Pooria Khoshnoodi

Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use of Patient Specific Molds to Correlate Images with Whole Mount Pathology

Purpose: We evaluated the accuracy of magnetic resonance imaging in determining the size and shape of localized prostate cancer. Materials and Methods: The subjects were 114 men who underwent multiparametric magnetic resonance imaging before radical prostatectomy with patient specific mold processing of the specimen from 2013 to 2015. T2‐weighted images were used to contour the prostate capsule and cancer suspicious regions of interest. The contours were used to design and print 3‐dimensional custom molds, which permitted alignment of excised prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3 dimensions from digitized whole mount sections. Tumors were then matched with regions of interest and the relative geometries were compared. Results: Of the 222 tumors evident on whole mount sections 118 had been identified on magnetic resonance imaging. For the 118 regions of interest mean volume was 0.8 cc and the longest 3‐dimensional diameter was 17 mm. However, for matched pathological tumors, of which most were Gleason score 3 + 4 or greater, mean volume was 2.5 cc and the longest 3‐dimensional diameter was 28 mm. The median tumor had a 13.5 mm maximal extent beyond the magnetic resonance imaging contour and 80% of cancer volume from matched tumors was outside region of interest boundaries. Size estimation was most accurate in the axial plane and least accurate along the base‐apex axis. Conclusions: Magnetic resonance imaging consistently underestimates the size and extent of prostate tumors. Prostate cancer foci had an average diameter 11 mm longer and a volume 3 times greater than T2‐weighted magnetic resonance imaging segmentations. These results may have important implications for the assessment and treatment of prostate cancer.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2–based Diagnostic Performance for Detection of Prostate Cancer

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10-6 mm2/sec vs 1111 × 10-6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3-5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2. ©RSNA, 2016.

Semimembranosus tendon avulsion fracture of the posteromedial tibial plateau associated with posterior cruciate ligament tear and capsular rupture

Semimembranosus tendon avulsion fractures are an uncommon occurrence and are often associated with anterior cruciate ligament (ACL) and medial meniscus tears. We present the imaging features of an unusual case of semimembranosus avulsion fracture of the posteromedial tibial plateau associated with posterior cruciate ligament (PCL) tear, medial meniscus tear, and capsular rupture in a 26-year-old man with a football injury.

A 17-Gene Genomic Prostate Score Assay Provides Independent Information on Adverse Pathology in the Setting of Combined Multiparametric Magnetic Resonance Imaging Fusion Targeted and Systematic Prostate Biopsy

Purpose: Multiparametric magnetic resonance imaging and biopsy based molecular tests such as the 17‐gene Oncotype DX® Genomic Prostate Score™ assay are increasingly performed to improve risk stratification in men with clinically localized prostate cancer. The prostate score assay was previously shown to be a significant independent predictor of adverse pathology findings at radical prostatectomy in men diagnosed by systematic biopsies only. Therefore, we investigated the ability of the prostate score assay to predict adverse pathology findings in the setting of magnetic resonance imaging guided prostate biopsy. Materials and Methods: We identified men diagnosed with NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate risk prostate cancer who underwent simultaneous multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy with subsequent radical prostatectomy within 6 months. Prostate score assay testing was performed on biopsy tissue with the highest Gleason score. The primary outcome of the study was adverse pathology findings, defined as Gleason score 4 + 3 or greater disease and/or pT3+ at radical prostatectomy. Independent predictors of adverse pathology findings were determined in a multivariable model to adjust for clinical parameters. Results: A total of 134 men were eligible for primary analysis. On univariable analysis the UCLA score, magnetic resonance imaging, prostate score assay results and biopsy Gleason score were significant predictors of adverse pathology findings. After multivariable adjustment prostate score assay values remained a significant predictor of adverse pathology results (prostate score assay per 20 U OR 3.28, 95% CI 1.74–6.62, p <0.001). A wide and overlapping distribution of prostate score assay results was seen across PI‐RADS® (Prostate Imaging Reporting and Data System) version 2 scores. Conclusions: The prostate score assay result is an independent predictor of adverse pathology findings in patients who were diagnosed with very low, low or intermediate risk prostate cancer in the setting of multiparametric magnetic resonance imaging fusion prostate biopsy. This assay can be useful as an independent technology or an adjunct technology to multiparametric magnetic resonance imaging to individualize risk stratification of low and intermediate risk prostate cancer.

