Nicole Curci

The Current Role of Biopsy in the Diagnosis of Renal Tumors

The role of percutaneous renal mass biopsy has continued to grow in the last decade. The incidence of small (≤4cm) renal masses has increased dramatically over the past 15 years, attributed to increased use of cross-sectional imaging and subsequent discovery of small renal masses that would otherwise go undetected. Despite increased early detection, there has been no change in the mortality rate from renal cell carcinoma over the past 15 years. Many small renal masses are not life-limiting, and imaging lacks specificity in distinguishing malignant from nonmalignant small renal masses. Thus, percutaneous biopsy has emerged as an integral part of the diagnosis of renal masses in order to better guide their management.

Integration and Diagnostic Accuracy of 3T Nonendorectal coil Prostate Magnetic Resonance Imaging in the Context of Active Surveillance

OBJECTIVE To evaluate the integration of 3T nonendorectal coil multiparametric prostate magnetic resonance imaging (mpMRI) at 2 high-volume practices that routinely use mpMRI in the setting of active surveillance. MATERIALS AND METHODS This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, and dual-institution retrospective cohort study. Subjects undergoing 3T mpMRI without endorectal coil at either study institution over a 13-month period (August 1, 2015-August 31, 2016) were selected based on predefined criteria: clinical T1/T2 Gleason 6 prostate cancer, prostate-specific antigen <15 ng/mL, ≥40 years old, mpMRI within 2 years of prostate biopsy, and Prostate Imaging Reporting and Data System (PI-RADS) v2 score assigned. Subjects surveilled for Gleason ≥3 + 4 prostate cancer were excluded. The primary outcome was detection of Gleason ≥3 + 4 prostate cancer on magnetic resonance-ultrasound fusion biopsy, standard biopsy, or prostatectomy within 6 months following mpMRI. Positive predictive values (PPVs) were calculated. RESULTS A total of 286 subjects (N = 193 from institution 1, N = 93 from institution 2) met the criteria. Most (87% [90 of 104]) with maximum PI-RADS v2 scores of 1-2 did not receive immediate biopsy or treatment and remained on active surveillance. Incidence and PPVs for PI-RADS v2 scores of ≥3 were the following: PI-RADS 3 (n = 57 [20%], PPV 21% [6 of 29]), PI-RADS 4 (n = 96 [34%], PPV 51% [39 of 77]), and PI-RADS 5 (n = 29 [13%], PPV 71% [20 of 28]). No Gleason ≥4 + 3 prostate cancer was identified for PI-RADS v2 scores of 1-3 (0 of 43 with histology). Following mpMRI and subsequent biopsy, 21% (61 of 286) of subjects were removed from active surveillance and underwent definitive therapy. CONCLUSION The 3T nonendorectal coil mpMRI has been integrated into the care of patients on active surveillance and effectively stratifies risk of Gleason ≥3 + 4 prostate cancer in this population.

Impact of Clinical History on Maximum PI-RADS Version 2 Score: A Six-Reader 120-Case Sham History Retrospective Evaluation

Purpose To assess the impact of clinical history on the maximum Prostate Imaging Recording and Data System (PI-RADS) version 2 (v2) score assigned to multiparametric magnetic resonance (MR) imaging of the prostate. Materials and Methods This retrospective cohort study included 120 consecutively selected multiparametric prostate MR imaging studies performed between November 1, 2016, and December 31, 2016. Sham clinical data in four domains (digital rectal examination, prostate-specific antigen level, plan for biopsy, prior prostate cancer history) were randomly assigned to each case by using a balanced orthogonal design. Six fellowship-trained abdominal radiologists independently reviewed the sham data, actual patient age, and each examination while they were blinded to interreader scoring, true clinical data, and histologic findings. Readers were told the constant sham histories were true, believed the study to be primarily investigating interrater agreement, and were asked to assign a maximum PI-RADS v2 score to each case. Linear regression was performed to assess the association between clinical variables and maximum PI-RADS v2 score designation. Intraclass correlation coefficients (ICCs) were obtained to compare interreader scoring. Results Clinical information had no significant effect on maximum PI-RADS v2 scoring for any of the six readers (P = .09-.99, 42 reader-variable pairs). Distributions of maximum PI-RADS v2 scores in the research context were similar to the distribution of the scores assigned clinically and had fair-to-excellent pairwise interrater agreement (ICC range: 0.53-0.76). Overall interrater agreement was good (ICC: 0.64; 95% confidence interval: 0.57, 0.71). Conclusion Clinical history does not appear to be a substantial bias in maximum PI-RADS v2 score assignment. This is potentially important for clinical nomograms that plan to incorporate PI-RADS v2 score and clinical data into their algorithms (ie, PI-RADS v2 scoring is not confounded by clinical data).

