were used to determine statistical significance. RESULTS: Forty-four patients underwent CA and 27 underwent colonoscopy. CA had higher overall confirmation yield (55% vs 26%, P = .026), whereas therapeutic yields were similar (70% vs 56%, P = .214). Time to procedure was 5.1 ± 3.4 hours for CA and 15.5 ± 13.6 hours for colonoscopy (P < .001). On multivariable analysis, shorter time to procedure was the only statistically significant predictor of confirmation yield (P = .037) and therapeutic yield (P = .013), whereas procedure, hemoglobin, transfusions, and hemodynamic instability were not. Adverse events and rebleeding were not statistically different between patients who underwent CA and colonoscopy (P > .05). CONCLUSIONS: Shorter time to procedure was the only statistically significant predictor of confirmation and therapeutic yield after CTA localization of LGIB. Because CA can be performed sooner than colonoscopy without increased rates of adverse outcomes or rebleeding, CA may be a reasonable first-line treatment option in patients with CTA localization of LGIB.

Targeted Prostate Biopsy: Umbra, Penumbra, and Value of Perilesional Sampling.

BACKGROUND: Systematic prostate biopsies add to the cancer detection rate of targeted biopsies, but the explanation for that increased sensitivity is not yet clear. OBJECTIVE: To determine and quantify the utility of perilesional biopsies in the detection of clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS: Participants were 2048 men with magnetic resonance imaging (MRI) lesions (grades 3-5) who underwent targeted and systematic prostate biopsy via MRI/ultrasound fusion at University of California Los Angeles and Cornell between 2011 and 2019. The study is a retrospective examination of prospectively acquired data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All biopsy cores (30191), locations of which had been stored digitally in the image-fusion device, were analyzed for tissue pathology and relationship with MRI lesions. A validated Matlab script was used to determine the distance between MRI lesions and cores containing csPCa (3552 cores from 927 men). Significance of distance measurements was determined by multilevel, multivariable logistic regression to account for within patient-biopsy correlation and control for patient characteristics. RESULTS AND LIMITATIONS: Overall, 90% (95% confidence interval [CI] = 89-91) of csPCa cores (3206/3552) were located within a radius of 10 mm from the nearest lesion: 65% (95% CI = 63-67) within the region of interest (ROI) and 26% (95% CI = 24-27) outside the ROI but within the 10-mm "penumbra." The width of the penumbra or concentric band, which enclosed 90% of csPCa, was primarily related to MRI grade of lesion: grade 5, 5 mm; grade 4, 12 mm; grade 3, 16 mm. In 18% (95% CI = 15-20) of patients (166/927), csPCa was diagnosed only by sampling outside the MRI lesion, the yield decreasing with increasing distance. Limitations of MRI interpretation and fusion biopsy performance could affect the utility of these data in individual patients. CONCLUSIONS: Perilesional biopsies, that is, samples taken from a band of 10-mm radius outside MRI lesions (the penumbra), contain most cores of csPCa that are not present within the lesion. These data may help increase the performance characteristics of targeted prostate biopsy. PATIENT SUMMARY: We studied the locations of cancer within the prostate in men undergoing magnetic resonance imaging (MRI)-guided biopsy. We found that not all cancers are located within the MRI lesion, but 90% (95% confidence interval = 89-91) of the cancers arewithin 1 cm of the lesions. Biopsies taken from both within and around MRI lesions provide greater sensitivity for cancer detection than samples taken from the lesion only.

Steady-state ferumoxytol-enhanced MRI: early observations in benign abdominal organ masses and clinical implications.

INTRODUCTION: The off-label use of ferumoxytol as a vascular MR imaging agent is growing rapidly. However, the properties of ferumoxytol suggest that it may play an important role in the detection and characterization of abdominal mass lesions. METHODS: Thirty-six patients with benign abdominal mass lesions who underwent MR angiography with ferumoxytol also had T2-weighted HASTE imaging and fat-suppressed 3D T1-weighted imaging. The T1 and T2 enhancement characteristics of the lesions were analyzed and correlated with other imaging modalities and/or surgical findings and/or clinical follow-up. RESULTS: In all patients with benign masses in the liver (n = 22 patients), spleen (n = 6 patients), kidneys (n = 33 patients), adrenal (n = 2 patients) and pancreas (n = 4 patients), based on the enhancement characteristics with ferumoxytol, readers were confident of the benign nature of the lesions and their conclusions were consistent with correlative imaging, tissue sampling and follow-up. One patient with a suspicious enhancing 2F Bosniak renal cyst had renal cell carcinoma confirmed on biopsy. CONCLUSION: Ferumoxytol-enhanced MRI can increase diagnostic confidence for benign abdominal masses and can increase the conspicuity of mass lesions, relative to unenhanced MRI.

