Prostate magnetic resonance imaging-targeted biopsy global grade correlates better than highest grade with prostatectomy grade.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS: We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS: Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS: When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

Stimulated Raman histology, a novel method to allow for rapid pathologic examination of unprocessed, fresh prostate biopsies.

INTRODUCTION: Delay between targeted prostate biopsy (PB) and pathologic diagnosis can lead to a concern of inadequate sampling and repeated biopsy. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real-time, label-free, high-resolution microscopic images of unprocessed, unsectioned tissue. This technology holds potential to decrease the time for PB diagnosis from days to minutes. We evaluated the concordance of pathologist interpretation of PB SRH as compared with traditional hematoxylin and eosin (H&E) stained slides. METHODS: Men undergoing prostatectomy were included in an IRB-approved prospective study. Ex vivo 18-gauge PB cores, taken from prostatectomy specimen, were scanned in an SRH microscope (NIO; Invenio Imaging) at 20 microns depth using two Raman shifts: 2845 and 2930 cm-1 , to create SRH images. The cores were then processed as per normal pathologic protocols. Sixteen PB containing a mix of benign and malignant histology were used as an SRH training cohort for four genitourinary pathologists, who were then tested on a set of 32 PBs imaged by SRH and processed by traditional H&E. Sensitivity, specificity, accuracy, and concordance for prostate cancer (PCa) detection on SRH relative to H&E were assessed. RESULTS: The mean pathologist accuracy for the identification of any PCa on PB SRH was 95.7%. In identifying any PCa or ISUP grade group 2-5 PCa, a pathologist was independently able to achieve good and very good concordance (κ: 0.769 and 0.845, respectively; p < 0.001). After individual assessment was completed a pathology consensus conference was held for the interpretation of the PB SRH; after the consensus conference the pathologists' concordance in identifying any PCa was also very good (κ: 0.925, p < 0.001; sensitivity 95.6%; specificity 100%). CONCLUSION: SRH produces high-quality microscopic images that allow for accurate identification of PCa in real-time without need for sectioning or tissue processing. The pathologist performance improved through progressive training, showing that ultimately high accuracy can be obtained. Ongoing SRH evaluation in the diagnostic and treatment setting hold promise to reduce time to tissue diagnosis, while interpretation by convolutional neural network may further improve diagnostic characteristics and broaden use.

Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

BACKGROUND: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: HGPCa are highly infiltrated by exhausted CD8+ T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8+ T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8+  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8+  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8+  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS: Our study reveals a suppressive TME with high levels of CD8+ T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice.

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

Followup of Men with PI-RADS™ 4 or 5 Abnormality on Prostate Magnetic Resonance Imaging and Nonmalignant Pathological Findings on Initial Targeted Prostate Biopsy.

PURPOSE: A benign magnetic resonance imaging targeted prostate biopsy in the setting of a PI-RADS™ 4/5 abnormality presents a clinical dilemma for future management. We evaluated benign histological features on magnetic resonance imaging targeted prostate biopsy to determine if they predict the likelihood of missed cancer on subsequent biopsy. MATERIALS AND METHODS: Between June 2012 and September 2016, 1,595 men were enrolled in a prospective study of magnetic resonance imaging targeted and systematic biopsy outcomes. We re-reviewed pathology from benign biopsies of PI-RADS 4/5 abnormalities and divided them into 5 groups for comparison to outcomes of clinical followup: inflammation (38%), stroma/glandular hyperplasia (9%), normal prostate tissue (28%), atypical small acinar proliferation/high grade prostatic intraepithelial neoplasia (9%) and cancer in adjacent systematic cores (16%). RESULTS: Of 497 men 88 (18%) with PI-RADS 4/5 abnormality prior to initial biopsy had no cancer on magnetic resonance imaging targeted prostate biopsy. On followup, 45 men underwent repeat magnetic resonance imaging: 12 (27%) had persistent PI-RADS 4/5 abnormalities, 17 (38%) had PI-RADS 2/3, 16 (35%) had PI-RADS 1. On repeat magnetic resonance imaging targeted prostate biopsy, cancer was found in 62.5% of men with PI-RADS 4/5 and 23% of men with PI-RADS 2/3. Histological groups on initial biopsy were not predictive of the likelihood of PI-RADS downgrade on repeat magnetic resonance imaging or cancer detection on repeat biopsy. CONCLUSIONS: Among men with no cancer on magnetic resonance imaging targeted prostate biopsy performed for PI-RADS abnormality, downgrade of PI-RADS score is noted in 73% on repeat magnetic resonance imaging. Persistence of PI-RADS 4/5 predicts a higher risk of missed cancer, warranting prompt re-biopsy. While histological findings such as inflammation may underlie some PI-RADS 4/5 abnormalities, initial histology is a poor predictor of cancer likelihood on repeat biopsy.

