Simpa Salami

Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

OBJECTIVES We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. MATERIALS AND METHODS Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. RESULTS Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). CONCLUSIONS A clinical algorithm specifying biopsy for all patients with PSA ≥ 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.

Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies with validation in the Prostate Cancer Prevention Trial.

Limited survival benefit and excess treatment because of prostate‐specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy.

Evaluating Compensatory Hypertrophy: A Growth Curve Specific for Solitary Functioning Kidneys

PURPOSE While compensatory hypertrophy is expected in solitary kidneys, the definition of appropriate hypertrophy remains unclear. The normal renal growth rate in children age 1 to 18 years with 2 kidneys has been defined as 0.28 × age (years) + 6.1. Solitary kidneys appear to grow faster and larger and, thus, require a separate growth curve. MATERIALS AND METHODS The records of all patients 18 years old or younger with solitary functioning kidneys were reviewed from 2001 to 2011. Exclusion criteria were greater than SFU (Society for Fetal Urology) grade 2 hydronephrosis, posterior urethral valves, vesicoureteral reflux or any ipsilateral obstruction. Ordinary least squares regression modeled the renal length as a function of age by using only the initial sonogram per subject. The distribution of mean kidney length by age was plotted and compared to published normal values. RESULTS A total of 91 subjects were included in the study. Patients were evenly split by laterality and gender. Multicystic dysplastic kidney comprised 34% and solitary kidneys 66% of subjects. Of these subjects 55% underwent their first sonogram at younger than 1 year old. There were 61 subjects with multiple sonograms but the initial 91 were included in the study. Age was a better predictor of renal length for subjects age 1 year or older (r(2) = 0.7312) than for those younger than 1 year old (r(2) = 0.6138). For children age 1 to 18 years we used the equation, length = 0.38 × age + 7.2. Solitary kidney values were approximately 2 standard deviations greater than normal values. CONCLUSIONS The equation 0.4 × age (years) + 7 can be used to accurately estimate expected renal length in children (age 1 to 18 years) with solitary kidneys and can be used as a quick reference to evaluate for renal compensatory hypertrophy.

Surveillance strategies in the management of penile cancer

Penile cancer is a rare disease and can be associated with a high risk of recurrence in regional lymph nodes and distant sites. Surveillance strategies geared towards early detection and treatment are recommended given the significant morbidity and mortality associated with recurrences. Although physical examination is the single most important surveillance strategy, imaging is an important adjunct in high-risk disease and certain clinical scenarios.

Intraductal Carcinoma of the Prostate Diagnosed by Multi-Parametric Prostate Magnetic Resonance Imaging (MRI) and MRI/Ultrasound Fusion-Guided Biopsy

Intraductal carcinoma of the prostate (IDC-P) is an aggressive form of prostate cancer (CaP) with clinical and pathological features distinguishing it from high-grade prostatic intraepithelial neoplasia (HG-PIN). IDC-P is characterized by a high volume and high-grade disease, with an aggressive behavior. We present the case of a 63-year-old male with diagnostic MRI imaging indicative of IDC-P. To our knowledge, this is the first reported case of IDC-P identified with multi-parametric MRI.

PD07-12 MOLECULAR PROFILING OF MULTI-FOCAL PROSTATE CANCER AND CONCOMITANT LYMPH NODE METASTASIS: IMPLICATIONS FOR TISSUE-BASED PROGNOSTIC BIOMARKERS

mutation (8%), and 3/62 patients with BRCA2 (5%). Overall,16/24 patients (67%) were surgically treated for their cancer. CONCLUSIONS: Malignancy rates in male BRCA mutation carriers are substantially higher than those reported for the general population in corresponding age groups. Prostate cancer is the most prevalent cancer apparent in up to 8% of patients at a median age of 50 years. Unlike other reports, prostate cancer was prevalent among BRCA1 carriers and not restricted to BRCA2.

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.