Head-to-Head Comparison of 68Ga-PSMA-11 PET/CT and mpMRI with a Histopathology Gold Standard in the Detection, Intraprostatic Localization, and Determination of Local Extension of Primary Prostate Cancer: Results from a Prospective Single-Center Imaging Trial.

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to multiparametric MRI (mpMRI) in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performance of 68Ga-PSMA-11 PET/CT (PSMA PET/CT), mpMRI, and PSMA PET/CT + mpMRI using 3 independent masked readers for each modality and with histopathology as the gold standard in the detection, intraprostatic localization, and determination of local extension of primary prostate cancer. Methods: Patients with intermediate- or high-risk prostate cancer who underwent PSMA PET/CT as part of a prospective trial (NCT03368547) and mpMRI before radical prostatectomy were included. Each imaging modality was interpreted by 3 independent readers who were unaware of the other modality result. A central majority rule was applied (2:1). Pathologic examination of whole-mount slices was used as the gold standard. Imaging scans and whole-mount slices were interpreted using the same standardized approach on a segment level and a lesion level. A "neighboring" approach was used to define imaging-pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver-operating-characteristic curve analysis. Interreader agreement was calculated using intraclass correlation coefficient analysis. Results: The final analysis included 74 patients (14 [19%] with intermediate risk and 60 [81%] with high risk). The cancer detection rate (lesion-based analysis) was 85%, 83%, and 87% for PSMA PET/CT, mpMRI, and PSMA PET/CT + mpMRI, respectively. The change in AUC was statistically significant between PSMA PET/CT + mpMRI and the 2 imaging modalities alone for delineation of tumor localization (segment-based analysis) (P < 0.001) but not between PSMA PET/CT and mpMRI (P = 0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (P = 0.002) and SVI (P = 0.001). In the segment-level analysis, intraclass correlation coefficient analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range, 0.53-0.64). In the evaluation of T staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusion: PSMA PET/CT and mpMRI have similar accuracy in the detection and intraprostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the coregistration or fusion of PSMA PET/CT and mpMRI (PSMA PET/CT + mpMRI) should be used as it improves tumor extent delineation.

Focal Laser Ablation of Prostate Cancer: An Office Procedure.

In this article, we describe and illustrate an outpatient procedure for focal laser ablation (FLA) of prostate cancer (PCa). The procedure is conceptually similar to a fusion biopsy and is performed under local anesthesia in a clinic setting; treatment time is usually less than one hour. Laser insertion is guided by ultrasound; lesion targeting is via magnetic resonance imaging-ultrasound (MRI/US) fusion, as in targeted prostate biopsy. Real-time ablation monitoring is achieved utilizing a thermal probe adjacent to the laser fiber. The video demonstrates procedure planning, patient preparation, various steps during the procedure, and treatment monitoring. Safety, feasibility, and efficacy of this approach have been established during a previous trial. Outpatient FLA under local anesthesia is an option for management of intermediate risk prostate cancer.

Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings.

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined. RESULTS: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65. CONCLUSIONS: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.

Efficacy of 3T Multiparametric MR Imaging followed by 3T in-Bore MR-Guided Biopsy for Detection of Clinically Significant Prostate Cancer Based on PIRADSv2.1 Score.

PURPOSE: To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). MATERIALS AND METHODS: This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4. RESULTS: 3T IB-MRGB detected PCa and csPCa in 69.1% (262 of 379) and 50.3% (193 of 379) of patients, respectively. The PCa and csPCa detection rates per target were 64.2% (305 of 475) and 43.8% (208 of 475), respectively. The rate of urosepsis, treated with intravenous antibiotics, was 1% (4 patients). In TRUS biopsy negative results and biopsy-naïve subcohorts, csPCa was found in 36.8% (39 of 106) and 52.8% (65 of 123), respectively. In 50.7% (76 of 150) of the active surveillance subcohort, 3T IB-MRGB upgraded the GS assigned in prior TRUS biopsies. Positive predictive values of PIRADSv2.1 categories 3, 4, and 5 for csPCa detection were 24.8%, 44.4%, and 67.1%, respectively. Higher PIRADSv2.1 categories were significantly associated with PCa (odds ratio [OR], 3.97; 95% confidence interval [CI], 2.98-5.28) and csPCa (OR, 1.41; 95% CI, 1.03-1.94) detection. Of 137 PIRADSv2 category 3 lesions, 28 were downgraded to PIRADSv2.1 category 2, in which there were no occurrences of csPCa in histology. CONCLUSIONS: Use of 3T IB-MRGB resulted in detection of csPCa in 50.9% of individuals. 3T IB-MRGB has a high diagnostic yield in individuals with negative TRUS biopsy results and those under active surveillance. The PIRADSv2.1 category is a strong predictor of PCa and csPCa detection.