Abstract B036: Comprehensive transcriptomic profiling challenges the robustness of prostate cancer prognostic signatures to multifocality

Purpose: Imaging and tissue-based biomarkers are increasingly utilized in men diagnosed with low-grade prostate cancer (PCa) to guide definitive management vs. active surveillance. PCa is uniquely multifocal, with multiple clonally distinct tumor foci present in the majority of men. A single tumor focus may also be composed of both low- and high-grade components. Hence, an ideal prognostic biomarker should be robust to both undersampling of a high-grade component, as well as a not sampled multifocal high-grade tumor focus. Materials and Methods: To assess the robustness of prognostic biomarkers to multifocality, we designed a comprehensive multiplexed targeted RNA sequencing assay (mxRNAseq) capable of assessing multiple classes of transcriptional alterations and deriving available prognostic signature scores (e.g., Prolaris CCP and OncotypeDX GPS). We applied this assay to a retrospective, multi-institution cohort of over 150 formalin-fixed, paraffin-embedded tissue samples representing the range of prostate cancer progression. Single candidate biomarkers and derived prognostic signatures were compared between low-grade foci in cases with and without high-grade foci, all-low-grade foci vs. all-high-grade foci, and cases with extremes of grade differences in multifocal tumors. Frequency of clinically relevant extreme multifocality was determined by identifying patients in a single-institution consecutive prostatectomy database over 9 years who had exclusively low-grade cancer on biopsy but very-high-grade disease on prostatectomy. Results: Our mxRNAseq assay robustly detected known coding gene/lncRNA expression, gene fusions and splice variants, and expressed mutations and germline variants. Supervised hierarchical clustering of target gene expression confirmed expected transcriptional module deregulation and derived prognostic signatures across prostate cancer progression. Prognostic biomarkers (including derived signatures) showed no significant differences in expression between low-grade foci from prostates with and without high-grade multifocal tumors and were uniformly higher in high-grade foci vs. low-grade foci from the same case. In four cases of extreme multifocality (Gleason score 6 vs. >=8 foci), prognostic signatures were significantly lower in low-grade foci vs. high-grade foci. In 1,418 men with biopsy Gleason score 3+3=6 or 3+4=7, 21 (1.5%) had Gleason score ≥ 4+4=8, where the biopsy almost certainly did not sample the most clinically relevant focus. Conclusions: Using a novel comprehensive mxRNAseq assay, our results challenge the robustness of prognostic biomarkers between multifocal low- and high-grade prostate cancer foci. Tissue-based prostate cancer prognostic biomarkers should be specifically validated using an extreme multifocality design to support utility in predicting the presence of an unsampled, aggressive multifocal tumor focus. Citation Format: Simpa Salami, Daniel H. Hovelson, Jeremy B. Kaplan, Romain Mathieu, Aaron M. Udager, Nicole Curci, Matthew Lee, Lorena Lazo de la Vega, Martin Susani, Nathalie Rioux-Leclercq, Daniel E. Spratt, Todd M. Morgan, Matthew S. Davenport, Mark A. Rubin, Shariat F. Shahrokh, Scott A. Tomlins, Ganesh S. Palapattu. Comprehensive transcriptomic profiling challenges the robustness of prostate cancer prognostic signatures to multifocality [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B036.

Practical Presentation Pearls: Evidence-based Recommendations From the Psychology and Physiology Literature

Oral presentations remain a common teaching method in academic radiology. The goal of these presentations is to transfer knowledge from the presenters brain to brains in the audience in a way that sticks. A number of studies from the recent psychological and physiological literature offer some rather practical and evidence-based advice on ways to optimize our oral presentations. The purpose of this paper is to summarize this work, and to give examples of how it can be harnessed to increase the efficacy of radiology presentations, whether they are for resident education, a continuing medical education course, or for a scientific presentation at a national radiology meeting.

PD33-05 TARGETED NEXT GENERATION SEQUENCING TO CHARACTERIZE MAGNETIC RESONANCE IMAGING VISIBLE AND INVISIBLE PROSTATE CANCER: BIOLOGICAL INSIGHTS AND THERAPEUTIC IMPLICATIONS

