Michael Fenstermaker

Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion–targeted Prostate Biopsy Outcomes

BACKGROUND Increasing evidence supports the use of magnetic resonance imaging (MRI)-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). OBJECTIVE To compare MRF-TB and SB results and investigate the relationship between biopsy outcomes and prebiopsy MRI. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-mo period. A total of 601 of 803 consecutively eligible men were included. INTERVENTIONS All men were offered prebiopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. OUTCOMES Detection rates for all PCa and high-grade PCa (Gleason score [GS] ≥7) were compared using the McNemar test. RESULTS AND LIMITATIONS MRF-TB detected fewer GS 6 PCas (75 vs 121; p<0.001) and more GS ≥7 PCas (158 vs 117; p<0.001) than SB. Higher mSS was associated with higher detection of GS ≥7 PCa (p<0.001) but was not correlated with detection of GS 6 PCa. Prediction of GS ≥7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS ≥7 PCas in men with no prior biopsy (88 vs 72; p=0.012), in men with a prior negative biopsy (28 vs 16; p=0.010), and in men with a prior cancer diagnosis (42 vs 29; p=0.043). MRF-TB detected fewer GS 6 PCas in men with no prior biopsy (32 vs 60; p<0.001) and men with prior cancer (30 vs 46; p=0.034). Limitations include the retrospective design and the potential for selection bias given a referral population. CONCLUSIONS MRF-TB detects more high-grade PCas than SB while limiting detection of GS 6 PCa in men presenting for prostate biopsy. These findings suggest that prebiopsy multiparametric MRI and MRF-TB should be considered for all men undergoing prostate biopsy. In addition, mSS in conjunction with biopsy indications may ultimately help in identifying men at low risk of high-grade cancer for whom prostate biopsy may not be warranted. PATIENT SUMMARY We examined how magnetic resonance imaging (MRI)-targeted prostate biopsy compares to traditional systematic biopsy in detecting prostate cancer among men with suspicion of prostate cancer. We found that MRI-targeted biopsy detected more high-grade cancers than systematic biopsy, and that MRI performed before biopsy can predict the risk of high-grade cancer.

A regulatory role for microRNA 33* in controlling lipid metabolism gene expression.

ABSTRACT hsa-miR-33a and hsa-miR-33b, intronic microRNAs (miRNAs) located within the sterol regulatory element-binding protein 2 and 1 genes (Srebp-2 and -1), respectively, have recently been shown to regulate lipid homeostasis in concert with their host genes. Although the functional role of miR-33a and -b has been highly investigated, the role of their passenger strands, miR-33a* and -b*, remains unclear. Here, we demonstrate that miR-33a* and -b* accumulate to steady-state levels in human, mouse, and nonhuman primate tissues and share a similar lipid metabolism target gene network as their sister strands. Analogous to miR-33, miR-33* represses key enzymes involved in cholesterol efflux (ABCA1 and NPC1), fatty acid metabolism (CROT and CPT1a), and insulin signaling (IRS2). Moreover, miR-33* also targets key transcriptional regulators of lipid metabolism, including SRC1, SRC3, NFYC, and RIP140. Importantly, inhibition of either miR-33 or miR-33* rescues target gene expression in cells overexpressing pre-miR-33. Consistent with this, overexpression of miR-33* reduces fatty acid oxidation in human hepatic cells. Altogether, these data support a regulatory role for the miRNA* species and suggest that miR-33 regulates lipid metabolism through both arms of the miR-33/miR-33* duplex.

Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection through Improved Risk Stratification.

PURPOSE MRF-TB (magnetic resonance imaging-ultrasound fusion targeted prostate biopsy) may improve the detection of prostate cancer in men presenting for prostate biopsy. We report clinical outcomes of 12-core systematic biopsy and MRF-TB in men who presented for primary biopsy and further describe pathological characteristics of cancers detected by systematic biopsy and not by MRF-TB. MATERIALS AND METHODS Clinical outcomes of 452 consecutive men who underwent prebiopsy multiparametric magnetic resonance imaging followed by MRF-TB and systematic biopsy at our institution between June 2012 and June 2015 were captured in an institutional review board approved database. Clinical characteristics, biopsy results and magnetic resonance imaging suspicion scores were queried from the database. RESULTS Prostate cancer was detected in 207 of 382 men (54.2%) with a mean±SD age of 64±8.5 years and mean±SEM prostate specific antigen 6.8±0.3 ng/ml who met study inclusion criteria. The cancer detection rate of systematic biopsy and MRF-TB was 49.2% and 43.5%, respectively (p=0.006). MRF-TB detected more Gleason score 7 or greater cancers than systematic biopsy (117 of 132 or 88.6% vs 102 of 132 or 77.3%, p=0.037). Of 41 cancers detected by systematic biopsy but not by MRF-TB 34 (82.9%) demonstrated Gleason 6 disease, and 26 (63.4%) and 34 (82.9%) were clinically insignificant by Epstein criteria and a UCSF CAPRA (University of California-San Francisco-Cancer of the Prostate Risk Assessment) score of 2 or less, respectively. CONCLUSIONS In men presenting for primary prostate biopsy MRF-TB detects more high grade cancers than systematic biopsy. Most cancers detected by systematic biopsy and not by MRF-TB are at clinically low risk. Prebiopsy magnetic resonance imaging followed by MRF-TB decreases the detection of low risk cancers while significantly improving the detection and risk stratification of high grade disease.