Application of the PRECISION Trial Biopsy Strategy to a Contemporary Magnetic Resonance Imaging-Targeted Biopsy Cohort-How Many Clinically Significant Prostate Cancers are Missed?

PURPOSE: To demonstrate the generalizability of PRECISION findings and apply the PRECISION biopsy strategy to a contemporary cohort to characterize cancers missed by employing this strategy. MATERIALS AND METHODS: A total of 629 men biopsied between February 2015 and September 2018 met PRECISION inclusion criteria. Men with PI-RADS™ 1-2 magnetic resonance imaging were only biopsied if high clinical suspicion for cancer. Missed cancers were defined as prostate cancer identified uniquely on systematic biopsy in men with PI-RADS 3-5 magnetic resonance imaging, or on either systematic biopsy or magnetic resonance imaging-targeted prostate biopsy in men with PI-RADS 1-2 magnetic resonance imaging. Outcomes included 1) clinically significant prostate cancer, Gleason grade group 2 or greater, detection rate, 2) missed clinically significant prostate cancer rate upon application of PRECISION biopsy strategy, 3) Gleason grade group distribution, core size, spatial orientation and oncologic risk among missed cancers. RESULTS: Application of the PRECISION biopsy strategy to the study cohort resulted in avoidance of biopsy in 28%, similar magnetic resonance imaging-targeted prostate biopsy detection rate to PRECISION, reduction of Gleason grade group 1 detection rate by 60% and reduction of clinically significant prostate cancer detection rate by 19%. Missed clinically significant prostate cancers were often smaller than 6 mm (54.5%), Gleason grade group 2 (67.3%) and low risk by clinical nomogram (74.6%). Gleason grade group 1 cancers identified uniquely on systematic biopsy were often contralateral to magnetic resonance imaging target (46.4%), while missed clinically significant prostate cancer was predominantly ipsilateral (81%). Limitations include biopsy of only men with high risk clinical features among PI-RADS 1-2 magnetic resonance imaging, potentially overestimating the clinically significant prostate cancer detection rate. CONCLUSIONS: The study cohort demonstrated generalizability of PRECISION findings. Applying the PRECISION biopsy strategy greatly reduces Gleason grade group 1 detection rate, while missing a small number of clinically significant prostate cancer, typically small volume, low risk, and Gleason grade group 2. Missed clinically significant prostate cancer is predominantly ipsilateral to magnetic resonance imaging target, possibly representing targeting error.

MRI predicts prostatic urethral involvement in men undergoing radical prostatectomy: implications for cryo-ablation of localized prostate cancer.

PURPOSE: To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. METHODS: Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. RESULTS: Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. CONCLUSIONS: Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

DHX15 is up-regulated in castration-resistant prostate cancer and required for androgen receptor sensitivity to low DHT concentrations.

