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The 2012 US Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening for all men has been controversial, with data documenting a shift to a higher stage of disease at diagnosis. The association between the Grade D recommendation and prostate cancer-specific mortality (PCSM) among contemporary cohorts, however, is unclear.To evaluate PCSM rates between 1999 and 2019, comparing trends in rates before and after the change in the 2012 USPSTF screening guideline to assess its association with PCSM.The 2012 USPSTF Grade D recommendation against PSA screening for all men.This cross-sectional study used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research maintained by the National Center for Health Statistics to collect data on cause of death for all individuals who died of prostate cancer in the US from 1999 to 2019. Analysis was performed from January to August 2021.Trends in PCSM rates were calculated from 1999 to 2012 and from 2014 to 2019, with a washout year of 2013, using linear regression, with year and binary indicator of pre-2013 and post-2013 status as interaction terms. Trends were further analyzed by age, race and ethnicity, urbanization category, and US Census region. Other measures included diagnosis of localized or metastatic prostate cancer and overall cancer mortality.A total of 618 095 patients died of prostate cancer in the US from 1999 to 2019. Age-adjusted PCSM decreased linearly at a rate of -0.273 per 100 000 population per year from 1999 to 2012 and stalled at a rate of -0.009 per 100 000 per year from 2014 to 2019 (P .001). This finding was significant among men aged 60 years or older, especially among men aged 60 to 69 years, men aged 80 years or older, and among Black men. Men aged 60 to 64 years had a decreasing, age-adjusted PCSM rate of -0.0088 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0014 per 100 000 per year. Men aged 65 to 69 years had a decreasing, age-adjusted PCSM rate of -0.024 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0011 per 100 000 population per year. Men aged 80 years or older had the largest absolute difference between rates before and after 2013 compared with all other age groups, with a difference of 0.06 for men aged 80 to 84 years and 0.07 for men 85 aged years or older. Black men had a decreasing, age-adjusted PCSM rate of -0.700 per 100 000 population per year prior to 2013 followed by a flattened rate of -0.091 per 100 000 population per year. Changes were observed across races and ethnicities, urbanization categories, and US Census regions and were accompanied by increased diagnoses of metastatic disease, which are inconsistent with mortality trends across all malignant neoplasms.This cross-sectional study using comprehensive PCSM data through 2019 demonstrated decreasing PCSM rates that flattened or increased after the 2012 USPSTF Grade D recommendation, suggesting that decreased PSA screening may be a factor associated with this change. This change was seen across ages, races and ethnicities, urbanization categories, and US Census regions. The updated 2018 USPSTF guideline supporting shared decision-making may reverse these trends in the coming years.

OBJECTIVES To develop and validate the Preoperative Risk Evaluation for Partial Nephrectomy (PREP) score to predict the probability of major postoperative complications after partial nephrectomy (PN) based on patient comorbidities. PATIENTS AND METHODS The Premier Healthcare Database was used to identify patients who had undergone elective PN. Through review of International Classification of Diseases ninth revision codes, we identified patient comorbidities and major surgical complications (Clavien-Dindo Grade III-V). Multivariable logistic regression was used to identify predictors of major complications. We used half of the set as the training cohort to develop our risk score and the other half as a validation cohort. RESULTS From 2003 to 2015, 25 451 PNs were performed. The overall rate of major complications was 4.9%. The final risk score consisted of 10 predictors: age, sex, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, hypertension, obesity, and smoking. In the training cohort, the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval [CI] 0.73-0.78), while the AUC for the validation cohort was 0.73 (95% CI 0.70-0.75). The predicted probabilities of major complication in the low- (≤10 points), intermediate- (11-20 points), high- (21-30 points), and very high-risk (>30 points) categories were 3% (95% CI 2.6-3.2), 8% (95% CI 7.2-9.2), 24% (95% CI 20.5-27.8), and 41% (95% CI 34.5-47.8), respectively. CONCLUSIONS We developed and validated the PREP score to predict the risk of complications after PN based on patient characteristics. Calculation of the PREP score can help providers select treatment options for patients with a cT1a renal mass and enhance the informed consent process for patients planning to undergo PN.

The impact of variant histologies on overall survival (OS), as well as their influence on the response to neoadjuvant and adjuvant chemotherapy (AC) is well studied in patients diagnosed with bladder cancer. However, little is known about tumors with variant histologies of the upper urinary tract. The objective of this study was to assess the survival of the predominant variant histologies of tumors of the renal pelvis (RPT) after surgical intervention, and to examine the influence of AC on the OS of the different variant histologies. We identified 21,318 patients with RPT undergoing surgical intervention using the National Cancer Database for the period 2004–2015. We employed multivariable Cox proportional hazards regression models and Kaplan–Meier curves to evaluate the OS according to variant histology. Separate multivariable Cox regression models were used to assess the specific effect of AC on OS of the histological subgroups. The majority of patients were diagnosed with pure urothelial carcinoma (PUC) (96.1%). Overall, 826 patients were diagnosed with variant histologies (adenocarcinoma N = 298, squamous cell carcinoma N = 291, sarcomatoid N = 137, others N = 100). Compared to PUC, adenocarcinomas showed longer OS (HR 0.76, 95% confidence interval (CI) 0.62–0.94, p = 0.01), while sarcomatoid tumors had shorter OS (HR 1.59, 95% CI 1.12–2.26, p = 0.011). A subgroup analysis of patients undergoing AC showed a survival benefit in patients with PUC (HR 0.81, 95% CI 0.73–0.9, p