Risk Stratification by Urinary Prostate Cancer Gene 3 Testing Before Magnetic Resonance Imaging-Ultrasound Fusion-targeted Prostate Biopsy Among Men With No History of Biopsy

OBJECTIVE To determine whether a combination of prostate cancer gene 3 (PCA3) and magnetic resonance imaging (MRI) suspicion score (mSS) could further optimize detection of prostate cancer on MRI fusion-targeted biopsy (MRF-TB) among men with no history of biopsy. MATERIALS AND METHODS We included in this study 187 men presenting to our institution between June 2012 and August 2014 who underwent multiparametric MRI (mpMRI) and PCA3 before MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics curves and multivariable logistic regressions were used to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (area under the curve: 0.67, 95% confidence interval: 0.59-0.76). Using a cutoff of ≥35, PCA3 was associated with cancer risk among men with mSS 2-3 (P = .004), but not among those with mSS 4-5 (P = .340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (area under the curve: 0.83 vs 0.79, P = .0434). CONCLUSION Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high-suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB, adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.

Long-term Satisfaction After Open Radical Prostatectomy

OBJECTIVE To determine the association between baseline factors, post-treatment factors, and long-term satisfaction after radical prostatectomy (RP). METHODS Between January 2000 and March 2009, 1425 men who underwent RP by a single surgeon were enrolled in an institutional review board-approved, prospective, longitudinal outcomes study. Baseline characteristics and post-treatment functional and oncologic outcomes were captured through 2013. Patient survey responses from 875 (61.4%) of these men were used to evaluate satisfaction with treatment outcome and treatment decision. RESULTS Overall, 88.2% and 91.0% men were satisfied to very satisfied with treatment outcome and treatment decision, respectively. Baseline sexual function was associated with satisfaction with both treatment outcome (adjusted odds ratio [aOR] = 1.40; 95% confidence interval [CI], 1.01-1.93) and treatment decision (aOR = 1.47; 95% CI, 1.08-2.01). Among post-treatment factors, higher University of California, Los Angeles Prostate Cancer Sexual Function (aOR = 2.95; 95% CI, 2.06-4.22), University of California, Los Angeles Prostate Cancer Urinary Function (aOR = 2.38; 95% CI, 1.66-3.40), and lower urinary tract symptom scores (aOR = 1.91; 95% CI, 1.19-3.06) were predictors of satisfaction with outcome. Bother due to incontinence and sexual dysfunction, and perception of cure were independent predictors of both satisfaction with treatment outcome and treatment decision. CONCLUSION Nearly 90% of men are satisfied with both their treatment outcome and treatment decision after open RP. Improving long-term satisfaction after RP requires efforts to provide realistic expectations and improve functional outcomes.

Abstract A15: How does doctor-patient communication about prostate cancer screening influence African-American patients' decisional conflict around screening decisions?