V6-06 ROBOTIC-ASSISTED THORACOSCOPIC TRANSDIAPHRAGMATIC ADRENALECTOMY: A NOVEL SURGICAL APPROACH

INTRODUCTION AND OBJECTIVES: Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascular complications such as thrombosis and kinking. Retroperitoneal compartment syndrome (RACS) is an under-recognized vascular cause of EAD with potentially devastating consequences, and may even result in a lost graft. The graft can be salvaged with early recognition and intervention through a mesh hood fascial closure (MHFC) technique. METHODS: Here we describe, in video, a 23-years-old male recipient diagnosed with renal failure secondary to chronic reflux. He has a 6months history of peritoneal dialysis and is currently on hemodialysis. The patient received an anonymous living-donor right kidney from our paired exchange program. His BMI is 22. The graft had a single renal artery and single renal vein. A standard anastomosis was performed and subsequent urine output was brisk. The fascia was closed without tension. However, urine production ceased after the fascia was fully closed. A case of RACS was suspected and intraoperative Doppler ultrasound showed no blood flow in the graft. Immediately re-exploration revealed the graft to be abnormal in color and turgor. RESULTS: These abnormalities resolved after pressure was relieved. The kidney was then placed in the optimal position within the iliac fossa and a large ellipsoid piece of polypropylene mesh was draped loosely and without tension over the graft. The mesh was attached to the posterior fascial edges using interrupted #1 polypropylene sutures. Skin closure then was completed over a closed suction drain placed in the retroperitoneal space lateral to the kidney. Doppler ultrasound after skin closure showed good flow and the postoperative course was unremarkable. CONCLUSIONS: RACS could be associated with small android pelvis and lack of compliance in the retroperitoneal cavity secondary to peritoneal dialysis. Suspected RACS require prompt intervention to prevent irreversible graft dysfunction. We have shown that MHFC is an effective and safe method to treat EAD secondary to RACS.

PD17-02 THE USE OF CYTOLOGY DURING THE WORKUP OF PATIENTS WITH PRIMARY MICROSCOPIC HEMATURIA: GUIDELINE COMPLIANCE PATTERNS AMONG A COHORT OF ACADEMIC UROLOGISTS

INTRODUCTION AND OBJECTIVES: In an effort to improve patient autonomy, several organizations publish online data on surgeon performance. One such organization is Pro-Publica, an independent nonprofit newsroom that publishes an online 0surgeon scorecard.0 This scorecard reports calculated death and complication rates for surgeons performing elective procedures including radical prostatectomy in Medicare patients. We wanted to understand how the general public would interpret this data and how it would impact patients’ selection of surgeon. METHODS: 265 adults at the Minnesota State Fair were asked to interpret a representative image from the Pro-Publica surgeon scorecard. Participants were told that a loved one had already scheduled cancer surgery with a surgeon they trusted. They were then shown a graphic with a dot representing the point estimate complication rate and a bar representing the 95% confidence interval (CI) of their surgeon. They were also shown a graphic with 13 other surgeons’ point estimate complication rates, all of which fell within the CI of the index surgeon’s complication rate. Another surgeon with a 0.5% lower point estimate but statistically equivalent complication rate to the first surgeon was indicated on the graphic. Participants were then asked if they would recommend switching surgeons after seeing this graphic. RESULTS: The surveyed population was educated with 89% having attended or graduated from college (n1⁄4235). Median age of participants was 50 years (range 20-74) with 68% females (n1⁄4179). Participants were from 136 different zip codes predominantly in the upper Midwest. When presented with the graphic representing two surgeons with different point estimate complication rates falling within the same confidence interval, 124 or 46.8% (95% CI 41-53) of respondents would recommend switching surgeons based on this single graphic. CONCLUSIONS: Nearly half of adults surveyed would recommend switching cancer surgeons for genitourinary malignancies based on a graphical representation of surgeons’ complication rates even though there was no statistically significant difference between the two surgeons. This suggests that simplistic displays of complicated statistical data may lead to changes in medical decision-making based on random error of measurement instead of true differences in surgeon quality.

Ability of an epigenetic assay to identify anterior prostate tumors based on a negative 12-core biopsy.

131 Background: There is increasing awareness that anterior-predominant prostate cancers (PCa) are poorly sampled by 12-core transrectal ultrasound-guided (TRUS) prostate biopsies. Approximately one-fifth of all prostate tumors occur in this area, and many are high grade and extend beyond the prostatic capsule. An epigenetic assay, detecting PCa-specific DNA-methylation of GSTP1, RASSF1 and APC has shown to be a significant predictor for the presence of PCa in histopathologically cancer-negative biopsies through a cancer-associated field effect. It is currently unknown whether the field effect from an anterior-predominant cancer may be detected in standard posteriorly-directed sextant biopsy specimens. Methods: Seven patients with at least one prior negative TRUS biopsy were subsequently diagnosed with anterior-only PCa based on a transperineal mapping template prostate biopsy (MTPB). Three patients were diagnosed with low-grade Gleason score (GS) 6 tumors and four patients with GS ≥7 tumors. The outcome ...