Sameer Mittal

Reevaluating PSA Testing Rates in the PLCO Trial

The PLCO trial generated data that argue against PSA screening. However, participants in the control group also reported being screened. An analysis of health questionnaires suggests that more than 80% of controls had been tested within the previous 3 years.

Percutaneous embolization of varicocele: technique, indications, relative contraindications, and complications

There are several options for the treatment of varicocele, including surgical repair either by open or microsurgical approach, laparoscopy, or through percutaneous embolization of the internal spermatic vein. The ultimate goal of varicocele treatment relies on the occlusion of the dilated veins that drain the testis. Percutaneous embolization offers a rapid recovery and can be successfully accomplished in approximately 90% of attempts. However, the technique demands interventional radiologic expertise and has potential serious complications, including vascular perforation, coil migration, and thrombosis of pampiniform plexus. This review discusses the common indications, relative contraindications, technical details, and risks associated with percutaneous embolization of varicocele.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer

Purpose: Guidelines from the NCCN® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. Materials and Methods: We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person‐years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. Results: A total of 1,713 clinically significant prostate cancers were detected with a 10‐year cumulative incidence of 5.9% (95% CI 5.6–6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Conclusions: Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity.

Efficacy of Prostate-Specific Antigen Screening: Use of Regression Discontinuity in the PLCO Cancer Screening Trial

Acquisition, analysis, or interpretation of data: Yu, Tian, Drilon, Borsu, Arcila, Ladanyi. Drafting of the manuscript: Yu, Tian, Drilon, Borsu, Arcila, Ladanyi. Critical revision of the manuscript for important intellectual content: Yu, Tian, Drilon, Riely, Arcila, Ladanyi. Interpretation of molecular results: Arcila. Obtained funding: Ladanyi. Administrative, technical, or material support: Yu, Tian, Drilon, Borsu. Study supervision: Drilon, Riely, Arcila, Ladanyi.

Vasectomy and Risk of Prostate Cancer in a Screening Trial

Background: Vasectomy has been implicated as a risk factor for prostate cancer in multiple epidemiologic studies over the past 25 years. Whether this relationship is causal remains unclear. This study examines the association between vasectomy and prostate cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which randomized men to usual care or annual prostate cancer screening. Methods: We performed a retrospective analysis of 13-year screening and outcomes data from the PLCO trial. Multivariable Cox proportional hazards regression stratified by study arm and age at vasectomy was performed. Results: There was an increased risk of prostate cancer in men who had undergone a vasectomy and were randomized to the usual care arm of the study (adjusted HR, 1.11; 95% confidence interval, 1.03–1.20; P = 0.008). There was no association between vasectomy and diagnosis of prostate cancer in men randomized to the prostate cancer screening arm. Only men undergoing vasectomy at an older age in the usual care arm of the study, but not the prostate cancer screening arm, were at increased risk of being diagnosed with prostate cancer. Conclusions: Vasectomy was not associated with prostate cancer risk among men who were screened for prostate cancer as part of a clinical trial, but was associated with prostate cancer detection in men receiving usual care. Impact: The positive association between vasectomy and prostate cancer is likely related to increased detection of prostate cancer based on patterns of care rather than a biological effect of vasectomy on prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(11); 1653–9. ©2017 AACR.

Lethal Prostate Cancer in the PLCO Cancer Screening Trial

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial randomized men to usual care or annual prostate-specific antigen (PSA) screening for 6 yr and digital rectal examination for 4 yr. This trial found no difference between the intervention and usual care arms of the study in the primary end point of prostate cancer (PCa)-specific mortality. The PLCO trial results have had a major impact on health policy and the rate of PSA screening in the United States. We analyzed the 13-yr screening and outcomes data from the 151 participants who died of PCa in the screening arm of the trial to better understand how randomization to screening failed to prevent PCa death in these men. We found that of these men, 81 (53.6%) either were never screened as part of the trial or had an initial positive screen. Only 17 (11.3%) of those who died reached year 6 of the trial with a PSA <4.0 ng/ml. The men who died in the screening arm were also older at study entry than the average PLCO participant (66 vs 62 yr; p < 0.001). Our analysis should inform the interpretation of the PLCO trial and provide insight into future trial design.

PD68-01 PILOT STUDY RESULTS USING FLUORESCENCE ACTIVATED CELL SORTING OF SPERMATOZOA FROM TESTIS TISSUE: A NOVEL METHOD FOR SPERM ISOLATION AFTER TESE

