Adam Reese

A Recessive Gene for Primary Vesicoureteral Reflux Maps to Chromosome 12p11-q13

Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR. We performed a genome-wide linkage scan in 12 large families segregating pVUR, comprising 72 affected individuals. To avoid potential misspecification of the trait locus, we performed a parametric linkage analysis using both dominant and recessive models. Analysis under the dominant model yielded no signals across the entire genome. In contrast, we identified a unique linkage peak under the recessive model on chromosome 12p11-q13 (D12S1048), which we confirmed by fine mapping. This interval achieved a peak heterogeneity LOD score of 3.6 with 60% of families linked. This heterogeneity LOD score improved to 4.5 with exclusion of two high-density pedigrees that failed to link across the entire genome. The linkage signal on chromosome 12p11-q13 originated from pedigrees of varying ethnicity, suggesting that recessive inheritance of a high frequency risk allele occurs in pVUR kindreds from many different populations. In conclusion, this study identifies a major new locus for pVUR and suggests that in addition to genetic heterogeneity, recessive contributions should be considered in all pVUR genome scans.

PD10-05 UNDERESTIMATION OF PROSTATE CANCER RISK AT DIAGNOSIS AMONG AFRICAN AMERICAN MEN

INTRODUCTION AND OBJECTIVES: African American (AA) men suffer from a disproportionately high burden of clinically significant prostate cancer, with an increased risk of aggressive or advanced stage disease. Even among men thought to have low risk disease at diagnosis, data suggests that AA men are at an increased risk of adverse pathology after radical prostatectomy (RP) compared to men of other races. These data suggest an underestimation of disease risk at diagnosis among AA men. In the current study, we compared preand post-treatment estimates of prostate cancer risk, to determine whether inaccurate assessment of disease risk at diagnosis differs by race. METHODS: We identified Caucasian and AA men who underwent radical prostatectomy (RP) at our institution between 2012 to 2016. CAPRA and CAPRA-S scores were determined as estimates of preand post-operative disease risk, and differences between each patient’s CAPRA and CAPRA-S scores were calculated. Underestimation of disease risk at diagnosis was defined as a CAPRA score less than CAPRA-S score. Rates of risk under and over-estimation were compared among racial groups, and multivariable logistic regression was used to determine factors associated with risk underestimation. RESULTS: 391 men met inclusion criteria, including 284 Caucasian (72.6%) and 107 AA (27.4%) men. As shown in table 1, the distribution of CAPRA and CAPRA-S scores did not differ significantly by race (CAPRA p1⁄40.81, CAPRA-S p1⁄40.69). Differences between each individual patient’s CAPRA and CAPRA-S score are shown in table 2. Risk underestimation occurred in 37% of AA men, compared to 26% of Caucasian men (p 1⁄4 0.09). Multivariable logistic regression showed that AA race (p 1⁄4 0.05) and higher serum PSA at diagnosis (p 1⁄4 0.01) were associated with risk underestimation, whereas age at biopsy, Gleason score, and clinical stage were not. CONCLUSIONS: Underestimation of prostate cancer risk at diagnosis appears to be more common in AA compared to Caucasian men. These findings suggest a need for improved risk assessment at diagnosis, and argue for more aggressive treatment of prostate cancer in AA men.

MP43-16 VARIATION IN ACTIVE SURVEILLANCE UTILIZATION FOR THE MANAGEMENT OF PROSTATE CANCER IN A REGIONAL COLLABORATIVE

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is gaining increasing acceptance as an effective management strategy for men with low risk prostate cancer. We analyzed a regional prostate cancer collaborative in order to characterize variation in the utilization of AS among practitioners and identify factors influencing AS rates. METHODS: The Pennsylvania Urologic Regional Collaborative (PURC), established in 2014, is a voluntary collaborative of urology practices in Southeastern Pennsylvania focused on the evaluation and improvement of prostate cancer care. We prospectively identified men with newly diagnosed prostate cancer across 6 academic and private practice sites from PURC, and determined the percentage of men initially managed with AS. Variations in AS rates by individual practitioner were determined for men with NCCN very low or low risk disease. Demographic and clinicopathologic parameters were assessed to determine how these factors influenced AS rates. RESULTS: Between May 2015 and October 2016, 282 of 1154 (19.6%) men with newly diagnosed prostate cancer underwent AS as initial management strategy, including 82/104 (78.9%) men with NCCN very low and 133/322 (41.3%) with NCCN low risk disease. AS rates stratified by practitioner for men with very low or low risk disease ranged from 11.1% to 100% (Figure 1). Associations of demographic and clinicopathologic parameters with AS rates are shown in the Table. High PSA, Gleason score, clinical stage, and NCCN risk category were all strongly associated with decreased utilization of AS (all p-values < 0.01). CONCLUSIONS: Recent data report AS rates as high as 91% and 74% for NCCN very low and low risk prostate cancer, respectively. In the PURC collaborative, we observed lower rates of AS utilization for men with low risk prostate cancer, and significant variation in AS utilization among practitioners. These findings demonstrate the potential importance of quality collaboratives such as PURC in helping to identify variations in care and targets for quality improvement within local markets. Source of Funding: Data was provided with permission from the Pennsylvania Urologic Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern Pennsylvania hospitals and health systems.

1847 PATHOLOGICAL CHARACTERISTICS OF CYSTIC RENAL LESIONS

INTRODUCTION AND OBJECTIVES: The Bosniak classification system for cystic renal lesions has enabled practitioners to predict the likelihood of malignancy based on pre-operative imaging. However, the histology and grade of these cystic renal lesions is poorly characterized. We aimed to describe the pathological findings of cystic renal lesions removed due to concern for malignancy. METHODS: We performed a retrospective analysis of our institutional database of renal procedures. We included all patients who underwent radical or partial nephrectomy between 2004 and 2010 for cystic renal lesions concerning for malignancy. The Bosniak score of these lesions was determined based on pre-operative imaging; pathological findings following nephrectomy were analyzed. RESULTS: We identified 126 patients who met the inclusion criteria and underwent surgery for 23 Bosniak II lesions (18%), 33 Bosniak III lesions (26%), 45 Bosniak IV lesions (36%), and 25 cystic lesions in which data was insufficient to assign a Bosniak score (20%). On pathological analysis, 36 lesions (29%) were found to be benign and 90 (71%) were malignant. When grouped by Bosniak score, malignancy was identified 30%, 64%, and 89% of Bosniak II, III, and IV lesions, respectively. Of the 90 malignant lesions, 48 (53%) were clear cell renal cell carcinomas (RCCs), 23 (26%) were papillary RCCs, 5 (6%) were mixed clear cell and papillary RCCs, 4 (4%) were chromophobe RCCs, and 10 (11%) were non-RCC histologies. The pathological characteristics of the RCCs, stratified by histology, are shown in the Table. Tumor size, pathological stage, and Fuhrman grade did not significantly differ by tumor histology. Surgical margins were negative in all but 1 (1%) of the malignant lesions. There was no association between pathological stage (p 0.40) or tumor size (p 0.20) and Fuhrman grade. CONCLUSIONS: Papillary histology is slightly more common in cystic RCCs than in solid lesions. Furthermore, the majority of cystic RCCs are low stage, low grade tumors, suggesting that these lesions may behave in a more indolent fashion than solid renal tumors and may be more amenable to active surveillance.