Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

AIMS: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1ß can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. METHODS AND RESULTS: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. CONCLUSION: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

Genetic meta-analysis of cancer diagnosis following statin use identifies new associations and implicates human leukocyte antigen (HLA) in women.

We sought to perform a genomic evaluation of the risk of incident cancer in statin users, free of cancer at study entry. Patients who previously participated in two phase IV trials (TNT and IDEAL) with genetic data were used (npooled = 11,196). A GWAS meta-analysis using Cox modeling for the prediction of incident cancer was conducted in the pooled cohort and sex-stratified. rs13210472 (near HLA-DOA gene) was associated with higher risk of incident cancer amongst women with prevalent coronary artery disease (CAD) taking statins (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.88-3.76, P = 3.5 × 10-8). Using the UK Biobank and focusing exclusively on women statin users with CAD (nfemale = 2952), rs13210472 remained significantly associated with incident cancer (HR: 1.71, 95% CI: 1.14-2.56, P = 9.0 × 10-3). The association was not observed in non-statin users. In this genetic meta-analysis, we have identified a variant in women statin users with prevalent CAD that was associated with incident cancer, possibly implicating the human leukocyte antigen pathway.

Impact of tumor, treatment, and access on outcomes in bladder cancer: Can equal access overcome race-based differences in survival?

BACKGROUND: There are race-based differences in bladder cancer survival. To better understand this phenomenon, this study was designed to assess the statistical contributions of tumor, treatment, and access variables to race-based differences in survival. METHODS: Data were extracted from the National Cancer Data Base on black and white adults with muscle-invasive bladder cancer from 2004 to 2015. The impact of tumor, access, and treatment variables on differences in survival was inferred by the performance of sequential propensity score-weighted analyses in which black and white patients were balanced with respect to demographics and health status (comorbidities) tumor characteristics, treatment, and access-related variables. The propensity score-weighted hazard of death (black vs white) was calculated after each iteration. RESULTS: This study identified 44,577 patients with a median follow-up of 77 months. After demographics and health status were balanced, black race was associated with 18% worse mortality (hazard ratio, 1.18; 95% confidence interval [CI], 1.12-1.25; P < .001). Balancing by tumor characteristics reduced this to 16%, balancing by treatment reduced this to 10%, and balancing by access-related variables resulted in no difference. Access-related variables explained 40% (95% CI, 22.9%-57.0%) of the excess risk of death in blacks, whereas treatment factors explained 35% (95% CI, 22.2%-46.9%). The contribution of tumor characteristics was not significant. CONCLUSIONS: In the models, differences in survival for black and white patients with bladder cancer are best explained by disparities in access and treatment, not tumor characteristics. Access to care is likely a key factor in racial disparities in cancer.

Quality of Care in the Treatment of Localized Intermediate and High Risk Prostate Cancer at Minority Serving Hospitals.

PURPOSE: We investigated the quality of care at minority serving hospitals compared to other institutions for men with localized intermediate and high risk prostate cancer. MATERIALS AND METHODS: Using the National Cancer Database we identified 536,539 men 40 years old or older who presented with localized intermediate and high risk prostate cancer in the United States between 2004 and 2015. Institutions were ranked according to the proportion of black and Hispanic patients treated at a given institution, and the top decile institutions were defined as minority serving hospitals. We used multivariable analyses to characterize the association between minority serving hospitals and 3 end points, including receipt of definitive treatment, time to definitive treatment and receipt of androgen deprivation therapy in young (65 years or younger) and healthy (no comorbidity) men treated with external beam radiation therapy. RESULTS: A total of 162 and 1,168 hospitals were defined as minority and nonminority serving hospitals, respectively. On multivariable analyses treatment at minority serving hospitals was associated with decreased odds of receiving definitive treatment (adjusted OR 0.73, 95% CI 0.62-0.85, p <0.001). Adjusted mean ± SE time to treatment was significantly longer at minority serving hospitals compared to nonminority serving hospitals (4.9 ± 2.2 days, p = 0.024). Among young and healthy men there was no association between treatment at a minority serving hospital and receipt of androgen deprivation therapy in conjunction with external beam radiation (AOR 0.90, 95% CI 0.75-1.09, p = 0.291). CONCLUSIONS: Treatment at a minority serving hospital was associated with lower odds of receiving definitive therapy and longer time to definitive therapy for localized intermediate and high risk prostate cancer despite adjustment for race. This suggests that some racial disparities in prostate cancer may be explained by the sites at which racial and/or ethnic minorities receive care.