3-T Multiparametric MRI Followed by In-Bore MR-Guided Biopsy for Detecting Clinically Significant Prostate Cancer After Prior Negative Transrectal Ultrasound-Guided Biopsy.

OBJECTIVE. The purpose of this study was to evaluate the rate of detection of clinically significant prostate cancer (csPCa), as assessed on the basis of Prostate Imaging Reporting and Data System version 2.1 (PI-RADSv2.1) guidelines, using 3-T in-bore MR-guided biopsy (MRGB) for a cohort of patients suspected of having csPCa despite having a history of recent negative transrectal ultrasound-guided biopsy results. MATERIALS AND METHODS. The cohort in this retrospective, single-center study was derived from a database of 330 patients who underwent multiparametric MRI (mpMRI) followed by in-bore transrectal 3-T MRGB. Seventy-nine patients (mean [± SD] age, 64.1 ± 8.6 years) with prior negative transrectal ultrasound-guided biopsy results and positive pre-MRGB mpMRI results (PI-RADS score ≥ 3) composed the final cohort. The rate of detection of PCa and csPCa (the latter of which was defined by a Gleason score of 3 + 4 or higher) was stratified according to updated PI-RADSv2.1 assessment. RESULTS. MRGB detected PCa in 36 patients (45.6%), 30 (83.3%) of whom had csPCa. The PI-RADSv2.1 score was a strong predictor (odds ratio, 3.97; 95% CI, 1.93-7.47) of csPCa detection. We found two benign transition zone target lesions that were downgraded from PI-RADSv2 category 3 to PI-RADSv2.1 category 2. PCa was detected in 18.4% (7/38), 65.2% (15/23), and 87.5% (14/16) of individuals with PI-RADSv2.1 category 3, 4, and 5 lesions, respectively, with 85.7% (6/7), 86.7% (13/15), and 78.6% (11/14) of these cases found to be csPCa, respectively. Of the seven PI-RADSv2.1 category 3 csPCa lesions, six had prostate-specific antigen density greater than 0.10 ng/mL/cc. CONCLUSION. With the use of 3-T in-bore MRGB, csPCa was detected in 38% of individuals with prior negative transrectal ultrasound-guided biopsy results. PI-RADSv2.1 was a strong predictor of csPCa detection. On the basis of our results, patients with PI-RADSv2.1 category 4 or 5 lesions and patients with PI-RADSv2.1 category 3 lesions and a prostate-specific antigen density greater than or equal to 0.10 ng/mL/cc may benefit from in-bore MRGB.

Dynamic contrast-enhanced (DCE) MR imaging: the role of qualitative and quantitative parameters for evaluating prostate tumors stratified by Gleason score and PI-RADS v2.