3T Multiparametric MRI: Comparison of Performance With and Without Endorectal Coil for Prostate Cancer Detection, PI-RADSv2 Category and Staging with Whole Mount Histopathology Correlation in 429 Patients

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.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.

A system using patient-specific 3D-printed molds to spatially align in vivo MRI with ex vivo MRI and whole-mount histopathology for prostate cancer research: System to Align Prostate MRI With Histopathology

Patient‐specific 3D‐printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole‐mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated.

Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate

PurposeWe present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer.Materials and methodsIn our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space.ResultsProbabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate.ConclusionWe present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

3T multiparametric MR imaging, PIRADSv2-based detection of index prostate cancer lesions in the transition zone and the peripheral zone using whole mount histopathology as reference standard

PurposeTo evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount histopathology correlation.MethodsAn institution review board-approved, HIPAA-compliant single-arm observational study of 425 consecutive men with 3T mpMRI prior to radical prostatectomy from December 2009 to October 2016 was performed. A genitourinary radiologist and a genitourinary pathologist matched all lesions detected on whole mount histopathology with lesions concordant for size and location on 3T mpMRI. Differences in clinical, MRI parameters, and histopathology between transition zone and peripheral zone were determined and analyzed with χ2 and Mann–Whitney U test. AUC was measured.Results3T mpMRI detected 248/323 (76.7%) index lesions in peripheral zone and 75/323 (23.2%) in transition zone. Transition zone prostate cancer had higher median prostate-specific antigen (p = 0.001), larger tumor on 3T mpMRI (p = 0.001), lower proportions of PI-RADSv2 category 4 and 5 (p < 0.001), and lower pathological stage (p = 0.055) compared to peripheral zone prostate cancer. No significant differences were detected in prostate-specific antigen density, preoperative biopsy, and pathology Gleason Scores. After adjusting for significant variables from univariate analysis including prostate volume, tumor volume, prostate-specific antigen, PI-RADSv2 category, AUC for predicting clinically significant tumor in transition zone and peripheral zone were 0.80 and 0.72, respectively (p = 0.36).ConclusionsThe diagnostic performance of PI-RADSv2 for clinically significant transition and peripheral zone prostate cancer was similar. However, there was a lower portion of PI-RADSv2 4 and 5 lesions in transition zone compared to peripheral zone.

MP38-11 PROSTATE CANCER VOLUME ON 3-TESLA MULTIPARAMETRIC DIFFERENT SEQUENCES: CORRELATED AND VERIFIED ON WHOLE MOUNT HISTOPATHOLOGY SECTIONED WITH 3D-PRINTED CUSTOM-DESIGNED MOLDS