METHODS: Formalin-fixed paraffin embedded (FFPE) primary prostate cancer samples were obtained from the Welsh Cancer Bank. Targeted-NGS was performed using the Life Technologies Ion Torrent: Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion Personal Genome Machine sequencer. The hotspot panel covers ~2800 COSMIC mutations of 50 oncogenes and tumour suppressor genes. Standard IHC techniques were also used concentrating on markers of the Wnt, PI3Kinase (PI3K) and MAP-Kinase (MAPK) oncogenic signalling pathways. RESULTS: 61 primary prostate cancer samples were sequenced, 58 from radical retropubic prostatectomy (RRP) specimens and 3 from transurethral resection of prostate (TURP) sections, with a range of Gleason Scores (GS). 21/61 (34.4%) samples harboured a mutation in a cell cycle pathway gene such as TP53 or RB1 and 3/61 (4.9%) in a DNA repair gene such as ATM. 10/61 (16.5%) of samples harboured a mutation in a gene associated with the Wnt pathway such as APC or CTNNB1. 14/61 (23.0%) of samples analysed had a mutation in a gene commonly associated with the PI3K pathway such as PTEN or AKT1. 5/61 (8.2%) had a mutation in a gene associated with the MAPK pathway such as KRAS. IHC profiles were analysed on 317 prostate samples: 73 normal and 244 cancers. There was greater expression of markers associated with Wnt, PI3K and MAPK signalling pathways in prostate cancer samples when compared to normal samples. There was greater expression in high-risk GSs with some markers associated with biochemical recurrence following RRP. Furthermore, we were able to separate lowand high-risk GS samples based on molecular profiles using markers of the Wnt, PI3K and MAPK and principle components analysis. CONCLUSIONS: Targeted NGS and IHC can identify recurrent mutations and signalling pathway aberrations within primary prostate cancer samples, which have potential to be targeted and used in routine clinical practice. In addition, the molecular signatures of lowand highrisk are different and can be separated using a combination of markers and IHC. This finding could explain the marked difference in the behaviours of these tumours types.

MP08-12 MULTI-INSTITUTIONAL EVALUATION OF MRI AND FUSION BIOPSY IN CONFIRMATORY BIOPSY FOR ACTIVE SURVEILLANCE

INTRODUCTION AND OBJECTIVES: To provide standardization as prostate MRI becomes increasingly utilized, the Prostate Imaging-Reporting and Data System (PIRADS) was developed and has been modified to its latest version (v2). Using biopsy outcome as the standard, we examined the predictive accuracy of a PIRADS 4 or 5 read for clinically significant (Gleason 7+) PCa in a blinded fashion. METHODS: We reviewed our prospectively maintained database of consecutive men who underwent prostate MRI prior to biopsy between September 2014 and December 2015. A proportionally representative sample (based on the original clinical PIRADS v2 interpretation) was selected for re-examination (n1⁄432). The prostate MRIs for these patients were de-identified and were loaded by a blinded third party. Four radiologists of varying levels of experience independently interpreted all prostate MRI, blinded to all clinical information. An 00overread00 was defined as a PIRADS 4 or 5 read with biopsy result of benign prostate or Gleason 6 PCa. An 00under-read00 was defined as a PIRADS 1-3 read with resulting biopsy result of Gleason 7+ PCa. RESULTS: The distribution of accuracy is provided in Table 1. Accurate interpretation ranged from 56% (18/32) to 75% (24/32), and the differences among the radiologists were not significant (p1⁄40.48). The improvement of accuracy with a 00majority read00, as defined by two or more accurate radiologists0 blinded interpretations, over the original clinical read trends toward significance (p1⁄40.16). No clinical variable was predictive of an incorrect 00majority read00, including age, PSA, family history, use of 5-alpha reductase inhibitors, prostate volume, or previous biopsy history. CONCLUSIONS: In a blinded assessment of radiologists at our institution, we find that the predictive accuracy of PIRADS 4 or 5 for clinically significant PCa varies among radiologists independent of experience level. A 00majority read00 performed better than the original clinical interpretation, suggesting that consensus interpretation of prostate MRI may improve predictive accuracy.

MP38-17 CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS WITH VERY LOW-RISK (PI-RADS 1 OR 2) LESIONS BY MULTIPARAMETRIC PROSTATE MAGNETIC RESONANCE IMAGING