Neoadjuvant Androgen Deprivation Therapy Prior to Radical Prostatectomy: Recent Trends in Utilization and Association with Postoperative Surgical Margin Status.

PURPOSE: In this study, we sought to describe the contemporary trends in utilization of neoadjuvant androgen deprivation therapy (ADT). As a secondary endpoint, we assessed the community-level effect of neoadjuvant ADT on positive surgical margins after radical prostatectomy (RP). METHODS: Using the National Cancer Database (2004-2014), we identified patients with clinically localized prostate cancer (PCa) [cT1-4N0M0] treated with RP. The estimated annual percentage change (EAPC) mixed linear regression methodology was used for temporal trend analysis of neoadjuvant ADT. Observed differences in baseline characteristics between patients treated with neoadjuvant ADT versus those who were not were then controlled for using an inverse probability of treatment weighting (IPTW) approach. IPTW-adjusted analyses were then performed to examine the odds of positive surgical margins. RESULTS: Overall, 8184 (2.12%) and 377,843 (97.88%) individuals with PCa were treated with neoadjuvant ADT prior to RP versus RP only, respectively. There was a consistent trend in decreasing use of neoadjuvant ADT over time, with a nadir observed in 2011 [EAPC - 8.08; 95% confidence interval (CI) - 11.7 to - 4.32; p < 0.05]. In IPTW-adjusted analyses, the odds of positive surgical margins were lower in patients receiving neoadjuvant ADT with low-risk [odds ratio (OR) 0.65; 95% CI 0.51-0.84; p < 0.001] and intermediate-risk [OR 0.76; 95% CI 0.69-0.85; p < 0.001] PCa. CONCLUSIONS: After a period of steady decline, there appears to be a modest trend towards increased utilization of neoadjuvant ADT in more recent years. We found an association between neoadjuvant ADT and decreased odds of positive surgical margins among low- and intermediate-risk patients.

Comparing the Association Between Insurance and Mortality in Ovarian, Pancreatic, Lung, Colorectal, Prostate, and Breast Cancers.

BACKGROUND: Insurance coverage is associated with better cancer outcomes; however, the relative importance of insurance coverage may differ between cancers. This study compared the association between insurance coverage at diagnosis and cancer-specific mortality (CSM; insurance sensitivity) in 6 cancers. PATIENTS AND METHODS: Using the SEER cancer registry, data were abstracted for individuals diagnosed with ovarian, pancreatic, lung, colorectal, prostate, or breast cancer in 2007 through 2010. The association between insurance coverage at diagnosis and CSM was modeled using a Fine and Gray competing-risks regression adjusted for demographics. An interaction term combining insurance status and cancer type was used to test whether insurance sensitivity differed between cancers. Separate models were fit for each cancer. To control for lead-time bias and to assess whether insurance sensitivity may be mediated by earlier diagnosis and treatment, additional models were fit adjusting for disease stage and treatment. RESULTS: Lack of insurance was associated with an increased hazard of CSM in all cancers (P<.01). The magnitude of the effect differed significantly between cancers (Pinteraction=.04), ranging from an adjusted hazard ratio of 1.13 (95% CI, 1.01-1.28) in ovarian and 1.19 (95% CI, 1.11-1.29) in pancreatic cancer to 2.19 (95% CI, 2.02-2.37) in breast and 2.98 (95% CI, 2.54-3.49) in prostate cancer. The benefit of insurance was attenuated after adjusting for stage and treatment (eg, screening/early treatment effect), with the largest reductions in prostate, breast, and colorectal cancers. CONCLUSIONS: Greater insurance sensitivity was seen in screening-detected malignancies with effective treatments for early-stage disease (eg, prostate, breast, and colorectal cancers). Given that this differential is significantly reduced after adjusting for stage and treatment, our results suggest that a significant portion (but not all) of the benefit of insurance coverage is due to detection and treatment of certain curable early-stage cancers.

Reassessing the value of high-volume cancer care in the era of precision medicine.