PURPOSE: To investigate the role of qualitative and quantitative DCE-MRI parameters in prostate cancer (PCa) stratified by whole-mount histopathology (WMHP) Gleason score (GS) and PI-RADSv2. METHODS: This retrospective study included 323 PCa tumors in 254 men, who underwent 3T MRI prior to prostatectomy, 7/2009-12/2016. Qualitative DCE curve types included type 1 (progressive), type 2 (plateau) and type 3 (washout). Quantitative DCE-MRI pharmacokinetic (PK) parameters included Ktrans (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). DCE-MRI features of true positive lesions were evaluated for overall, index, transition zone (TZ) and peripheral zone (PZ), based on GS grade (low = 6, high > 6) and PI-RADSv2 score using SPSSv24. RESULTS: There were 57 (17.6%) low-grade and 266 (82.4%) high-grade PCa lesions. PI-RADSv2 3, 4 and 5 included 106, 120 and 97 lesions, respectively. 251 (77.7%) and 72 (22.3%) lesions were located in PZ and TZ, respectively. High-grade lesions had significantly higher proportion of Type 3 curves compared to low-grade lesions in overall (70.3% vs. 54.4%) and TZ (73.5% vs. 43.5%). As PI-RADSv2 increased, the proportion of type 3 curve significantly increased for overall (80.4-51.9%), index (80.4-54.7%) and PZ (78.7-52.1%) lesions. Among PK parameters, Ktrans (0.43 vs 0.32) and iAUC (8.99 vs 6.9) for overall PCa, Ktrans (0.43 vs 0.31) and iAUC (9 vs 6.67) for PZ PCa, and iAUC (8.94 vs 7.42) for index PCa were significantly higher for high-grade versus low-grade lesions. Also, Ktrans (0.51-0.34), Kep (1.75-1.29) and iAUC (9.79-7.6) for overall PCa, Ktrans (0.53-0.32), Kep (1.81-1.26) and iAUC (9.83-7.34) for PZ PCa; and Kep (1.79-1.17) and iAUC (11.3-8.45) for index PCa increased significantly with a higher PI-RADSv2 score. CONCLUSIONS: The results of study show the possible utility of qualitative and quantitative DCE-MRI parameters for assessment of PCa GS and PI-RADSv2 categorization.

Magnetic Resonance Imaging-Guided Confirmatory Biopsy for Initiating Active Surveillance of Prostate Cancer.

Importance: Transrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance. Objective: To evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance. Design, Settings, and Participants: This retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017. Exposures: All confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment. Main Outcomes and Measures: The primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome. Results: Of 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy. Conclusions and Relevance: The findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.

Utility of Multiparametric MRI for Predicting Residual Clinically Significant Prostate Cancer After Focal Laser Ablation.

OBJECTIVE. The purpose of this study was to compare in a multireader manner the diagnostic accuracies of 3-T multiparametric MRI interpretation and serial prostate-specific antigen (PSA) measurement in predicting the presence of residual clinically significant prostate cancer after focal laser ablation. MATERIALS AND METHODS. Eighteen men had undergone focal laser ablation for low- or intermediate-risk prostate cancer as part of two National Cancer Institute-funded phase 1 clinical trials. Multiparametric MRI was performed immediately after and 6 and 12 months after focal laser ablation. Serial PSA measurements after focal laser ablation were recorded, and MRI-ultrasound fusion biopsy was performed 6 and 12 months after ablation and served as the reference standard. Multiparametric MRI was performed at 3 T with pelvic phased-array coils. T2-weighted, DW, and dynamic contrast-enhanced MR images were retrospectively assessed by two blinded radiologists using a 3-point Likert scale (0-2). Inter-reader agreement was assessed with the Cohen kappa statistic. The diagnostic accuracies of multiparametric MRI and PSA measurement were compared. RESULTS. Residual clinically significant prostate cancer was identified in 11 of 18 (61%) men. Logistic regression analysis of serial PSA measurements yielded a correct classification rate of 61.1% (p > 0.05). Using a multiparametric MRI threshold score of 4 or greater, both radiologists made correct classifications for 16 of 18 men (89%) at 6 months and 15 of 17 men (88%) at 12 months. Interreader agreement was substantial to excellent for T2-weighted imaging, DWI, and dynamic contrast-enhanced MRI and improved uniformly from 6 to 12 months. Logistic regression analysis of the retrospectively reviewed multiparametric MR images yielded AUCs greater than 0.90 for each radiologist 6 and 12 months after focal laser ablation (p < 0.001). CONCLUSION. Multiparametric MRI 6 and 12 months after focal laser ablation significantly outperformed serial PSA measurements for predicting the presence of residual clinically significant prostate cancer.

Comparison of Targeted vs Systematic Prostate Biopsy in Men Who Are Biopsy Naive: The Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) Study.