INTRODUCTION AND OBJECTIVES: Testicular sperm extraction (TESE) is successful in identifying a small number of sperm in 50% of men with non-obstructive azoospermia (NOA). Traditionally, sperm are isolated from testicular tissue using a combination of standard light microscopy, tissue digestion and time analyzing the specimen in hope to isolate rare spermatozoa. Here we discuss our results utilizing fluorescence-activated cell sorting (FACS) of testis tissue to increase the efficiency in the isolation of spermatozoa. METHODS: Testicular tissue was obtained from 10 patients: 2 cadaveric specimens with normal spermatogenesis and 8 specimens from wasted testicular tissue from microTESE. The specimens were prepared by sharp cutting followed by mechanical disaggregation with a Medimachine (BD Biosciences, USA) and passed through a 50and 30micron filter. The specimens were then stained with DNA-stains To-Pro3 or SYTO 17(ThermoFischer, USA) and incubated. Sperm from a normal semen sample were stained similarly and used as controls for gating during flow cytometry . Then, cell sorting was completed using a FACSAria II (BD Biosciences, USA) to isolate spermatozoa. Each sorted specimen underwent standard light microscopy to identify spermatozoa. RESULTS: Using this technique, spermatozoa were successfully isolated and recovered in both cadaveric specimens. Of the 8 patients undergoing microTESE , 3 (38%) had spermatozoa recovered using standard tissue processing and 4 (50%) had spermatozoa recovered using FACS. Notably, in our cohort, both patients with maturation arrest had a negative microTESE with standard tissue processing, but had successful isolation of spermatozoa using FACS. CONCLUSIONS: Our initial experience using fluorescenceactivated cell sorting for rare spermatozoa isolation from testicular tissue proves the technical feasibility of this process. As this research continues to be refined and implemented, the clinical application of this technique has the potential to increase the rate of successful TESE to isolate spermatozoa.

MP02-13 MICRORNA EXPRESSION PROFILING OF PROSTATE TISSUE SUGGESTS MIR-509-3P AS A DIAGNOSTIC MARKER FOR PROSTATIC ADENOCARCINOMA

of EVs in prostate cancer (PCa). We aimed to investigate the prognostic potential of prostate-specific EVs in PCa patients. METHODS: Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n1⁄482) or benign prostatic hyperplasia (BPH, n1⁄428). To analyze the quantity of EVs in prostatic tissue, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA) antibodies, and immunofluorescence staining. After EV isolation from plasma using an aqueous two-phase system, CD63 and PSMA concentration was measured using ELISA kits. Relationship between plasma EV concentration and clinicopathologic outcomes were analyzed. RESULTS: PSMA-positive areas in prostate tissue differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p<0.001; Fig.1). Plasma concentration of PSMApositive EVs was different among patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p<0.001), and ROC curve analysis indicated that plasma PSMApositive EV concentration differentiated PCa from BPH (AUC 0.943, 95% confidence interval 0.866-0.983; Fig.2). Patients with lower levels of plasma prostate-specific EVs had greater prostate volume (50.2 vs. 33.4 cc, p<0.001) and lower pathologic Gleason score (p1⁄40.025). During the median follow-up of 18 months, patients with a lower levels of prostate-specific EVs tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p1⁄40.085). CONCLUSIONS: Plasma prostate-specific EVs have a potential role in differentiating PCa from BPH. In patients with PCa, lower levels of plasma prostate-specific EVs were associated with favorable pathologic features and better biochemical recurrence-free survival.

MP16-02 INFLUENCE OF INTERDEPARTMENTAL COLLABORATION ON UTILIZATION OF NEOADJUVANT CHEMOTHERAPY PRIOR TO CYSTECTOMY; A 14-YEAR EXPERIENCE

INTRODUCTION AND OBJECTIVES: TeamSTEPPS is a collaborative effort by the Department of Defense and Agency for Healthcare Research and Quality to improve performance and patient safety in the healthcare environment. A commonly stated barrier to implementation of TeamSTEPPS is the time requirement of healthcare personnel during a busy operative schedule and the perceived consequential adverse effect on operating room efficiency. The purpose of this project is to evaluate the operating room efficiency during the first year of implementation of TeamSTEPPS compared to the prior year in the Department of Urology at a teaching medical center. METHODS: TeamSTEPPS consisted of an initial one-time personnel training session, preoperative briefings at the beginning of each day for each operating room, and postoperative debriefings after each case. The preoperative briefing was led by the surgeon and attended by all healthcare personnel assigned to the specific operating room to discuss concerns unique to each case scheduled for that day. Postoperative debriefings identified areas for improvement. The operative times, on-time start rates, and turnover times of all cases performed by the Department of Urology during the year with TeamSTEPPS were compared to the prior year before implementation of TeamSTEPPS. RESULTS: A total of 1431 cases with TeamSTEPPS and 1513 cases before TeamSTEPPS were compared. Case complexity and distribution among subspecialties were similar between the years with and before TeamSTEPPS. The mean in-room to turnover-to-surgeon time was 13.75 minutes with TeamSTEPPS compared to 14.45 minutes before TeamSTEPPS (p1⁄40.017). The mean turnover-to-surgeon to surgical-start timewas15.19minuteswith TeamSTEPPSand16.29minutes before TeamSTEPPS (p1⁄40.004). The mean surgical time with TeamSTEPPS was 72.23 minutes compared to 83.45 minutes before TeamSTEPPS (p<0.001). The on-time first-start rate was 69.8% with TeamSTEPPS while the rate before TeamSTEPPS was 48.9% (p<0.001). The mean room turnover time of 40.49 minutes with TeamSTEPPS was not significantly different than the before TeamSTEPPS time of 41.48 minutes (p1⁄40.193). CONCLUSIONS: The time requirement by healthcare personnel to participate in daily TeamSTEPPS briefings does not adversely affect operating room efficiency. TeamSTEPPS improves operating room efficiency by decreasing operating room time and increasing on-time first-start rates.