Faculty Bibliography

INTRODUCTION: The rapid diffusion of the surgical robot has been controversial because of the technology's high costs and its disputed marginal benefit. Some, however, have suggested that adoption of the robot may have improved care for patients with renal malignancy by facilitating partial nephrectomy, an underutilized, technically challenging procedure believed to be less morbid than radical nephrectomy. We sought to determine whether institutional acquisition of the robot was associated with increased utilization of partial nephrectomy. METHODS:: We used all payer data from 7 states to identify 21,569 nephrectomies. These patient-level records were aggregated to the hospital-level then merged with the American Hospital Association Annual Survey and publicly available data on timing of robot acquisition. We used a multivariable difference-in-difference model to assess at the hospital-level whether robot acquisition was associated with an increase in the proportion of partial nephrectomy, adjusting for hospital nephrectomy volume, year of surgery, and several additional hospital-level factors. RESULTS:: In the multivariable-adjusted differences-in-differences model, hospitals acquiring a robot between 2001 and 2004 performed a greater proportion of partial nephrectomy in both 2005 (29.9% increase) and 2008 (34.9% increase). Hospitals acquiring a robot between 2005 and 2008 also demonstrated a greater proportion of partial nephrectomy in 2008 (15.5% increase). In addition, hospital nephrectomy volume and urban location were also significantly associated with increased proportion of partial nephrectomy. CONCLUSIONS:: Hospital acquisition of the surgical robot is associated with greater proportion of partial nephrectomy, an underutilized, guideline-encouraged procedure. This is one of the few studies to suggest robot acquisition is associated with improvement in quality of patient care.

OBJECTIVE: To examine public and media response to the United States Preventive Services Task Force's (USPSTF) draft (October 2011) and finalized (May 2012) recommendations against prostate-specific antigen (PSA) testing using Twitter, a popular social network with over 200 million active users. MATERIALS AND METHODS: We used a mixed methods design to analyze posts on Twitter, called "tweets." Using the search term "prostate cancer," we archived tweets in the 24 hour periods following the release of the USPSTF draft and finalized recommendations. We recorded tweet rate per hour and developed a coding system to assess type of user and sentiment expressed in tweets and linked articles. RESULTS: After the draft and finalized recommendations, 2042 and 5357 tweets focused on the USPSTF report, respectively. Tweet rate nearly doubled within two hours of both announcements. Fewer than 10% of tweets expressed an opinion about screening, and the majority of these were pro-screening during both periods. In contrast, anti-screening articles were tweeted more frequently in both draft and finalized study periods. From the draft to the finalized recommendations, the proportion of anti-screening tweets and anti-screening article links increased (p= 0.03 and p<0.01, respectively). CONCLUSIONS: There was increased Twitter activity surrounding the USPSTF draft and finalized recommendations. The percentage of anti-screening tweets and articles appeared to increase, perhaps due to the interval public comment period. Despite this, most tweets did not express an opinion, suggesting a missed opportunity in this important arena for advocacy.

BACKGROUND: The surgical robot has been widely adopted in the United States in spite of its high cost and controversy surrounding its benefit. Some have suggested that a "medical arms race" influences technology adoption. We wanted to determine whether a hospital would acquire a surgical robot if its nearest neighboring hospital already owned one. METHODS: We identified 554 hospitals performing radical prostatectomy from the Healthcare Cost and Utilization Project Statewide Inpatient Databases for seven states. We used publicly available data from the website of the surgical robot's sole manufacturer (Intuitive Surgical, Sunnyvale, CA) combined with data collected from the hospitals to ascertain the timing of robot acquisition during year 2001 to 2008. One hundred thirty four hospitals (24%) had acquired a surgical robot by the end of 2008. We geocoded the address of each hospital and determined a hospital's likelihood to acquire a surgical robot based on whether its nearest neighbor owned a surgical robot. We developed a Markov chain method to model the acquisition process spatially and temporally and quantified the "neighborhood effect" on the acquisition of the surgical robot while adjusting simultaneously for known confounders. RESULTS: After adjusting for hospital teaching status, surgical volume, urban status and number of hospital beds, the Markov chain analysis demonstrated that a hospital whose nearest neighbor had acquired a surgical robot had a higher likelihood itself acquiring a surgical robot. (OR=1.71, 95% CI: 1.07-2.72, p=0.02). CONCLUSION: There is a significant spatial and temporal association for hospitals acquiring surgical robots during the study period. Hospitals were more likely to acquire a surgical robot during the robot's early adoption phase if their nearest neighbor had already done so.

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.

