Faculty Bibliography

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.

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.

OBJECTIVE: To assess the impact of the American Urological Association (AUA) guidelines advocating partial nephrectomy for T1 tumors guidelines on the likelihood of undergoing partial nephrectomy. MATERIALS AND METHODS: We analyzed the Nationwide Inpatient Sample (NIS), a dataset encompassing 20% of all United States inpatient hospitalizations, from 2007 through 2010. Our dependent variable was receipt of radical vs partial nephrectomy (55.50, 55.51, 55.52, and 55.54 vs 55.4) for a renal mass (International Classification of Disease, 9th Revision [ICD-9] code 189.0). The independent variable of interest was time of surgery (before or after the establishment of AUA guidelines); covariates included a diagnosis of chronic kidney disease (CKD), overall comorbidity, age, race, gender, geographic region, income, and hospital characteristics. Bivariate and multivariable adjusted logistic regression was used to determine the association between receipt of partial nephrectomy and time of guideline establishment. RESULTS: We identified 26,165 patients with renal tumors who underwent surgery. Before the guidelines, 4031 patients (27%) underwent partial nephrectomy compared to 3559 (32%) after. On multivariable analysis, undergoing surgery after the establishment of guidelines (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32, P <.01) was an independent predictor of partial nephrectomy. Other factors associated with partial nephrectomy were urban location, surgery at a teaching hospital, large hospital bed size, Northeast location, and Black race. Female gender and CKD were not associated with partial nephrectomy. CONCLUSION: Although adoption of partial nephrectomy increased after establishment of new guidelines on renal masses, partial nephrectomy remains an underutilized procedure. Future research must focus on barriers to adoption of partial nephrectomy and how to overcome them.

BACKGROUND: Reducing inappropriate use of imaging to stage incident prostate cancer is a challenging problem highlighted recently as a Physician Quality Reporting System quality measure and by the American Society of Clinical Oncology and the American Urological Association in the Choosing Wisely campaign. Since 2000, the National Prostate Cancer Register (NPCR) of Sweden has led an effort to decrease national rates of inappropriate prostate cancer imaging by disseminating utilization data along with the latest imaging guidelines to urologists in Sweden. We sought to determine the temporal and regional effects of this effort on prostate cancer imaging rates. METHODS: We performed a retrospective cohort study among men diagnosed with prostate cancer from the NPCR from 1998 to 2009 (n = 99 879). We analyzed imaging use over time stratified by clinical risk category (low, intermediate, high) and geographic region. Generalized linear models with a logit link were used to test for time trend. RESULTS: Thirty-six percent of men underwent imaging within 6 months of prostate cancer diagnosis. Overall, imaging use decreased over time, particularly in the low-risk category, among whom the imaging rate decreased from 45% to 3% (P < .001), but also in the high-risk category, among whom the rate decreased from 63% to 47% (P < .001). Despite substantial regional variation, all regions experienced clinically and statistically (P < .001) significant decreases in prostate cancer imaging. CONCLUSIONS: A Swedish effort to provide data on prostate cancer imaging use and imaging guidelines to clinicians was associated with a reduction in inappropriate imaging over a 10-year period, as well as slightly decreased appropriate imaging in high-risk patients. These results may inform current efforts to promote guideline-concordant imaging in the United States and internationally.

Whether clinical cancer research currently focuses on gaps in the evidentiary basis for clinical guidelines and/or on cancers that impose greater societal burden is unclear. This study assessed the relationship between cancer research efforts in terms of planned randomized controlled trial (RCT) enrollment, objective measures of evidence quality, and a cancer's burden on society. The authors calculated the planned RCT enrollment listed on ClinicalTrials.gov for the 17 most prevalent solid cancers. Using cancer type as the unit of analysis, linear regression was used to examine the association between planned enrollment in RCTs and 1) evidence quality, as measured by the absolute number and percent of highest quality category (category 1 [C1]) recommendations in the NCCN Clinical Practice Guidelines in Oncology for each cancer, and 2) measures of burden on society, including prevalence, incidence, person-years of life lost (PYLL), and disability-adjusted life years (DALY). Non-normal distributions were log transformed when appropriate. Overall, 15% of the NCCN recommendations were based on the highest quality evidence. Results produced 1260 RCTs. Planned RCT enrollment ranged from 2270 (testis) to 492,876 (breast) and was correlated neither with absolute number nor percent of C1 recommendations for that cancer. Planned RCT enrollment was positively correlated with a cancer's prevalence (P=.01), incidence (P<.01), PYLL (P<.01), and DALY (P<0.01). In multivariate analysis, prevalence (P<.01) and PYLL (P<.01) had the strongest association with planned RCT enrollment. Findings showed, therefore, that planned cancer RCT enrollment is associated with higher societal disease burden, not the quality of a cancer's clinical guidelines.