INTRODUCTION AND OBJECTIVES: Multiparametric prostate magnetic resonance imaging (mpMRI) utilizing the PI-RADS classification system attempts to identify clinically-significant [Gleason score (GS) 7 or higher] prostate cancer (PCa), with PI-RADS 1 or 2 typically corresponding to very low risk of clinically-significant PCa. In this study, we analyzed the clinicopathologic characteristics of patients undergoing prostate core biopsy (PBx) with PI-RADS 1 or 2 lesions. METHODS: All patients at a single large academic institution who had at most PI-RAD 1 or 2 lesions on mpMRI between 1/1/15 and 6/30/16 and underwent preor post-MRI PBx were retrospectively identified. All cases of clinically-significant PCa were re-reviewed by study pathologists to confirm pathologic findings; clinicopathologic data from all other cases was obtained from pathology reports and electronic medical records. RESULTS: 276 patients with PI-RADS 1 or 2 lesions were identified, of which 98 (35.5%) had either pre(60) or post-MRI (38) inhouse PBx. Six (6.1%) patients showed GS7 PCa (3 preand 3 postMRI), including 2 with GS4+31⁄47 tumors. For the remaining patients, the most recent PBx findings included: GS6 PCa (22 preand 13 post-MRI); atypical glands (3 preand 2 post-MRI); high-grade prostatic intraepithelial neoplasia (5 preand 4 post-MRI); or, benign (27 preand 16 post-MRI). For patients with GS7 PCa, the median number of involved cores was 1 (range 1⁄4 1-3), the median number of total cores was 20 (range 1⁄4 12-30), the median % involvement of a single core was 12.5 (range 1⁄4 5-25), and the median % Gleason pattern 4 was 30 (range 1⁄4 5-90); types of Gleason pattern 4 included: poorly-formed glands only (4), cribriform glands only (1), or poorly-formed and cribriform glands (1). One GS7 tumor occurred in the post-radiation (XRT) setting, and one showed aberrant p63 expression; follow-up for patients with GS7 PCa included primary XRT (1), salvage XRT (1), and active surveillance (AS; 4). Nearly all patients (>90%) with GS6 PCa opted for AS; one patient underwent radical prostatectomy (pT2a GS6 PCa), and one patient was lost to follow-up. CONCLUSIONS: The majority (58.2%) of patients with PIRADS 1 or 2 lesions by mpMRI do not have detectable PCa on core biopsy, however, a small subset (6.1%) harbor GS7 PCa. Although long-term follow-up data are needed, PCa patients with PI-RADS 1 or 2 lesions by mpMRI appear to represent a very low-risk cohort that may be amenable to AS in the majority of cases.

MP38-18 CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS UNDERGOING PROSTATE CORE BIOPSY WITH HIGH-RISK (PI-RADS 5) LESIONS BY MULTIPARAMETRIC PROSTATE MAGNETIC RESONANCE IMAGING.

INTRODUCTION AND OBJECTIVES: Multiparametric prostate magnetic resonance imaging (mpMRI) utilizing the PI-RADS classification system attempts to identify clinically-significant [Gleason score (GS) 7 or higher] prostate cancer (PCa), with PI-RADS 1 or 2 typically corresponding to very low risk of clinically-significant PCa. In this study, we analyzed the clinicopathologic characteristics of patients undergoing prostate core biopsy (PBx) with PI-RADS 1 or 2 lesions. METHODS: All patients at a single large academic institution who had at most PI-RAD 1 or 2 lesions on mpMRI between 1/1/15 and 6/30/16 and underwent preor post-MRI PBx were retrospectively identified. All cases of clinically-significant PCa were re-reviewed by study pathologists to confirm pathologic findings; clinicopathologic data from all other cases was obtained from pathology reports and electronic medical records. RESULTS: 276 patients with PI-RADS 1 or 2 lesions were identified, of which 98 (35.5%) had either pre(60) or post-MRI (38) inhouse PBx. Six (6.1%) patients showed GS7 PCa (3 preand 3 postMRI), including 2 with GS4+31⁄47 tumors. For the remaining patients, the most recent PBx findings included: GS6 PCa (22 preand 13 post-MRI); atypical glands (3 preand 2 post-MRI); high-grade prostatic intraepithelial neoplasia (5 preand 4 post-MRI); or, benign (27 preand 16 post-MRI). For patients with GS7 PCa, the median number of involved cores was 1 (range 1⁄4 1-3), the median number of total cores was 20 (range 1⁄4 12-30), the median % involvement of a single core was 12.5 (range 1⁄4 5-25), and the median % Gleason pattern 4 was 30 (range 1⁄4 5-90); types of Gleason pattern 4 included: poorly-formed glands only (4), cribriform glands only (1), or poorly-formed and cribriform glands (1). One GS7 tumor occurred in the post-radiation (XRT) setting, and one showed aberrant p63 expression; follow-up for patients with GS7 PCa included primary XRT (1), salvage XRT (1), and active surveillance (AS; 4). Nearly all patients (>90%) with GS6 PCa opted for AS; one patient underwent radical prostatectomy (pT2a GS6 PCa), and one patient was lost to follow-up. CONCLUSIONS: The majority (58.2%) of patients with PIRADS 1 or 2 lesions by mpMRI do not have detectable PCa on core biopsy, however, a small subset (6.1%) harbor GS7 PCa. Although long-term follow-up data are needed, PCa patients with PI-RADS 1 or 2 lesions by mpMRI appear to represent a very low-risk cohort that may be amenable to AS in the majority of cases.