The prevalence of obesity is on the rise in the Unites States, and obesity has been associated with increased complications and costs in a variety of complex surgeries. However, the contribution of obesity to the overall costs of radical cystectomy has not been studied in detail using contemporary data. Our objective is to assess the variation in healthcare costs due to obesity on the index hospitalization for radical cystectomy in the United States between 2003 and 2015.This was a retrospective cohort study, using the Premier Healthcare Database, of 1,242 patients who underwent radical cystectomy and were either overweight (25 ≤ body mass index [BMI]30), obese (30 ≤ BMI40), or morbidly obese (BMI ≥ 40). The primary outcome costs of the index hospitalization for each BMI category. Multivariable median regression was used to identify drivers of increased costs.The cost of the index hospitalization for cystectomy was $24,596 (95% confidence interval [CI], $22,599-$26,592) for overweight patients. The costs for obese and morbidly obese patients were $2,158 (95% CI, -$80 to $4,395, P = 0.059) and $5,308 (95% CI, $2,652-$7,964, P0.001) higher compared to overweight patients, respectively. After adjustment for operative time or length of stay in the multivariable models, there were no longer any differences in cost. Operative time was prolonged as BMI increased (median operative time for overweight, obese, and morbidly obese: 346, 391, and 420 minutes, respectively P = 0.0001). Median length of stay was 1 day shorter for overweight vs. morbidly obese patients (P = 0.0030), with each additional day costing $1,738 (95% CI, $1,654 to $1,821, P0.0001) on multivariable analysis.The cost of radical cystectomy is greater for obese and morbidly obese patients compared to overweight patients. The increased financial cost is driven by increased operative times and longer length of stay.

711 Background: Fat-poor angiomyolipoma (AML) can be difficult to differentiate from renal cell carcinoma (RCC) radiographically and may lead to biopsy or unnecessary intervention. In vivoplatforms with the ability to identify tumor histology based on metabolic profiles may avoid unnecessary procedures & their complications. The metabolomics of AML have not been characterized, & research into this area may provide targetable molecules for large AMLs. In this study, we investigate the metabolomic profile of AMLs compared to clear cell RCC (ccRCC) using high resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Methods: Tissue samples were obtained from radical or partial nephrectomy specimens that were fresh frozen & stored at -80ºC. Tissue HRMAS MRS was performed by a Bruker AVANCE spectrometer. Metabolomic profiles of RCC & adjacent benign renal tissue were compared, and false discovery rates (FDR) accounted for multiple testing. Regions of interest (ROI) with FDR 6, 95% CI 3.27, 2.73x1012, p=0.033)in ccRCC samples. Conclusions: HRMAS MRS identified metabolites that may help differentiate fat-poor AML from ccRCC. In particular, metabolites in the 3.5-3.49 ppm spectral region increased the risk of harboring RCC. Our findings may contribute to future in vivostudies to help identify which patients require intervention for malignancy & which may be observed for benign AML without requiring biopsy.

710 Background: Renal cell carcinoma (RCC) is a metabolic disease, with the various subtypes exhibiting aberrations in different metabolic pathways. Metabolomics may offer greater sensitivity for revealing disease biology than evaluation of tissue morphology. In this study, we investigate the metabolomic profile of RCC using high resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Methods: Tissue samples were obtained from radical or partial nephrectomy specimens that were fresh frozen & stored at -80ºC. Tissue HRMAS MRS was performed by a Bruker AVANCE spectrometer. Metabolomic profiles of RCC & adjacent benign renal tissue were compared, and false discovery rates (FDR) were used to account for multiple testing. Regions of interest (ROI) with FDR < 0.05 were selected as potential predictors of malignancy. The Wilcoxon rank sum test was used to compare median MRS relative intensities for the candidate predictors. Logistic regression was used to determine odds ratios for risk of malignancy based on abundance of each metabolite. Results: There were 38 RCC (16 clear cell, 11 papillary, 11 chromophobe) & 13 adjacent normal tissue specimens (matched pairs). Metabolic predictors of malignancy based on FDR include histidine, phenylalanine, phosphocholine, serine, phosphocreatine, creatine, glycerophosphocholine, valine, glycine, myo-inositol, scylla-inositol, taurine, glutamine, spermine, acetoacetate & lactate. Higher levels of spermine, histidine & phenylalanine at 3.15-3.13 ppm were associated with a decreased risk of RCC (OR 4x10−5, 95% CI 7.42x10−8, 0.02), while 2.84-2.82 ppm increased the risk of malignant pathology (OR 7158.67, 95% CI 6.3, 8.3x106), and the specific metabolites characterizing this region remain to be identified. Tumor stage did not appear to affect the metabolomics of malignant tumors, suggesting that metabolites are more dependent on histologic subtype. Conclusions: HRMAS-MRS identified many metabolites that may predict RCC. We demonstrated that those in the 3.14-3.13 ppm ROI were present in lower levels in RCC, while higher levels of metabolites in the 2.84-2.82 ppm ROI substantially increased the risk of RCC.