Background: Decisional conflict is the state of uncertainty about the course of action to take. The decisional conflict scale measures personal perceptions of uncertainty in choosing options. Because experts in the medical community disagree about whether men should get screened for prostate cancer, the decision to get screened is often less certain than that for other tests. In order to make the best decisions about prostate cancer screening, patients must be well-informed of both the risks and benefits of screening. In this study, we assessed whether talking to a doctor about risks and benefits was associated with decisional conflict. Methods: A total of 86 African-American men recruited in community-based and faith-based settings completed a baseline survey as part of a prostate cancer education program. The survey incorporated a revised version of the Decisional Conflict Scale. Participants responded “yes”, “unsure” or “no”, and these were scored as 1, 2, and 3 respectively. Scores for each of 10 items were averaged to obtain a decisional conflict score. The survey also included demographic information, questions about participants9 experiences with prostate cancer screening, questions about past communication with physicians about screening, knowledge about prostate cancer, and health practices. All responses were self-reported. After the survey, participants took part in an in-depth prostate cancer information session lead by a physician or a community health worker. For this study, analyses were limited to responses from the baseline survey. Results: The demographics of this sample include African American males of mean age 57.8 (sd 12.4), the majority of whom have at least some college education (72.0%). Most participants completed prostate cancer screening in the past year (57.4%). Half of the men completed a PSA test in the past year (49.4%), and 41% completed DRE. The majority of participants had discussed prostate cancer screening with their doctors (75.6%), and had discussed the benefits of screening with their doctors (67.4%). However, less than half (44.2%) had discussed the risks of prostate cancer screening with their doctors, and even fewer had doctors who informed them that experts disagree about whether men should have a PSA test (26.7%). We found that decisional conflict was negatively associated with having a previous PSA test (β=-0.378, p=0.007), having a doctor who talked with the participant about the benefits of testing (β=-0.424, p=0.002), having a doctor who talked with the participant about the risks of participating (β=-0.392, p=0.001), and with having a doctor who informed them that experts disagree on the need for PSA testing (β=-0.601, p Conclusions: Well-informed patients experience lower decisional conflict. While few participants discussed risks or the lack of consensus about whether men should be screened with their doctors, we found that discussing the risks and disagreement about testing, in addition to the benefits of testing, were significantly associated with having lower decisional conflict scores compared to those who had not had such conversations with their doctors. In addition, previous PSA testing was associated with lower decisional conflict. These results suggest that, to facilitate better decisions about this controversial topic among black men, doctors should consider more open discussion about prostate cancer screening, and that they include the risks, benefits, and controversies in their conversations with patients. Citation Format: Michael Fenstermaker, Theodore Hickman, Heather Gold, Danil Makarov, Stacy Loeb, Helen Cole, Elizabeth Cahn, Joseph Ravenell. How does doctor-patient communication about prostate cancer screening influence African-American patients9 decisional conflict around screening decisions? [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A15.

MP77-18 OUTCOMES OF MRI-US FUSION TARGETED PROSTATE BIOPSY IN MEN WITH HISTORY OF PROSTATIC INTRAEPITHELIAL NEOPLASIA AND/OR ATYPICAL SMALL ACINAR PROLIFERATION: EVIDENCE FOR AN ALTERATION OF CURRENT PRACTICE.

INTRODUCTION AND OBJECTIVES: While PCA3 has been shown to be predictive of prostate cancer (CaP) detection in the setting of systematic biopsy (SB), performance in the setting of targeted MRI-ultrasound fusion biopsy (MRF-TB) is not well described. METHODS: Biopsy results in all men undergoing both SB and MRF-TB, using the Artemis/Pro fuse system, between June 2012 and June 2014 were reviewed. PCA3 scores, highest MRI suspicion score (mSS), and cancer detection rates were extracted from 143 patients without a previous cancer diagnosis. Receiver operating characteristics (ROC) were analyzed to determine the performance of PCA3 in predicting cancer on MRF-TB at varying thresholds. In bivariable analyses, the association between elevated PCA3 and MRF-TB findings were analyzed. The predictive capability of PCA3þmSS was compared to that of mSS alone by fitting multivariable logistic regression models and comparing ROC and areas under the curve (AUC). RESULTS: Table 1 summarizes the predictive capability for Gleason 3þ3 or higher disease on MRF-TB, stratified by threshold. In bivariable analyses using a threshold of 35, a greater proportion of those with a high PCA3 demonstrated cancer on MRF-TB than those with a low PCA3 (46.8% vs. 18.8%, p < 0.001). Similarly, patients with a high PCA3 and mSS 3 were more likely to have cancer on MRF-TB than those with a low PCA3 and mSS 3 (48.8% vs. 26.7%, p 1⁄4 0.004). In multivariable analyses, a logistic regression model containing both PCA3 and mSS was associated with significantly higher discrimination of cancer on MRF-TB compared to a model of mSS alone (AUC 0.786 vs. 0.741, p 1⁄4 0.038). Potential study cohort outcomes by threshold are detailed in Table 2 CONCLUSIONS: The predictive capability of PCA3 for prostate cancer is retained in the setting of MRF-TB. Addition of PCA3 to mSS would improve the overall diagnostic accuracy of MRF-TB, but further work is needed to determine the impact of PCA3 at individual thresholds.