BACKGROUND: Cancer continues to rise as a contributor to premature death in the developing world. Despite this, little is known about whether cancer outcomes are related to a country's income level, and what aspects of national healthcare systems are associated with improved cancer outcomes. METHODS: The most recent estimates of cancer incidence and mortality were used to calculate mortality-to-incidence ratio (MIR) for the 85 countries with reliable data. Countries were categorized according to high-income (Gross Domestic Product (GDP)>$15,000) or middle/low-income (GDP<$15,000), and a multivariate linear regression model was used to determine the association between healthcare system indicators and cancer MIR. Indicators study included per capita GDP, overall total healthcare expenditure (THE), THE as a proportion of GDP, total external beam radiotherapy devices (TEBD) per capita, physician density, and the year 2000 WHO healthcare system rankings. RESULTS: Cancer MIR in high-income countries (0.47) was significantly lower than that of middle/low-income countries (0.64), with a p<0.001. In high-income countries, GDP, health expenditure and TEBD showed significant inverse correlations with overall cancer MIR. A $3040 increase in GDP (p=0.004), a $379 increase in THE (p<0.001), or an increase of 0.59 TEBD per 100,000 population (p=0.027) were all associated with a 0.01 decrease in cancer MIR. In middle/low-income countries, only WHO scores correlated with decreased cancer MIR (p=0.022); 12 specific cancer types also showed similar significant correlations (p<0.05) as overall cancer MIR. CONCLUSIONS: The analysis of this study suggested that cancer MIR is greater in middle/low-income countries. Furthermore, the WHO healthcare score was associated with improved cancer outcomes in middle/low-income countries while absolute levels of financial resources and infrastructure played a more important role in high-income countries.

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17mug/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80 (95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49mug/l and 10.87 to 47.49mug/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36 (95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17mug/l and >41.17mug/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.

BACKGROUND: Recent debate about prostate-specific antigen (PSA)-based testing for prostate cancer screening among older men has rarely considered the cost of screening. METHODS: A population-based cohort of male Medicare beneficiaries aged 66 to 99 years, who had never been diagnosed with prostate cancer at the end of 2006 (n = 94,652), was assembled, and they were followed for 3 years to assess the cost of PSA screening and downstream procedures (biopsy, pathologic analysis, and hospitalization due to biopsy complications) at both the national and the hospital referral region (HRR) level. RESULTS: Approximately 51.2% of men received PSA screening tests during the 3-year period, with 2.9% undergoing biopsy. The annual expenditures on prostate cancer screening by the national fee-for-service Medicare program were $447 million in 2009 US dollars. The mean annual screening cost at the HRR level ranged from $17 to $62 per beneficiary. Downstream biopsy-related procedures accounted for 72% of the overall screening costs and varied significantly across regions. Compared with men residing in HRRs that were in the lowest quartile for screening expenditures, men living in the highest HRR quartile were significantly more likely to be diagnosed with prostate cancer of any stage (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] = 1.07-1.35) and localized cancer (IRR = 1.30, 95% CI = 1.15-1.47). The IRR for regional/metastasized cancer was also elevated, although not statistically significant (IRR = 1.31, 95% CI = 0.81-2.11). CONCLUSIONS: Medicare prostate cancer screening-related expenditures are substantial, vary considerably across regions, and are positively associated with rates of cancer diagnosis. Cancer 2014;120:96-102. (c) 2013 American Cancer Society.

PURPOSE: The prevalence of lower urinary tract symptoms increases with age and impairs quality of life. Radical prostatectomy has been shown to relieve lower urinary tract symptoms at short-term followup but the long-term effect of radical prostatectomy on lower urinary tract symptoms is unclear. MATERIALS AND METHODS: We performed a prospective cohort study of 1,788 men undergoing radical prostatectomy. The progression of scores from the self-administered AUASS (American Urological Association symptom score) preoperatively, and at 3, 6, 12, 24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for preoperative AUASS, age, prostate specific antigen, pathological Gleason score and stage, nerve sparing, race and marital status. This model was also applied to patients stratified by baseline clinically significant (AUASS greater than 7) and insignificant (AUASS 7 or less) lower urinary tract symptoms. RESULTS: Men exhibited an immediate worsening of lower urinary tract symptoms that improved between 3 months and 2 years after radical prostatectomy. Overall the difference between mean AUASS at baseline and at 10 years was not statistically or clinically significant. Men with baseline clinically significant lower urinary tract symptoms experienced immediate improvements in lower urinary tract symptoms that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001). Men with baseline clinically insignificant lower urinary tract symptoms experienced a statistically significant but clinically insignificant increase in mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with clinically significant lower urinary tract symptoms decreased from baseline to 10 years after radical prostatectomy (p = 0.02). CONCLUSIONS: Radical prostatectomy is the only treatment for prostate cancer shown to improve and prevent the development of lower urinary tract symptoms at long-term followup. This previously unrecognized long-term benefit argues in favor of the prostate as the primary contributor to male lower urinary tract symptoms.

Prostate cancer is a leading cause of cancer death in men in developed countries. While early stage disease can often be cured, many patients eventually develop castration resistant prostate cancer (CRPC). The majority of CRPC patients have bone metastases, which cause significant morbidity and mortality. Although there is no cure for prostate cancer metastatic to bone, several bone-targeted agents have been approved to prevent skeletal-related events (SREs). Among them, bisphosphonates were the first class of drugs investigated for prevention of SREs. Denosumab is a recently approved agent that binds to the receptor activator of nuclear factor-kappaB ligand (RANKL) as a humanized monoclonal antibody. Both agents target prostate cancer skeletal metastasis through the inhibition of bone resorption. Alpharadin is the first radiopharmaceutical agent that has significant overall survival benefit. It has benefits in pain palliation and SREs as well. Another newly approved drug is Abiraterone acetate, which decreases circulating levels of testosterone by targeting an enzyme expressed in the testis and the adrenal, as well as in prostate cancer tissues. This review outlines the clinical and preclinical data supporting the use of these and new agents in development for CRPC with bone metastasis.