BACKGROUND: DHX15 is a member of the DEAH-box (DHX) RNA helicase family. Our previous study identified it as an AR coactivator which contributes to prostate cancer progression. METHODS: We investigated DHX15 expression in castration resistant prostate cancer specimens and the influence of DHX15 on the responsiveness of prostate cancer cells to DHT stimulation. We also explored the role DHX15 played in enzalutamide resistance and the interacting domain in DHX15 with AR. DHX15 expression level in human CRPC specimens and prostate cancer specimens was detected by tissue microarray (TMA) immunostaining analysis. Colony formation assay was performed to determine the proliferation of cells treated with enzalutamide or DHT. siRNAs were used to knockdown DHX15. The interactions between DHX15 and AR were detected using co-immunoprecipitation assay. RESULTS: The expression level of DHX15 was upregulated in human CRPC specimens compared with hormone naïve prostate cancer specimens. DHX15 knockdown reduced AR sensitivity to low DHT concentrations in C4-2 cells. Inactivation of DHX15 sensitizes the enzalutamide treatment in C4-2 cells. Deletion mutagenesis indicated that DHX1 5 interacts with AR through its N terminal domain. CONCLUSIONS: These findings suggest that DHX15 contributes to prostate cancer progression. DHX15 is required for androgen receptor sensitivity to low DHT concentrations and contributes to enzalutamide resistance in C4-2 cells. Targeting DHX15 may improve the ADT treatment.

The Institutional Learning Curve of Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy: Temporal Improvements in Cancer Detection in 4 Years.

PURPOSE: While magnetic resonance imaging-ultrasound fusion targeted biopsy allows for improved detection of clinically significant prostate cancer, a concerning amount of clinically significant disease is still missed. We hypothesized that a number of these misses are due to the learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. We report the results of repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer and the institutional learning curve in the detection of clinically significant prostate cancer with time. MATERIALS AND METHODS: We analyzed the records of 1,813 prostate biopsies in a prospectively acquired cohort of men who presented for prostate biopsy in a 4-year period. All men were offered prebiopsy magnetic resonance imaging and were assigned a maximum PI-RADS™ (Prostate Imaging Reporting and Data System version 2) score. Biopsy outcomes in men with a suspicious region of interest were compared. The relationship between time and clinically significant prostate cancer detection was analyzed. RESULTS: The clinically significant prostate cancer detection rate increased 26% with time in men with a PI-RADS 4/5 region of interest. On repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer 53% of those with a PI-RADS 4/5 region of interest demonstrated clinically significant discordance from the initial magnetic resonance imaging-ultrasound fusion targeted biopsy compared to only 23% with a PI-RADS 1/2 region of interest. Significantly less clinically significant prostate cancer was missed or under graded in the most recent biopsies compared to the earliest biopsies. CONCLUSIONS: The high upgrade rate on repeat magnetic resonance imaging-ultrasound fusion targeted biopsy and the increasing cancer detection rate with time show the significant learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. Men with low risk or negative biopsies with a persistent, concerning region of interest should be promptly rebiopsied. Improved targeting accuracy with operator experience can help decrease the number of missed cases of clinically significant prostate cancer.

Multiparametric magnetic resonance imaging identifies significant apical prostate cancers.

OBJECTIVE: To determine if multiparametric (mp) magnetic resonance imaging (MRI) can identify significant apical disease, thereby informing decisions regarding preservation of the membranous urethra. MATERIALS AND METHODS: Men undergoing radical prostatectomy (RP) between January 2012 and June 2016, who underwent a 12-core transrectal ultrasonography-guided systematic biopsy (SB), preoperative 3-Tesla MRI, and sectioning of the prostate specimen with tumour foci mapping, were extracted from a single surgeon's prospective longitudinal outcomes database. Apical SB and mpMRI lesion results were compared with regard to their ability to predict aggressive tumours in the prostatic apex (PA), defined as prostate cancer grade group >1. RESULTS: Of the 100 men who met the eligibility criteria, 43 (43%) exhibited aggressive prostate cancer in the distal 5 mm of the apex. A Likert score >2 in the apical one-third of the prostate was found to be more reliable than any cancer found on apical SB at detecting aggressive cancer in the apex. On multivariate regression analysis, which included Likert score in the apex, age, prostate-specific antigen (PSA) level, prostate size and presence of any cancer on apical biopsy, only Likert score (P = 0.005) and PSA level (P = 0.025) were significant and independent predictors of aggressive cancer in the distal apex. CONCLUSION: The results of the study showed that MRI was superior to SB at identifying aggressive prostate cancer within the distal PA and may be useful for planning the extent of apical preservation during RP.

