INTRODUCTION AND OBJECTIVE: The biological trajectory of low-grade (Grade Group 1 [GG1]) prostate cancer in men on active surveillance (AS) is unknown. Using magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy and next generation sequencing (NGS), we examined the clonal fate of GG1 disease and assessed the capacity of tissue-based molecular biomarkers to predict grade progression during follow-up. METHODS: This was a nested case-control study of men with GG1 cancer enrolled in AS at the University of California – Los Angeles. All men underwent MRI/US fusion biopsy at two time points from 2012-2017, and specific tumor foci were tracked and re-sampled using this platform. Cases were defined by upgrading detected at second biopsy; controls did not undergo upgrading on second biopsy. We performed ERG immunohistochemistry (IHC) and targeted DNA/RNA NGS on formalin-fixed paraffin-embedded (FFPE) initial and repeat biopsy specimens to assess tumor clonality and evaluate the association of gene expression markers with grade progression. RESULTS: Sixty-seven men of median age 64 years (IQR 59-69) and PSA 4.9 ng/ml (IQR 3.3-6.4) underwent repeat sampling of a single tracked tumor over a median interval of 11 months (IQR 6-13). ERG IHC status was concordant between initial and repeat biopsy in 64 (96%) of 67 subjects (n=134 samples), suggesting sampling of the same clone over time. No recurrent somatic mutations or copy number alterations were associated with grade progression. Derived Cell Cycle Progression score (median 39.9 vs. 48.0, p=0.16), Genomic Prostate Score (median -1.06 vs. -1.20, p=0.9), and Genomic Classifier scores (median -4.07 vs. -4.09, p=0.7) from initial biopsy were not significantly different between men who did versus did not undergo grade progression. Similarly, expression of FOLH1, PCAT4, SChLAP1, and SPINK1 on initial biopsy did not significantly differ based on grade progression status (all p>0.05). CONCLUSIONS: Resampling of the same clonal focus of prostate cancer over time suggests that GG1 disease may undergo grade progression in some cases. Molecular alterations including somatic mutations, copy number alterations, derived genomic classifiers, and single gene expression markers measured on initial biopsy tissue, however, did not predict grade progression. More work is needed to uncover the molecular drivers of grade progression in men with low-grade prostate cancer. Source of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program and Society of Urologic Oncology (S.S.S.). S.S.S., S.A.T., T.M.M. are supported by the Prostate Cancer Foundation. S.A.T. and T.M.M. are supported by the A. Alfred Taubman Medical Research Institute. This project was supported in part by award number R01CA158627 (L.S.M.), 5 P50 CA186786-05 (G.S.P) and P30CA046592 (P.B.) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Additional support was provided by the Beckman Coulter Foundation, the Jean Perkins Foundation, and the Steven C. Gordon Family Foundation. Supported in part by the Department of Defense PC130652 (S.A.T.), W81XWH-14-1-0287 (T.M.M.), and W81XWH1810219 (S.S.S.).

23% of biopsies performed of the treatment site at 6 mos.post therapy.We observed a 45% decrease in mean PSA at 12 months post therapy and no statistically significant change in IPSS and SHIM scores.CONCLUSIONS: Our data indicate that outpatient, transrectally delivered MRI-guided laser focal therapy for prostate cancer is both safe and feasible.In the current climate of cost-reduction and emphasis on minimally-invasive treatment of cancer, focal treatment of prostate cancer may be an attractive option.The precision and controllability achieved under MRI-guidance may have favorable results for cost effectiveness and quality of life without eliminating the possibility of whole-gland treatment in the future.We will continue to follow these men for twenty years as part of an IRB-approved clinical trial (NCT# 02243033) [3].

