Anthony Sisk

Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance

Purpose: Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging‐ultrasound fusion for guidance. Materials and Methods: A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging‐ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real‐time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. Results: Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging‐ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. Conclusions: Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging‐ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy.

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.

Novel association of familial testicular germ cell tumor and autosomal dominant polycystic kidney disease with PKD1 mutation

Adolescent brothers were diagnosed with testicular germ cell tumors within the same month. Both were found to have multiple renal cysts on pretreatment imaging done for staging. The proband, his brother, and their mother, were all found to have a novel splice variant in intron 8 of the PKD1 gene by clinical exome sequencing. This is the second family reported with both familial testicular germ cell tumor (FTGCT) and autosomal dominant polycystic kidney disease (ADPKD), and the first described association of FTGCT with a splice variant in PKD1. We suggest that this novel variant in PKD1 may convey increased risk for FTGCT in addition to causing ADPKD.

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.

Clear cell renal cell carcinoma: identifying PTEN expression on multiphasic MDCT

PurposeTo investigate whether multiphasic MDCT enhancement profiles can help to identify PTEN expression in clear cell renal cell carcinomas (ccRCCs). Lack of PTEN expression is associated with worsened overall survival, a more advanced Fuhrman grade, and a greater likelihood of lymph mode metastasis.MethodsWith IRB approval for this retrospective study, we derived a cohort of 103 histologically proven ccRCCs with preoperative 4-phase renal mass MDCT from 2001–2013. Following manual segmentation, a computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5-cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Maximal lesion attenuation − cortex attenuation)/cortex attenuation] × 100. Absolute and relative attenuation in each phase were compared using t tests. The performance of multiphasic enhancement in identifying PTEN expression was assessed with logistic regression analysis.ResultsPTEN-positive and PTEN-negative ccRCCs both exhibited peak enhancement in the corticomedullary phase. Relative corticomedullary phase attenuation was significantly greater for PTEN-negative ccRCCs in comparison to PTEN-positive ccRCCs (33.7 vs. 9.5, p = 0.03). After controlling for lesion stage and size, relative corticomedullary phase attenuation had an accuracy of 84% (86/103), specificity of 100% (84/84), sensitivity of 11% (2/19), positive predictive value of 100% (2/2), and negative predictive value of 83% (84/101) in identifying PTEN expression.ConclusionRelative corticomedullary phase attenuation may help to identify PTEN expression in ccRCCs, if validated prospectively.

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.

Targeted Prostate Biopsy Using 68Gallium PSMA-PET/CT for Image Guidance

Prostate specific membrane antigen (PSMA) scanning is a sensitive method of prostate cancer detection. In a 71 y.o. man with a PSA of 49 (6%F), 4 negative MRI studies and 6 negative biopsies over an 8 year interval, a 68Ga-PSMA PET/CT scan showed a PSMA-avid spot in the prostate. Using image fusion technology, the lesion was target-biopsied and Gleason 3 + 4 = 7 (cancer core length of 12 mm) was identified. This case may herald a new application for PSMA scanning and prostate cancer imaging.

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.

MP22-07 CORRELATION OF CAD PEAK LESION ENHANCEMENT WITH QUANTITATIVE TUMOR ANGIOGENESIS TO NON-INVASIVELY ASSESS FURHMAN GRADES I-IV IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: To assess if Computer Aided Detection (CAD) of peak lesion attenuation discriminates among Fuhrman Grades I-IV and correlates with an increase in tumor angiogenesis in clear cell RCC (ccRCC) on four-phase MDCT. METHODS: We reviewed a cohort of patients with ccRCC and preoperative multiphasic multidetector CT imaged with a 4-phase renal mass protocol (unenhanced, corticomedullary (C), nephrographic (N), and excretory (E)). A whole lesion 3D contour was obtained in all phases with proprietary software. The CAD algorithm determined a 0.5cm diameter region of peak enhancement 300HU within the 3D lesion contour. For assessment of quantitative angiogenesis, immunohistochemical staining for CD34 to determine microvessel density (MVD) was performed. T-tests were used to compare peak multiphasic enhancement and microvessel density among Fuhrman grades I-IV. P values less than 0.05 were considered to be significant. RESULTS: 107 patients (71(64%) men and 40(35%) women) with 111 unique ccRCC lesions (16 (14%) Fuhrman grade I, 64 (58%) Fuhrman grade II, 23 (21%) Fuhrman Grade III, 8 (7%) Fuhrman grade IV) were analyzed. In the C phase, CAD peak lesion enhancement discriminated grade I from II (150 HU vs. 185 HU, p1⁄40.006), I from III (150 HU vs. 178 HU, p1⁄40.054), I from IV (150 HU vs 229HU, p<0.001). This directly correlated with an increase in quantitative angiogenesis (MVD): I from II (2134 mm2 vs. 4710 mm2, p1⁄40.004), I from III (2134 mm2 vs. 5162 mm, p1⁄40.001), I from IV (2134 mm2 vs 6076 mm2, p1⁄40.057). CONCLUSIONS: CAD peak lesion enhancement discriminates Fuhrman grades 1-IV on multiphasic CT and correlates with an increase in tumor angiogenesis. This may be helpful to triage patients to active surveillance, interventional therapy or, if validated, may be useful to monitor results with anti-angiogenic therapy.