Non-muscle-invasive bladder cancer (NMIBC) is a biologically heterogeneous disease and is one of the most expensive malignancies to treat on a per patient basis. In part, this high cost is attributed to the need for long-term surveillance. We sought to perform an economic analysis of surveillance strategies to elucidate cumulative costs for the management of NMIBC. A Markov model was constructed to determine the average 5-year costs for the surveillance of patients with NMIBC. Patients were stratified into low, intermediate, and high-risk groups based on the EORTC risk calculator to determine recurrence and progression rates according to each category. The index patient was a compliant 65-year-old male. A total of four health states were utilized in the Markov model: no evidence of disease, recurrence, progression and cystectomy, and death. Cumulative costs of care over a 5-year period were $52,125 for low-risk, $146,250 for intermediate-risk, and $366,143 for high-risk NMIBC. The primary driver of cost was progression to muscle-invasive disease requiring definitive therapy, contributing to 81% and 92% of overall cost for intermediate- and high-risk disease. Although low-risk tumors have a high likelihood of 5-year recurrence, the overall cost contribution of recurrence was 8%, whereas disease progression accounted for 71%. Although protracted surveillance cystoscopy contributes to the expenditures associated with NMIBC, progression increases the overall cost of care across all three patient risk groups and most notably for intermediate- and high-risk disease patients.

175 Background: The need to differentiate patients at risk for developing aggressive prostate cancer (CaP) from those at risk for less aggressive disease has led to efforts to identify genetic markers to predict disease course and personalize treatment. A study with participants from Johns Hopkins Medical Institutions (JHMI) and Washington University (WU) found single nucleotide polymorphisms (SNPs) in cell cycle genes were associated with risk of aggressive CaP. We sought to replicate those results in the European-American population of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We focused on variants associated with aggressive CaP in the JHMI and WU cohorts, which included 13 SNPs in 12 genes ( CCNC, CCND3, CCNG1, CCNT2, CDK2, CDK6, MDM2, SKP2, TERF2, WEE1, YWHAB, YWHAH). Variants were genotyped using the Pyrosequencing assay. Patients were classified into high risk (Gleason≥8, pT3b, N+, M+), low risk (Gleason≤7, ≤pT3a, N0, M0) or non-cancer control groups based on clinicopathologic characteristics. Logistic regression analysis was used to compare genotype frequencies of each variant between groups using the dominant model. Results: There were 108 aggressive and 1080 non-aggressive CaP patients, and 1155 controls . CDK6 ( rs8) was associated with increased risk of any CaP (OR 1.2, 95% CI 1.02-1.42; p = 0.032) and high risk disease (OR 1.63, 95% CI 1.09-2.42; p = 0.017) vs. controls. In contrast, the JHMI and WU cohort found CDK6 variants to be protective against aggressive CaP. CCNG1 ( rs11541970) approached significance (p = 0.052) between high risk and control groups, and CCNC conferred a protective effect consistent with the prior study, but did not reach significance (p = 0.101). No associations with any cell cycle gene variants were detected when comparing high and low risk patients. Conclusions: Our study did not replicate the results from the JHMI and WU cohorts. CDK6 predicted an increased risk of developing any CaP and high risk CaP. However, directionality was opposite to the prior study, indicating that this variant is unlikely to be a true predictor of increased risk of or protection from aggressive CaP.

434 Background: The Centers for Disease Control and Prevention estimates that nearly 40% of the U.S. population meets the criteria for obesity classification. Several studies have shown that obesity is associated with increased medical morbidity and costs. In this study, we investigated the impact of obesity on the financial burden of radical cystectomy. We hypothesize that the cost of radical cystectomy is greater in obese and morbidly obese patients compared to overweight patients. Methods: We performed a retrospective observational study within the Premier Healthcare Database (Premier Inc., Charlotte, NC), a large, U.S. hospital-based, all-payer database representing approximately 20% of annual inpatient discharges. ICD-9 procedure codes were used to identify all patients who had undergone elective radical cystectomy (57.71, 57.79) from 2003 to 2015, and administrative data was used to extract the costs associated with the index hospitalization. Patients were stratified into three body mass index (BMI) categories: overweight (25 BMI