The ethical and economic discussions regarding the extreme costs of many new cancer therapies are familiar. The authors have long held that changes in cancer care delivery also are an important strategy, yielding large benefits at potentially far lower costs. To put this into context, the authors performed an analysis to compare the overall survival of patients receiving a complex oncologic surgery, radical cystectomy, at high-volume and low-volume centers. Propensity score weighting was performed to simulate random allocation into high-volume versus low-volume centers, as would be the case in a prospective trial. On average, patients undergoing surgery at high-volume centers survived 15 months longer than those treated at low-volume centers (57.0 months vs 41.8 months). Although there certainly are caveats in contrasting the survival benefit of different care settings with anticancer agents, this differential clearly rivals or exceeds the benefit of many expensive, recently approved agents. As the debate regarding the costs of cancer therapies continues, it is worth remembering that investments in simple systems-based changes to improve cancer care delivery remain an important and likely cost-effective strategy with which to improve the survival of patients with cancer. Cancer 2018;124:1319-21. © 2018 American Cancer Society.

Variation in the use of active surveillance for low-risk prostate cancer.

BACKGROUND: This study assessed the use of active surveillance in men with low-risk prostate cancer and evaluated institutional factors associated with the receipt of active surveillance. METHODS: A retrospective, hospital-based cohort of 115,208 men with low-risk prostate cancer diagnosed between 2010 and 2014 was used. Multivariate and mixed effects models were used to examine variation and factors associated with active surveillance. RESULTS: During the study period, the use of active surveillance increased from 6.8% in 2010 to 19.9% in 2014 (estimated annual percentage change, +28.8%; 95% confidence interval [CI], + 19.6% to + 38.7%; P = .002). The adjusted probability of active-surveillance receipt by institution was highly variable. Compared with patients treated at comprehensive community cancer centers, patients treated at community cancer programs (odds ratio [OR], 2.00; 95% CI, 1.50-2.67; P < .001) and academic institutions (OR, 2.47; 95%, CI, 1.81-3.37; P < .001) had higher odds of receiving active surveillance. Compared with patients treated at very low-volume facilities, patients treated at very high-volume facilities had higher odds of receiving active surveillance (OR, 3.57; 95% CI, 1.94-6.55; P < .001). Patient and hospital characteristics accounted for 60.2% of the overall variation, whereas the treating institution accounted for 91.5% of the unexplained variability. CONCLUSIONS: Within this hospital-based cohort, the use of active surveillance for low-risk prostate cancer increased significantly over time. Significant variation was found in the use of active surveillance. Most of the variation was attributable to facility-related factors such as the facility type, facility volume, and institution. Policies to achieve consistent and higher rates of active surveillance, when appropriate, should be a priority of professional societies and patient advocacy groups. Cancer 2018;124:55-64. © 2017 American Cancer Society.

Cognitive Impairment in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: Use of androgen deprivation therapy may increase the risk of cognitive impairment in men with prostate cancer. We performed a systematic review of the risk of overall cognitive impairment as an outcome in men receiving androgen deprivation therapy for prostate cancer. MATERIALS AND METHODS: Studies were identified through PubMed®, MEDLINE®, PsycINFO®, Cochrane Library and Web of Knowledge/Science™. Articles were included if they 1) were published in English, 2) had subjects treated for prostate cancer with androgen deprivation therapy, 3) incorporated longitudinal comparisons and 4) used control groups. In addition, prospective studies were required to assess an established cognitive related end point using International Cognition and Cancer Task Force criteria defining impaired cognitive performance as scoring 1.5 or more standard deviations below published norms on 2 or more tests, or scoring 2.0 or more standard deviations below published norms on at least 1 test. The effect of androgen deprivation therapy on cognitive impairment was pooled using a random effects model. RESULTS: Of 221 abstracts 26 were selected for full text review, and 2 prospective and 4 retrospective studies were analyzed. Androgen deprivation therapy was not associated with overall cognitive impairment when the prospective cohort studies were pooled (OR 1.57, 95% CI 0.50 to 4.92, p = 0.44) with significant heterogeneity between estimates (I2 = 83%). In retrospective data the relative risk of any cognitive impairment, including senile dementia and Alzheimer disease, was increased in men receiving androgen deprivation therapy, although the difference was not statistically significant (HR 1.28, 95% CI 0.93 to 1.76, p = 0.13) with moderate heterogeneity between estimates (I2 = 67%). CONCLUSIONS: Analyses between overall cognitive impairment and use of androgen deprivation therapy defined according to International Cognition and Cancer Task Force criteria in a pooled analysis were inconclusive. In retrospective cohort studies the risk of overall cognitive impairment after androgen deprivation therapy was not significant. Better prospective studies need to be designed for the assessment of this end point.

Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer.

PURPOSE: Androgen deprivation therapy is associated with the development of diabetes and metabolic syndrome. To our knowledge its effect on the development of nonalcoholic fatty liver disease, a condition which frequently co-occurs with metabolic syndrome and other subsequent liver conditions such as liver cirrhosis, hepatic necrosis or any liver disease, has not been investigated. MATERIALS AND METHODS: We identified 82,938 men 66 years old or older who were diagnosed with localized prostate cancer in the SEER (Surveillance, Epidemiology and End Results)-Medicare database from 1992 to 2009. Men with preexisting nonalcoholic fatty liver disease, liver disease, diabetes or metabolic syndrome were excluded from study. Propensity score adjusted, competing risk regression models were created to compare the risk of nonalcoholic fatty liver disease in men who were vs were not treated with androgen deprivation. We also explored the influence of cumulative exposure to androgen deprivation therapy, calculated as monthly equivalent doses of gonadotropin-releasing hormone agonists/antagonists (fewer than 7, 7 to 11 or more than 11 doses). RESULTS: Overall 37.5% of men underwent androgen deprivation therapy. They were more likely to be diagnosed with nonalcoholic fatty liver disease (HR 1.54, 95% CI 1.40-1.68), liver cirrhosis (HR 1.35, 95% CI 1.12-1.60), liver necrosis (HR 1.41, 95% CI 1.15-1.72) and any liver disease (HR 1.47, 95% CI 1.35-1.60). A dose-response relationship was observed between the number of androgen deprivation therapy doses, and nonalcoholic fatty liver disease and any liver disease. CONCLUSIONS: Androgen deprivation therapy in men with prostate cancer is associated with the diagnosis of nonalcoholic fatty liver disease. The usual limitations of an observational study design apply, including possible inaccuracy in defining outcomes in a population based registry.

Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men.

OBJECTIVES: To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA). METHODS: A cohort of 3 422 male US military service members, retirees and their dependents, aged 40-64 years, was identified, who were prescribed TRT between 2006 and 2010 for low testosterone levels. The men in this cohort were matched on a 1:1 basis for age and comorbidities to men without a prescription for TRT. Event-free survival and rates of thromboembolism, cardiovascular events and OSA were compared between men using TRT and the control group, with a median follow-up of 17 months. RESULTS: There was no difference in event-free survival with regard to thromboembolism (P = 0.239). Relative to controls, men using TRT had improved cardiovascular event-free survival (P = 0.004), mainly as a result of lower incidence of coronary artery disease (P = 0.008). The risk of OSA was higher in TRT users (2-year risk 16.5% [95% confidence interval 15.1-18.1] in the TRT group vs 12.7% [11.4-14.1] in the control group. CONCLUSIONS: This study adds to growing evidence that the cardiovascular risk associated with TRT may be lower than once feared. The elevated risk of OSA in men using TRT is noteworthy.

Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era.

INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the "pre-immunotherapy era") and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC. RESULTS: There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013. CONCLUSION: Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

BACKGROUND: Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. METHODS: Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. RESULTS: Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). CONCLUSIONS: Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society.

Morbidity and Mortality of Locally Advanced Prostate Cancer: A Population Based Analysis Comparing Radical Prostatectomy versus External Beam Radiation.