INTRODUCTION AND OBJECTIVES: Transperineal template mapping MRI/TRUS fusion biopsy (TMBx) offers superior accuracy and allows optimal risk stratification for patients detected with prostate cancer. However, limited data is available regarding complications and morbidity following TMBx. The goal of this retrospective analysis was to obtain the complication rate follwing TMBx in a large series. METHODS: The records of 402 consecutive patients undergoing TMBx between June 2013 and August 2016 were reviewed. All patients received a single shot antibiotic prophylaxis with 80 mg gentamicin. All underwent transperineal fusion targeted biopsy of MRIsuspicious lesions (median 3 cores per lesion) and transperineal extended template biopsy (median 41 cores). The complications were reported according to the modified Clavien-Dindo classification system. RESULTS: Of the 421 biopsies, 371 (88.1%) had an uneventful biopsywithout complications. Twenty patients (4.8%) showedpost-biopsy complications requiring an outpatient consultation or hospital admission within 30 days of the procedure. According to the Clavien-Dindo classification there were 25 patients (5.9%) with grade I complications, 24 (5.7%) with grade II and one patient (0.2%) with a grade IIIb complication (TUR-P within 30 days as a patients desire). Eleven patients (2.6%) developed an urosepsis (fever >38.5 C), 38 (9%) had an urinary retention requiring urethral catheterization and two (0.5%) had an acute bacterial prostatitis. Of the eleven patients with urosepsis, seven carried Escherichia coli, the other four cases were ESBL, Enterococcus faecalis, Serratia marcenscens and Enterobacter cloacae complex with Staphyloccocus aureus. Those patients had to be hospitalised for 2.5 days on average (range 1-7 days). 37 patients (8.8%) mentioned haematospermia while 93 (22.1%) noticed haematuria within 30 days of the procedure. A binomial logistic regressionshowed that an increasedprostate volumewasassociatedwith an increased likelihood of exhibiting urinary retention (p 1⁄4 0.006). CONCLUSIONS: In this analysis we demonstrated a low morbidity following TMBx. The procedure is very well tolerated and safe for patients. Especially the rate of major infections and urosepsis are low. Haematuria and haematospermia were very common but selflimiting in most of the cases. However, urinary retention is a major complication with 9% of all cases and is associated with increased prostate volume. Therefore we now leave the catheter for two days in patients with larger prostate glands.

PNFBA-10 FOCAL THERAPY OF PROSTATE CANCER: DEFINING APPROPRIATE TREATMENT MARGINS USING MRI:WHOLE MOUNT CO-REGISTRATION

INTRODUCTION AND OBJECTIVES: Precision medicine aims to provide the right treatment for the right patient at the right time with treatment directed on the basis of the targetable tumoral aberrations rather than just a traditional histologic subtype. However to facilitate this approach, clinicians require patient derived samples. Prostate cancer is challenging to culture in vitro. Recent development of novel organoid in vitro culture technology has led to the development of multiple new in vitro prostate cancer cell line models. We aim to apply organoid culture technology to develop novel in vitro prostate cancer cell line models and propagate patient derived samples to allow drug testing and next generation sequencing as part of a precision medicine approach to early recurrent prostate cancer. METHODS: Patient derived metastatic tissue samples were collected as part of a larger clinical trial. These were digested in Type II Collagenase (Gibco) for 2 hours and seeded directly onto Collagen Type I coated plates in novel media. Samples were cultured in vitro for a minimum of 2 weeks prior to validation. PSA ELISA (GenWay Biotech) of conditioned media along with RT-qPCR comparison of various gene products of interest between cultured patient samples and established prostate cancer cell lines was performed. In vitro samples were subsequently utilised for therapeutic screening. RESULTS: A total of 5 patient samples were available for culture with histologically proven metastatic prostate cancer. Tissue from a 67 year old male with biochemical recurrence of prostate cancer following retro-pubic radical prostatectomy was obtained fresh at time of salvage lymph node dissection (PSA was 1.5 ng/ml). Tissue was successfully cultured for a minimum of 4 weeks prior to validation. PSA ELISA of conditioned media was positive. RT-qPCR confirmed expression of Prostate specific genes PSA, AR, FKBP5 and TMPRSS. Drug screen revealed a marked response to Docetaxel, Cabazitaxel and Enzalutamide and minimal effect to Bicalutamide. CONCLUSIONS: We have successfully cultured patient derived samples for precision medicine. Further therapeutic screening and next generation sequencing of derived cultures is ongoing in order to potentially inform therapeutic strategies. Organoid in vitro culture technology could provide a vital stepping stone towards precision medicine in the future, involving the rapid generation of patient specific in vitro models for therapeutic screening to guide individualized treatment.