Alan Priester

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.

Robotic ultrasound systems in medicine

Robots ultrasound (RUS) can be defined as the combination of ultrasound imaging with a robotic system in medical interventions. With their potential for high precision, dexterity, and repeatability, robots are often uniquely suited for ultrasound integration. Although the field is relatively young, it has already generated a multitude of robotic systems for application in dozens of medical procedures. This paper reviews the robotic ultrasound systems that have been developed over the past two decades and describes their potential impact on modern medicine. The RUS projects reviewed include extracorporeal devices, needle guidance systems, and intraoperative systems.

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.

Focal Therapy Eligibility Determined by Magnetic Resonance Imaging/Ultrasound Fusion Biopsy

Purpose: We assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy. Materials and Methods: Subjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings. Results: Of the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology. Conclusions: Using intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility.

Focal Laser Ablation of Prostate Cancer

Herein, we describe a case of a 63-year-old male who underwent magnetic resonance imaging (MRI)-guided biopsy of a suspicious lesion in the prostate followed by focal laser ablation. Radical prostatectomy was performed 15 months following focal laser ablation for persistent cancer adjacent to the treatment zone. We provide images from the initial MRI, postablation MRI, and the whole-mount radical prostatectomy specimen. The present case demonstrates the confined, localized effect of focal laser ablation, and also illustrates the advantage of expanded treatment margins.

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.

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.