PURPOSE: The management of locally advanced prostate cancer remains controversial. We compared the effect of primary external beam radiation therapy vs radical prostatectomy for locally advanced prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed the records of 2,935 elderly men 65 years old or older in the SEER (Surveillance, Epidemiology and End Results)-Medicare linked database who underwent external beam radiation therapy or radical prostatectomy for locally advanced prostate cancer. Propensity adjusted Cox proportional hazard and regression models were fit to examine urinary and gastrointestinal toxicities, the use of androgen deprivation therapy, and overall and prostate cancer specific mortality. RESULTS: A total of 1,429 men (48.69%) underwent radical prostatectomy and had a median followup of 11.47 years (IQR 6.17-17.17) years. A total of 1,506 men (51.31%) received external beam radiation therapy and had a median followup of 7.04 years (IQR 4.11-10.51, p <0.001). Patients treated with radical prostatectomy were at significantly higher risk for urinary and sexual toxicities (HR 1.93, 95% CI 1.66-2.24 and HR 5.50, 95% CI 3.59-8.42, respectively). However, they were at lower risk for gastrointestinal toxicities (HR 0.75, 95% CI 0.65-0.86) than those treated with external beam radiation therapy. Radical prostatectomy was associated with lower odds of androgen deprivation therapy 5 years after primary treatment (OR 0.53, 95% CI 0.41-0.69, p <0.001). External beam radiation therapy was associated with higher overall and prostate specific mortality (HR 1.41, 95% CI 1.09-1.82 and HR 2.35, 95% CI 1.85-2.98, respectively). CONCLUSIONS: We found significant toxicity and survival differences in elderly men who underwent primary external beam radiation therapy vs radical prostatectomy for locally advanced prostate cancer. While our findings must be interpreted within the limitations of studies that rely on administrative claims, they may yet help tailor individual therapies for elderly men who present with locally advanced prostate cancer.

The Use of Prostate Specific Antigen Screening in Purchased versus Direct Care Settings: Data from the TRICARE® Military Database.

PURPOSE: Fee for service reimbursement incentives may affect care. We compared the odds of prostate specific antigen screening among former and active duty United States military service members based on receipt of primary care from integrated military health facilities vs community providers reimbursed via fee for service. MATERIALS AND METHODS: We retrospectively studied the records of all active duty and retired male service members 40 to 64 years old who were covered by the TRICARE® military health benefit in 2010. Beneficiaries may receive primary care at military run facilities via the direct care system or with private physicians via the purchased care system. We compared rates of prostate specific antigen screening between propensity score weighted cohorts of 219,290 men who received primary care in the direct care system and 177,748 who received it in the purchased care system. RESULTS: The screening rate was 35% in the direct care system vs 26% in the purchased care system. After propensity score weighting the former men were significantly more likely to undergo prostate specific antigen screening than men who received primary care in the purchased care system (adjusted OR 1.76, 95% CI 1.729-1.781). Age older than 52 years, rank and black race were associated with increased odds of prostate specific antigen screening in each cohort. CONCLUSIONS: These results suggest that salaried primary care providers employed at integrated military facilities are more likely to order prostate specific antigen screening compared to those reimbursed in a fee for service fashion by military insurance. Growing understanding of how fee for service incentives impact prostate specific antigen screening by primary care providers may enable advocates and policy makers to leverage reimbursement systems as a tool to change prostate cancer screening.

Role of survivin expression in predicting biochemical recurrence after radical prostatectomy: a multi-institutional study.

OBJECTIVE: To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models. RESULTS: Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin. CONCLUSIONS: Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making.

Accountable care organizations and the use of cancer screening.

Cancer preventive services, when used appropriately, result in improved health, better quality of life and decreased costs. For these reasons, cancer preventive services represent important priorities within the Affordable Care Act (ACA). Among the many provisions to improve access to preventive services the ACA introduced Accountable Care Organizations (ACOs) as trajectory to deliver coordinated, high-quality care. In order to evaluate this benchmark, we analyzed (in 2016/Boston) screening prevalence of breast cancer, a recommended screening test according to the United States Preventive Services Task Force (USPSTF), and prostate cancer, for which screening is no longer recommended by the USPSTF, among traditional Medicare beneficiaries and those enrolled in ACOs. We used propensity-score weighting to adjust for baseline confounders. We found that the prevalence of breast cancer screening (35.0% vs. 25.2%, p<0.001) and prostate cancer screening (54.6% vs. 41.7%, p<0.001) is higher among ACO enrollees. Our results suggest increased utilization of cancer preventive care within ACOs, regardless of whether the test is recommended or not. Better efforts may be needed within the ACO infrastructure to encourage recommended preventive care, but also penalize unnecessary use of low value services.

Recurrence in Localized Renal Cell Carcinoma: a Systematic Review of Contemporary Data.