PD32-01 COMPARISON OF MRI-US FUSION TARGETED BIOPSY AND SYSTEMATIC PROSTATE BIOPSY: SINGLE INSTITUTION EXPERIENCE IN 604 PATIENTS.

INTRODUCTION AND OBJECTIVES: The aim of the study was to compare partial cystectomy (PC) and radical cystectomy (RC) with respect to 90-day mortality as well as long-term, all cause (ACM) and cancer specific mortality (CSM). METHODS: Using the SEER-Medicare database 3913 patients with T2-T3 urothelial carcinoma of the urinary bladder (UCUB) who underwent either RC (n1⁄43419) or PC (n1⁄4494) were identified. After propensity score matching to reduce potential treatment selection bias, 90day mortality, ACM-free and CSM-free rates between patients treated with PC and RC were estimated. Multivariable regression models (MVA) addressed 90-day mortality as well as 5-years ACM and CSM. RESULTS: After matching, 33% (n1⁄4494) and 67% (n1⁄4988) patients treated respectively with PC or RC remained. Median follow-up was 26months. The 90-daymortality rate was 3.2% (n1⁄416) after PC and 8.1% (n1⁄480) after RC (p1⁄40.001). In MVA, PC vs. RC was associated with a lower 90-day mortality (p<0.001). At 5 years the ACM-free survival rate was 38% after PC and 40% after RC (p1⁄40.3) and failed to differ in MVA (p1⁄40.9). At 5 years the CSM-free survival rate was 59%after PC and 62% after RC (p1⁄40.2) and also failed to differ in MVA (p1⁄40.57). The same results were observed after restriction to patients with pT2N0 UCUB. CONCLUSIONS: Relative to RC, PC is associated with lower short-term mortality and the same long-term ACM and CSM rates. These observations should encourage greater consideration to PC in those selected cases when this type of surgery may be applied.

PD4-11 THE RELATIONSHIP OF INCREASING MRI SUSPICION SCORE AND THE IDENTIFICATION OF HIGH GRADE PROSTATE CANCER ON MRI FUSION TARGETED BIOPSY.

INTRODUCTION AND OBJECTIVES: Multi-parametric MRI (mpMRI) suspicion scores (mSS) can help predict the likelihood of prostate cancer (PCa) on prostate biopsy (PB). In combination with MRI fusion targeted biopsy (MRF-TB), mSS has the potential to reduce over-detection of indolent PCa through avoidance of low risk biopsies. In this study we report the relationship of mSS and PB outcomes among men undergoing systematic biopsy (SB) and MRF-TB following mpMRI. METHODS: Between 6/2012 and 8/2014, all 824 men presenting to our institution for prostate biopsy underwent pre-biopsy mpMRI followed by PB. Outcomes were recorded in an IRB-approved database. For this analysis, biopsy results and mSS were queried from those who underwent both SB and MRF-TB using the Artemis/Profuse (Eigen, Grass Valley) co-registration system. RESULTS: 604 men (mean age 65 8 years; BMI 27.1 4.3; PSA 6.7 7.2 ng/ml) met inclusion criteria. Overall, increasing mSS correlates with a step-wise increase in detection of GS 7 PCa with both SB [r1⁄4.95] and MRF-TB [r1⁄40.95]. This finding is not seen in GS6 PCa detection with either SB [r1⁄4-0.10] or MRF-TB [r1⁄4-0.23] (See figure 1). For mSS 4/5, MRF-TB detected fewer GS6 PCa [p1⁄40.013] and detected more GS 7 PCa [p1⁄40.001] as compared to SB. When evaluating the cohort by PB indication, for mSS 4/5, FB detected less GS6 PCa than SB only in biopsy naive men [p1⁄40.021], but was similar to SB in men with prior negative PB [p1⁄40.628] or on active surveillance [p1⁄40.114]. However, FB detected more GS 7 PCa compared to SB in all three cohorts with mSS 4/5 [p<0.05 in all 3 cohorts] (See table 1). CONCLUSIONS: Increasing mSS correlates with a higher likelihood of detection of high grade PCa in all men. While this correlation exists with both SB and MRF-TB, in men with mSS 4/5, MRFTB is better at detecting GS 7 PCa while avoiding over-detection of GS6 PCa. In addition, combining mSS and the difference in CDR by biopsy indication can ultimately help identify select men in whom prostate biopsy is unlikely to detect GS& 7 PCa, and PB may be avoided.