Visual Assessment of the Intensity and Pattern of T1 Hyperintensity on MRI to Differentiate Hemorrhagic Renal Cysts From Renal Cell Carcinoma.

OBJECTIVE: The purpose of this study was to apply a visual assessment of the intensity and pattern of T1 hyperintensity at MRI to differentiate hemorrhagic renal cysts from renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 144 T1-hyperintense renal lesions (62 cysts, all showing no enhancement on subtracted contrast-enhanced images and either 2-year stability or unenhanced CT density > 70 HU, and 82 histologically confirmed RCCs) in 144 patients were included. Two radiologists independently characterized qualitative features of the T1 hyperintensity in each lesion on unenhanced T1-weighted images. An additional radiologist placed ROIs to measure lesions' T1 signal intensity normalized to that of the psoas muscle. Chi-square and unpaired t tests were performed to compare the pattern of T1 hyperintensity between groups. RESULTS: The T1 hyperintensity was considered marked in 62.9% of cysts and 17.1% of RCCs for reader 1 and in 46.8% of cysts and 8.5% of RCCs for reader 2 (p < 0.001). The T1 hyperintensity exhibited a diffusely homogeneous distribution in 88.7% of cysts and 7.3% of RCCs for reader 1 and in 72.6% of cysts and 4.9% of RCCs for reader 2 (p < 0.001). The combination of both diffusely homogeneous distribution and marked degree of T1 hyperintensity achieved sensitivities of 40.3-56.5%, specificities of 97.6-98.8%, and accuracies of 73.6-79.9% for the diagnosis of T1-hyperintense cysts. The two cases of RCC exhibiting this imaging pattern for at least one reader were both papillary RCCs. Normalized signal intensity was 2.39 ± 0.99 in T1-hyperintense cysts versus 2.12 ± 0.84 in T1-hyperintense RCCs (p = 0.088). CONCLUSION: Diffuse T1 hyperintensity, particularly when marked, strongly indicates a hemorrhagic cyst rather than an RCC. Deferral of follow-up imaging may be considered when this imaging appearance is encountered at unenhanced MRI.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

OBJECTIVE: Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. METHODS: This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. RESULTS: From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. CONCLUSION: The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. ABBREVIATIONS: AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

Likert score 3 prostate lesions: Association between whole-lesion ADC metrics and pathologic findings at MRI/ultrasound fusion targeted biopsy.

BACKGROUND: To assess associations between whole-lesion apparent diffusion coefficient (ADC) metrics and pathologic findings of Likert score 3 prostate lesions at MRI/ultrasound fusion targeted biopsy. METHODS: This retrospective Institutional Review Board-approved study received a waiver of consent. We identified patients receiving a highest lesion score of 3 on 3 Tesla multiparametric MRI reviewed by a single experienced radiologist using a 5-point Likert scale and who underwent fusion biopsy. A total of 188 score 3 lesions in 158 patients were included. Three-dimensional volumes-of-interest encompassing each lesion were traced on ADC maps. Logistic regression was used to predict biopsy results based on whole-lesion ADC metrics and patient biopsy history. Biopsy yield was compared between metrics. RESULTS: By lesion, targeted biopsy identified tumor in 22.3% and Gleason score (GS) > 6 tumor in 8.5%, although results varied by biopsy history: biopsy-naïve (n = 80), 20.0%/8.8%; prior negative biopsy (n = 53), 9.4%/1.9%; prior positive biopsy (n = 55): 40.0%/14.5%. Biopsy history, whole-lesion mean ADC, whole-lesion ADC10-25 , and whole-lesion ADC25-50 were each significantly associated with tumor or GS > 6 tumor at fusion biopsy (P ≤ 0.047). In men without prior negative prostate biopsy, whole-lesion ADC25-50 ≤ 1.04*10(-3) mm2 /s achieved 90.0% sensitivity and 50.0% specificity for GS > 6 tumor, which was significantly higher (P < 0.001) than specificity of PSA (17.5%) at identical sensitivity. CONCLUSION: For score 3 lesions in patients without prior negative biopsy, whole-lesion ADC metrics help detect GS > 6 cancer while avoiding negative biopsies. However, deferral of fusion biopsy may be considered for score 3 lesions in patients with prior negative biopsy (without applying whole-lesion ADC metrics) given exceedingly low (∼ 2%) frequency of GS > 6 tumor in this group.