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I1 Apr 2017PD28-07 TRACKING OF PRIOR POSITIVE SITES BY MRI/US FUSION IMPROVES DETECTION OF GLEASON SCORE UPGRADING Edward Chang, Tonye Jones, Daniel Margolis, Jiaoti Huang, Shyam Natarajan, Devi Sharma, Merdie Delfin, Frederick Dorey, and Leonard Marks Edward ChangEdward Chang More articles by this author , Tonye JonesTonye Jones More articles by this author , Daniel MargolisDaniel Margolis More articles by this author , Jiaoti HuangJiaoti Huang More articles by this author , Shyam NatarajanShyam Natarajan More articles by this author , Devi SharmaDevi Sharma More articles by this author , Merdie DelfinMerdie Delfin More articles by this author , Frederick DoreyFrederick Dorey More articles by this author , and Leonard MarksLeonard Marks More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1241AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gleason Score (GS) upgrading is seen during subsequent biopsy in up to one-third of men in active surveillance (A.S.) programs. Most A.S. biopsies have been performed in a blind fashion. Using MRI/US fusion biopsy, follow-up targeting of MRI lesions can now be performed. We sought to compare such MRI-targeted follow-up biopsies with biopsy of tumor spots outside of MRI-visible lesions. The latter biopsy method, called tracking biopsy, is another feature of MRI/US fusion but has been rarely reported. METHODS Subjects were 138 consecutive men (mean age 63.4 years) enrolled in A.S. (2009-2016), who had 2 subsequent MRI/US fusion (Artemis) biopsies: confirmatory (6-12 months after initial diagnosis) and surveillance (12 months after that). At confirmatory biopsy, MRI targets and a 12-core template were sampled. At surveillance biopsy, MRI lesions were sampled again and tumor spots detected previously by systematic biopsy were also re-sampled, using the 3D tracking function of the Artemis device (accurate within 3 mm) (Figure). At surveillance biopsy, approximately 5 cores were taken by targeting and 5 by tracking. All men had GS6 lesions at confirmatory biopsy. Upgrading to GS≥3+4 at surveillance biopsy was the endpoint. RESULTS At surveillance biopsy, mean PSA was 4.5 ng/ml (IQR 2.6-5.9) and prostate volume was 46.3 cc (IQR 34.5-59.0). Overall rate of upgrading was 19% (26/138). When MRI-visible lesions were resampled without any tracking biopsies being taken (N=59), upgrading was found in 8 (13%). When prior tumor was sampled by tracking an MRI-invisible lesion (N=23), upgrading was found in 6 (24%). When both targeted and tracking biopsies were performed (N=56), upgrading was found in 12 (21%). Of 56 men having both biopsy methods, upgrading in 12 was detected by targeting in 8 and by tracking in 8; however, 4 of the upgrades (50%) were not detected by each method. Upgrading beyond GS7 was only seen in one patient. CONCLUSIONS At surveillance biopsy for men on A.S., tracking biopsy detects GS upgrading as often as biopsies targeting MRI lesions. However, 50% of upgrading detected by one method were missed by the other. Combining methods increased detection of GS upgrading. Tracking of prior positive sites, even when outside of MRI-visible lesions, is a valuable addition to A.S. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e520 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Edward Chang More articles by this author Tonye Jones More articles by this author Daniel Margolis More articles by this author Jiaoti Huang More articles by this author Shyam Natarajan More articles by this author Devi Sharma More articles by this author Merdie Delfin More articles by this author Frederick Dorey More articles by this author Leonard Marks More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyPlenary: Next Frontier1 Apr 2017PNFBA-10 FOCAL THERAPY OF PROSTATE CANCER: DEFINING APPROPRIATE TREATMENT MARGINS USING MRI:WHOLE MOUNT CO-REGISTRATION Tonye Jones, Alan Priester, Shyam Natarajan, Pooria Khoshnoodi, Warren Grundfest, and Leonard Marks Tonye JonesTonye Jones More articles by this author , Alan PriesterAlan Priester More articles by this author , Shyam NatarajanShyam Natarajan More articles by this author , Pooria KhoshnoodiPooria Khoshnoodi More articles by this author , Warren GrundfestWarren Grundfest More articles by this author , and Leonard MarksLeonard Marks More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Focal therapy of prostate cancer (partial gland ablation, PGA) is of keen interest. To determine treatment margins required for complete tumor ablation, we studied men who were eligible for PGA, but underwent radical prostatectomy. The present work differs from prior studies in that accurate co-registration between pre-op multiparametric MRI (mpMRI) slices and whole-mount findings was enabled through use of patient-specific prostate molds to obtain uniform, standardized processing of specimens. METHODS 35 men with localized, organ-confined prostate cancer (CaP) who underwent 3 Tesla mpMRI prior to radical prostatectomy from 2013 to 2015 were subjects. Mean patient age was 63 yrs; median PSA 6.7 ng/ml; and mean prostate volume 37.6 cc. Criteria for focal therapy eligibility were Gleason score ≤4+3 within MRI-visible index tumor, pathologic stage ≤T3a, and no contralateral clinically significant disease. Using T2-weighted images from pre-operative mpMRI, the prostate capsule and suspicious regions of interest (ROIs) were contoured. 3D patient-specific molds, printed in advance of prostatectomy from MRI specifications, were then used to align prostatectomy specimens with mpMRI (Priester et al., J. Urol, 2016). Digitized whole mount sections, sliced at 4.5 mm intervals, provided 3D reconstruction of prostate tumors. Tumors were matched with ROIs and the relative 3D surfaces were compared to determine appropriate treatment margins. RESULTS 39 of 62 (63%) prostate tumors found on whole-mount sections were detected by MRI. 90% of tumors were in PZ, 10% in TZ. Of the 23 tumors not MRI visible, 22 were low volume, Gleason score 3+3. Mean index tumor volume on MRI was 0.59 cc and 1.59 cc on prostatectomy specimen (p<0.001). Median treatment margin required was 10.7mm (FIGURE). Average treatment volume required for complete tumor ablation was 11.4 cc, which comprised 30% of average prostate volume. All subjects would have been successfully treated with hemi-gland ablation. CONCLUSIONS MRI consistently and dramatically underestimates the extent of prostate tumors. In this population, uniformly employing 1cm treatment margins during focal therapy would have resulted in incomplete tumor ablation in 50% of patients. A patient specific treatment plan incorporating tumor size, geometry, and adjacent tissue sampling is a future research priority. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e912-e913 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tonye Jones More articles by this author Alan Priester More articles by this author Shyam Natarajan More articles by this author Pooria Khoshnoodi More articles by this author Warren Grundfest More articles by this author Leonard Marks More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...