Importance: Magnetic resonance imaging (MRI) guidance improves the accuracy of prostate biopsy for the detection of clinically significant prostate cancer, but the optimal use of such guidance is not yet clear. Objective: To determine the cancer detection rate (CDR) of targeting MRI-visible lesions vs systematic prostate sampling in the diagnosis of clinically significant prostate cancer in men who were biopsy naive. Design, Setting, and Participants: This paired cohort trial, known as the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study, was conducted in an academic medical center from January 2015 to April 2018. Men undergoing first-time prostate biopsy were enrolled. Paired-cohort participants were a consecutive series of men with MRI-visible lesions (defined by a Prostate Imaging Reporting & Data System version 2 score ≥ 3), who each underwent 3 biopsy methods at the same sitting: first, a systematic biopsy; second, an MRI-lesion biopsy targeted by cognitive fusion; and third, an MRI-lesion targeted by software fusion. Another consecutive series of men without MRI-visible lesions underwent systematic biopsies to help determine the false-negative rate of MRI during the trial period. Main Outcomes and Measures: The primary end point was the detection rate of clinically significant prostate cancer (Gleason grade group ≥2) overall and by each biopsy method separately. The secondary end points were the effects of the Prostate Imaging Reporting & Data System version 2 grade, prostate-specific antigen density, and prostate volume on the primary end point. Tertiary end points were the false-negative rate of MRI and concordance of biopsy-method results by location of detected cancers within the prostate. Results: A total of 300 men participated; 248 had MRI-visible lesions (mean [SD] age, 65.5 [7.7] years; 197 were white [79.4%]), and 52 were control participants (mean [SD] age, 63.6 [5.9] years; 39 were white [75%]). The overall CDR was 70% in the paired cohort group, achieved by combining systematic and targeted biopsy results. The CDR by systematic sampling was 15% in the group without MRI-visible lesions. In the paired-cohort group, CDRs varied from 47% (116 of 248 men) when using cognitive fusion biopsy alone, to approximately 60% when using systematic biopsy (149 of 248 men) or either fusion method alone (154 of 248 men), to 70% (174 of 248 men) when combining systematic and targeted biopsy. Discordance of tumor locations suggests that the different biopsy methods detect different tumors. Thus, combining targeting and systematic sampling provide greatest sensitivity for detection of clinically significant prostate cancer. For all biopsy methods, the Prostate Imaging Reporting & Data System version 2 grade and prostate-specific antigen density were directly associated with CDRs, and prostate volume was inversely associated. Conclusions and Relevance: An MRI-visible lesion in men undergoing first-time prostate biopsy identifies those with a heightened risk of clinically significant prostate cancer. Combining targeted and systematic biopsy offers the best chances of detecting the cancer.

Do contemporary imaging and biopsy techniques reliably identify unilateral prostate cancer? Implications for hemiablation patient selection.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease. RESULTS: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05). CONCLUSIONS: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary.

Utility of Restriction Spectrum Imaging Among Men Undergoing First-Time Biopsy for Suspected Prostate Cancer.

OBJECTIVE. The purpose of this article is to evaluate restriction spectrum imaging (RSI) in men undergoing MRI-ultrasound fusion biopsy for suspected prostate cancer (PCa) and to compare the performance of RSI with that of conventional DWI. MATERIALS AND METHODS. One hundred ninety-eight biopsy-naïve men enrolled in a concurrent prospective clinical trial evaluating MRI-targeted prostate biopsy underwent multiparametric MRI with RSI. Clinical and imaging features were compared between men with and without clinically significant (CS) PCa (MRI-ultrasound fusion biopsy Gleason score ≥ 3 + 4). RSI z score and apparent diffusion coefficient (ADC) were correlated, and their diagnostic performances were compared. RESULTS. CS PCa was detected in 109 of 198 men (55%). Using predefined thresholds of ADC less than or equal to 1000 µm2/s and RSI z score greater than or equal to 3, sensitivity and specificity for CS PCa were 86% and 38%, respectively, for ADC and 61% and 70%, respectively, for RSI. In the transition zone (n = 69), the sensitivity and specificity were 94% and 17%, respectively, for ADC and 59% and 69%, respectively, for RSI. Among lesions with CS PCa, RSI z score and ADC were significantly inversely correlated in the peripheral zone (ρ = -0.4852; p < 0.01) but not the transition zone (ρ = -0.2412; p = 0.17). Overall diagnostic accuracies of RSI and DWI were 0.70 and 0.68, respectively (p = 0.74). CONCLUSION. RSI and DWI achieved equivalent diagnostic performance for PCa detection in a large population of men undergoing first-time prostate biopsy for suspected PCa, but RSI had superior specificity for transition zone lesions.

Cancer core length from targeted biopsy: an index of prostate cancer volume and pathological stage.