Incidence of intraductal carcinoma, multifocality and bilateral significant disease in radical prostatectomy specimens from Japan and United States.

Significant differences, including epidemiologic, clinical, pathologic and genetic, exist between Asian and Caucasian prostate cancer. Detailed pathologic data are, however, scarce. We studied in detail and compared the pathological features of prostate cancer in radical prostatectomy specimens in 228 patients (117 Japan, 111 US). Japanese prostate cancer had a higher Gleason grade group (mean 2.67 vs. 2.42 US, P < 0.05), but lower pathological stage (72 % pT2 and 28 % pT3 vs 55 % pT2 and 45 % pT3 US, P < 0.05). Japanese cancer showed significantly more tumor foci (3.8 vs 2.9 US, P < 0.05), and higher incidence of bilateral significant disease (81.3 % vs. 66.7 % US, P < 0.05). The dominant tumor nodules in Japanese cases had higher Gleason grade group (mean 2.73 vs. 2.40 US, P < 0.05). The incidence of intraductal carcinoma was significantly higher in Japanese patients (35.3 % vs. 12.6 % US, P < 0.01), which was independent of Gleason score (7: 30.9 % Japan vs 11.8 % US, P < 0.01; ≥ 8: 87.5 % Japan vs 28.6 % US, P < 0.01) and tumor stage (pT2: 24.1 % Japan vs 6.6 % US, P < 0.01; pT3: 62.9 % Japan vs 20 % US, P < 0.01). These findings demonstrate distinct pathological features in prostate cancer between Japanese and Caucasian patients, and may have important diagnostic and therapeutic implications.

Investigation of Multisequence Magnetic Resonance Imaging for Detection of Recurrent Tumor After Transurethral Resection for Bladder Cancer.

PURPOSE: The aim of this study was to evaluate multisequence magnetic resonance imaging (MRI) in detecting local recurrence after transurethral resection for bladder cancer. METHODS: Thirty-six patients with bladder cancer with previous transurethral resection underwent bladder MRI incorporating T2-weighted imaging, diffusion-weighted imaging, and delayed contrast-enhanced T1-weighted imaging, followed by cystoscopy. Two radiologists (R1 and R2) evaluated examinations for suspicious findings. RESULTS: Forty-seven percent of patients had recurrent tumor at cystoscopy and biopsy. Using multisequence MRI, sensitivity and specificity were 67% and 81% for R1 and 73% and 62% for R2. Both readers missed 1 high-grade pathologic stage T1 recurrent tumor; otherwise, all missed tumors were low-grade pathologic stage Ta lesions. All false positives for R1 and 7 of 9 false positives for R2 were in patients receiving previous bacillus Calmette-Guerin therapy. Furthermore, 40% to 50% of solitary abnormalities and 83% to 100% of multifocal abnormalities were tumor recurrences; 12% to 20% of smooth wall thickening, 50% to 75% of irregular wall thickening, and 88% to 100% of papillary masses were tumor recurrences. CONCLUSIONS: Although multisequence MRI exhibited moderate performance for detecting recurrent tumor, nearly all missed tumors were low grade and noninvasive.

Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.

PURPOSE: We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. MATERIALS AND METHODS: Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. RESULTS: Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. CONCLUSIONS: Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy.

Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification.