PURPOSE OF REVIEW: Patients with localized renal cell carcinoma (RCC) are at risk of recurrence. The purpose of this review was to characterize the literature on recurrence rates and risk factors after diagnosis of localized RCC. RECENT FINDINGS: Our search revealed that existing data examining the prevalence of recurrence rates predominantly originates from cohorts of patients diagnosed and treated in the 1980s to 1990s, and may therefore not be as useful for counseling for current patients today. Many nomograms including the Cindolo Recurrence Risk Formula, the University of California-Los Angeles (UCLA) Integrated Scoring System (UISS), the SSIGN score, the Kattan nomogram, and the Karakiewicz nomogram have shown value in identifying patients at higher risk for recurrence. Biomarkers and gene assays have shown promise in augmenting the predictive accuracy of some of the aforementioned predictive models, especially when multiple gene markers are used in combination. However, more work is needed in not only developing a model but also validating it in other settings prior to clinical use. Adjuvant therapy is a promising new treatment strategy for patients with high-risk disease. Importantly, too many surveillance strategies exist. This may stem from the lack of a consensus in the urological community in how to follow these patients, as well as the variable guideline recommendations. In conclusion, contemporary recurrence rates are needed. Recurrence risk prediction models should be developed based on a series of more contemporary patients, and externally validated prior to routine clinical practice. Surveillance strategies following treatment of localized RCC need to be identified and standardized. Finally, there is a trend toward personalizing surveillance regimens to more appropriately screen patients at higher risk of recurrence.

Differences in Patient Characteristics among Men Choosing Open or Robot-Assisted Radical Prostatectomy in Contemporary Practice - Analysis of Surveillance, Epidemiology, and End Results Database.

OBJECTIVE: To examine characteristics of robot-assisted (RARP) and open radical prostatectomy (ORP) patients. PATIENTS AND METHODS: We relied on the Surveillance, Epidemiology, and End Results-Medicare-linked database and focused on prostate cancer patients between 2008 and 2009. In multivariable logistic regression analyses, we predicted RARP. RESULTS: Of 5,915 patients, 3,476 (58.8%) underwent RARP and 2,439 (41.2%) ORP. Patients within intermediate (OR 1.4, p = 0.01) or highest (OR 1.5, p = 0.02) education strata and those treated by surgeons with a high volume (OR 2.2, p < 0.001) were more likely to undergo RARP. Conversely, those residing in rural areas (OR 0.7, p = 0.005) and those with clinical stage T2 or higher (OR 0.7, p = 0.006) were less likely to undergo RARP. Additionally, patients from the Southwest were less likely to undergo RARP (OR 0.4, p < 0.001), but those from the Northern Plains were more likely to undergo RARP (OR 1.4, p = 0.02) than their counterparts from the East. Finally, RARP patients were neither younger nor healthier than ORP patients. CONCLUSIONS: Several patient characteristics such as education, region of residence and population density affect the likelihood of RARP vs. ORP treatment. Similarly, clinical stage and surgeon characteristics also affect the assignment to one or other treatment modality.

External Validation of Bladder Cancer Predictive Nomograms for Recurrence, Cancer-Free Survival and Overall Survival following Radical Cystectomy.

PURPOSE: We externally validated 3 previously published nomograms to predicting recurrence, and cancer specific and overall survival following radical cystectomy and pelvic lymph node dissection for urothelial carcinoma of the bladder. MATERIALS AND METHODS: Two surgeons from a single institution performed a total of 197 consecutive radical cystectomies and pelvic lymph node dissections for bladder cancer from January 2003 to September 2009. A total of 23 patients were excluded from analysis. Examined parameters were those used in the original nomograms, including patient age, gender, pathological T stage, N stage, tumor grade, presence of carcinoma in situ and lymphovascular invasion, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiation therapy. Nomogram predictions were compared to actuarial outcomes and predictive accuracy was quantified using measures of discrimination and calibration. RESULTS: At the time of analysis 34 patients had experienced recurrence, of whom 28 died of disease and 6 were currently alive with disease. Discrimination at 2, 5 and 8 years was 0.776, 0.809 and 0.794 for recurrence, 0.822, 0.840 and 0.849 for cancer specific survival, and 0.812, 0.820 and 0.825, respectively, for overall survival. Calibration plots revealed nomogram overestimation of all 3 end points. CONCLUSIONS: Nomograms for bladder cancer recurrence, cancer specific survival and overall survival following radical cystectomy and pelvic lymph node dissection performed well in our series with accuracy comparable to that in the original series. The use of nomogram predictions should be further explored in clinical trials to assess the impact on patient care in clinical practice.