OBJECTIVE: To study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)-visible index lesions, to volume of that tumour found at radical prostatectomy (RP). PATIENTS AND METHODS: In all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an index MRI-visible lesion (TB) and 69 in whom MCCL came from a non-targeted lesion (non-targeted biopsy [NTB]). MRI was 3-T multi-parametric and biopsy was via MRI-ultrasonography fusion. RESULTS: In the TB group, MCCL correlated with volume of clinically significant index tumours (ρ = 0.44-0.60, P < 0.01). The correlation was similar for first and repeat biopsy and for transition and peripheral zone lesions (ρ = 0.42-0.49, P < 0.01). No correlations were found in the NTB group. TB MCCL (6-10 and >10 mm) and MRI lesion diameter (>20 mm) were independently associated with tumour volume. TB MCCLs >10 mm and Gleason scores >7 were each associated with pathological T3 disease (odds ratios 5.73 and 5.04, respectively), but MRI lesion diameter lesion was not. CONCLUSIONS: MCCL on a TB from an MRI-visible lesion is an independent predictor of both cancer volume and pathological stage. This relationship does not exist for MCCL from a NTB core. Quantifying CCL on MRI-TBs may have a value, not previously described, to risk-stratify patients with prostate cancer before treatment.

Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.

Use of MRI-Guided Biopsy for Selection and Follow-up of Men Undergoing Hemi-gland Cryoablation of Prostate Cancer.

OBJECTIVE: To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy. METHODS: Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life. RESULTS: Cryotherapy was completed satisfactorily in all 29 cases in <60 minutes with no intraoperative complications. Significant decreases in PSA (median decrease 5.6 ng/mL) and PSA density (median decrease 0.14 ng/mL/cc) were observed (P < .01). At 6 months, 23 patients (79%) demonstrated no residual cancer on follow-up MRI-guided biopsy of the treated side. Three patients (10%) revealed micro-residual disease. Three patients (10%) had residual cancer and underwent further treatment. Ipsilateral MRI lesions were present before treatment in 26 patients and after treatment in only 2, reflecting the gross ablative effect; however, MRI showed disappearance of lesions in 4 patients with residual tumor on biopsy. The single complication was 1 case of transient urinary retention; 85% of men who were sexually active continued without change after treatment. Voiding function was unchanged. CONCLUSION: Hemi-gland cryoablation for clinically-significant CaP is well-tolerated, and when patients are selected and followed by MRI/US fusion biopsy, cancer control appears promising at 6 months.

Three Tesla Multiparametric Magnetic Resonance Imaging: Comparison of Performance with and without Endorectal Coil for Prostate Cancer Detection, PI-RADS™ version 2 Category and Staging with Whole Mount Histopathology Correlation.

PURPOSE: We investigated the performance of 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil to detect prostate cancer with a whole mount histopathology reference. MATERIALS AND METHODS: This retrospective HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, case-control study included patients who underwent 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil from July 2009 to December 2016 prior to prostatectomy. The tumor detection rate was calculated for total and index lesions. Lesion magnetic resonance imaging and histopathology features were compared between the 2 groups. Using SPSS®, version 24 p <0.05 was considered significant. RESULTS: A total of 871 whole mount histopathology lesions in 429 patients with a mean ± SD age of 61.8 ± 7 years were included in analysis. The subcohorts with and without an endorectal coil comprised 260 and 169 patients with a total of 529 and 342 lesions, respectively. The overall tumor detection rates in all patients, and in the endorectal coil and nonendorectal coil subcohorts were 49.6% (432 of 871 patients), 50.5% (267 of 529) and 48.2% (165 of 342), respectively. The index tumor detection rates overall, and in the endorectal coil and nonendorectal coil subcohorts were 77.6% (333 of 429 patients), 78.5% (204 of 260) and 76.3% (129 of 169), respectively. In the endorectal coil and nonendorectal coil subcohorts we detected 35.9% (66 of 184) and 48.4% (76 of 157) of anterior lesions (p = 0.019), 58% (200 of 345) and 48.1% (89 of 185) of posterior lesions (p = 0.025), 37.3% (41 of 110) and 54.4% (62 of 114) of transition zone lesions (p = 0.010), and 53.7% (225 of 419) and 45.2% (103 of 228) of peripheral lesions (p = 0.033), respectively. After adjusting for clinical and pathological factors the endorectal coil group only showed higher detection of peripheral and posterior prostate cancer. CONCLUSIONS: We found that 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil had similar detection of overall and index prostate cancer. However, the endorectal coil subcohort had significantly higher detection of posterior and peripheral prostate cancer, and lower detection of anterior and transition zone prostate cancer.