PURPOSE: The combination of sepsis and ureteral calculus is a urological emergency. Traditional teaching advocates urgent decompression with nephrostomy tube or ureteral stent placement, although published outcomes validating this treatment are lacking. National practice patterns for such scenarios are currently undefined. Using a retrospective study design, we defined the surgical decompression rate in patients admitted to the hospital with severe infection and ureteral calculi. We determined whether a mortality benefit is associated with this intervention. MATERIALS AND METHODS: Patient demographics and hospital characteristics were extracted from the 2007 to 2009 Nationwide Inpatient Sample. We identified 1,712 patients with ureteral calculi and sepsis. Multivariate logistic regression was performed to determine the association between mortality and surgical decompression. RESULTS: Of the patients 78% underwent surgical decompression. Mortality was higher in those not treated with surgical decompression (19.2% vs 8.82%, p <0.001). Lack of surgical decompression was independently associated with an increased OR of mortality even when adjusting for patient demographics, comorbidities and geographic region of treatment (OR 2.6, 95% CI 1.9-3.7). CONCLUSIONS: Absent surgical decompression is associated with higher odds of mortality in patients with sepsis and ureteral calculi. Further research to determine predictors of surgical decompression is necessary to ensure that all patients have access to this life saving therapy.

PURPOSE: Radical prostatectomy is a common treatment for organ confined prostate cancer and its use is increasing. We examined how the increased volume is being distributed and what hospital characteristics are associated with increasing volume. MATERIALS AND METHODS: We identified all men age 40 to less than 80 years who underwent radical prostatectomy for prostate cancer from 2000 to 2008 in the NIS (Nationwide Inpatient Sample) (586,429). Ownership of a surgical robot was determined using the 2007 AHA (American Hospital Association) Annual Survey. The association between hospital radical prostatectomy volume and hospital characteristics, including ownership of a robot, was explored using multivariate linear regression. RESULTS: From 2000 to 2008 there was a 74% increase in the number of radical prostatectomies performed (p = 0.05) along with a 19% decrease in the number of hospitals performing radical prostatectomy (p <0.001), resulting in an increase in annual hospital radical prostatectomy volume (p = 0.009). Several hospital variables were associated with greater radical prostatectomy volume including teaching status, urban location, large bed size and ownership of a robot in 2007. On multivariate analysis the year, teaching status, large bed size, urban location and presence of a robot were associated with higher hospital radical prostatectomy volume. CONCLUSIONS: Use of radical prostatectomy increased significantly between 2000 and 2008, most notably after 2005. The increase in radical prostatectomy resulted in centralization to select hospitals, particularly those in the top radical prostatectomy volume quartile and those investing in robotic technology. Our findings support the hypothesis that hospitals with the greatest volume increases are specialty centers already performing a high volume of radical prostatectomy procedures.

OBJECTIVE: Previous studies addressing racial disparities in treatment for early-stage prostate cancer have focused on the etiology of undertreatment of black men. Our objective was to determine whether racial disparities are attributable to undertreatment, overtreatment, or both. METHODS: Using the SEER-Medicare dataset, we identified men 67-84 years-old diagnosed with localized prostate cancer from 1998 to 2007. We stratified men into clinical benefit groups using tumor aggressiveness and life expectancy. Low-benefit was defined as low-risk tumors and life expectancy <10 years; high-benefit as moderate-risk tumors and life expectancy >/=10 years; all others were intermediate-benefit. Logistic regression modeled the association between race and treatment (radical prostatectomy or radiotherapy) across benefit groups. RESULTS: Of 68,817 men (9.8% black and 90.2% white), 56.2% of black and 66.3% of white men received treatment (adjusted odds ratio (OR)=0.65; 95% CI, 0.62-0.69). The percent of low-, intermediate-, and high-benefit men who received treatment was 56.7%, 68.4%, and 79.6%, respectively (P=<0.001). In the low-benefit group, 51.9% of black vs. 57.2% of white patients received treatment (OR=0.74; 95% CI, 0.67-0.81) compared to 57.2% vs. 69.6% in the intermediate-benefit group (OR=0.64; 95% CI, 0.59-0.70). Racial disparity was largest in the high-benefit group (64.2% of black vs. 81.4% of white patients received treatment; OR=0.57; 95% CI, 0.48-0.68). The interaction between race and clinical benefit was significant (P<0.001). CONCLUSION: Racial disparities were largest among men most likely to benefit from treatment. However, a substantial proportion of both black and white men with a low clinical benefit received treatment, indicating a high level of overtreatment.

PURPOSE: Intracorporeal injections have low use rates and high discontinuation rates. We examined factors associated with intracorporeal injection use, long-term satisfaction with intracorporeal injection and reasons for discontinuation in men treated with radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2003, 731 men who underwent open radical retropubic prostatectomy were enrolled in a prospective outcomes study. The 8-year followup evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection use, satisfaction and reasons for discontinuation. Logistic regression was used to determine associations between intracorporeal injection use and preoperative variables. RESULTS: The 8-year self-assessment was completed by 368 (50.4%) men. Of these men 140 (38%) indicated prior or current intracorporeal injection use, with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men were satisfied with intracorporeal injections. Reasons for discontinuation included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%) and no partner (6%). Men trying intracorporeal injections had greater preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p = 0.003). Higher preoperative sexual function scores were independently associated with the use of intracorporeal injections in a model adjusted for age, marital status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035). CONCLUSIONS: Men pursuing intracorporeal injections have better baseline erectile function and experience greater deterioration in erectile function during the early postoperative period. Despite the high efficacy of injections, many men discontinue intracorporeal injections due to dislike or discomfort. Satisfaction rates for intracorporeal injections indicate their long-term role in restoring sexual function in men with post-prostatectomy erectile dysfunction.