PURPOSE: MRF-TB (magnetic resonance imaging-ultrasound fusion targeted prostate biopsy) may improve the detection of prostate cancer in men presenting for prostate biopsy. We report clinical outcomes of 12-core systematic biopsy and MRF-TB in men who presented for primary biopsy and further describe pathological characteristics of cancers detected by systematic biopsy and not by MRF-TB. MATERIALS AND METHODS: Clinical outcomes of 452 consecutive men who underwent prebiopsy multiparametric magnetic resonance imaging followed by MRF-TB and systematic biopsy at our institution between June 2012 and June 2015 were captured in an institutional review board approved database. Clinical characteristics, biopsy results and magnetic resonance imaging suspicion scores were queried from the database. RESULTS: Prostate cancer was detected in 207 of 382 men (54.2%) with a mean±SD age of 64±8.5 years and mean±SEM prostate specific antigen 6.8±0.3 ng/ml who met study inclusion criteria. The cancer detection rate of systematic biopsy and MRF-TB was 49.2% and 43.5%, respectively (p=0.006). MRF-TB detected more Gleason score 7 or greater cancers than systematic biopsy (117 of 132 or 88.6% vs 102 of 132 or 77.3%, p=0.037). Of 41 cancers detected by systematic biopsy but not by MRF-TB 34 (82.9%) demonstrated Gleason 6 disease, and 26 (63.4%) and 34 (82.9%) were clinically insignificant by Epstein criteria and a UCSF CAPRA (University of California-San Francisco-Cancer of the Prostate Risk Assessment) score of 2 or less, respectively. CONCLUSIONS: In men presenting for primary prostate biopsy MRF-TB detects more high grade cancers than systematic biopsy. Most cancers detected by systematic biopsy and not by MRF-TB are at clinically low risk. Prebiopsy magnetic resonance imaging followed by MRF-TB decreases the detection of low risk cancers while significantly improving the detection and risk stratification of high grade disease.

Whole-lesion apparent diffusion coefficient metrics as a marker of percentage Gleason 4 component within Gleason 7 prostate cancer at radical prostatectomy.

PURPOSE: To retrospectively assess the utility of whole-lesion apparent diffusion coefficient (ADC) metrics in characterizing the Gleason 4 component of Gleason 7 prostate cancer (PCa) at radical prostatectomy. MATERIALS AND METHODS: Seventy patients underwent phased-array coil 3T-magnetic resonance imaging (MRI) before prostatectomy. A uropathologist mapped locations and Gleason 4 percentage (G4%) of Gleason 7 tumors. Two radiologists independently reviewed ADC maps, aware of tumor locations but not G4%, and placed a volume-of-interest (VOI) on all slices including each lesion on the ADC map to obtain whole-lesion mean ADC and ADC entropy. Entropy reflects textural variation and increases with greater macroscopic heterogeneity. Performance for characterizing Gleason 7 tumors was assessed with mixed-model analysis of variance (ANOVA) and logistic regression. RESULTS: Among 84 Gleason 7 tumors (G4% 5%-85%, median 30%; 59 Gleason 3+4, 25 Gleason 4+3), ADC entropy was significantly higher in Gleason 4+3 than Gleason 3+4 tumors (R1: 5.27 ± 0.61 vs. 4.62 ± 0.78, P = 0.001; R2: 5.91 ± 0.32 vs. 5.57 ± 0.56, P = 0.004); mean ADC was not significantly different between these groups (R1: 0.90 ± 0.15*10(-3) cm(2) /s vs. 0.98 ± 0.21*10(-3) cm(2) /s, P = 0.075; R2: 1.06 ± 0.19*10(-3) cm(2) /s vs. 1.14 ± 0.16*10(-3) cm(2) /s, P = 0.083). The area under the receiver operating characteristic (ROC) curve (AUC) for differentiating groups was significantly higher with ADC entropy than mean ADC for one observer (R1: 0.74 vs. 0.57, P = 0.027; R2: 0.69 vs. 0.61, P = 0.329). For R1, correlation with G4% was moderate for ADC entropy (r = 0.45) and weak for mean ADC (r = -0.25). For R2, correlation with G4% was moderate for ADC entropy (r = 0.41) and mean ADC (r = -0.32). For both readers, ADC entropy (P = 0.028-0.003), but not mean ADC (P = 0.384-0.854), was a significant independent predictor of G4%. CONCLUSION: Whole-lesion ADC entropy outperformed mean ADC in characterizing Gleason 7 tumors and may help refine prognosis for this heterogeneous PCa subset.

T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.

PURPOSE: To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. MATERIALS AND METHODS: Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. RESULTS: Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. CONCLUSION: We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T.