Risk of Severe COVID-19 in Prevalent Users of Alpha-1 Adrenergic Receptor Antagonists: A National Case-Control Study of Medicare Beneficiaries.

BACKGROUND: Alpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure. METHODS: We performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: There were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18). CONCLUSIONS: Prevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19.

Utilization of hydroxyprogesterone caproate among pregnancies with live birth deliveries in the sentinel distributed database.

BACKGROUND: The U.S. Food and Drug Administration (FDA) approved Makena® (hydroxyprogesterone caproate [HPC] injection) in February 2011 for reducing the risk of preterm birth (PTB) in women with a singleton pregnancy who had a history of singleton spontaneous PTB (sPTB). Makena was approved under accelerated approval and required a postmarketing study to verify its clinical benefits. However, the postmarketing trial (PROLONG) failed to verify Makena's clinical benefit to neonates and substantiate its effect on reducing the risk of recurrent PTB. This study examined the utilization of HPC, along with another progestogen (vaginal progesterone) used to reduce the risk of sPTB during pregnancy, to inform the landscape of HPC use in the United States. METHODS: We included pregnant women aged 10-54 years with a live birth delivery from 1 January, 2008 to 31 December, 2018 in the Sentinel Distributed Database (SDD). We examined the prevalence of injectable HPC (Makena and its generics), compounded HPC, and vaginal progesterone use during the second and third trimesters during the study period. We also assessed the proportion of these HPC-exposed pregnancies with obstetrical conditions of interest as potential reasons for use: (1) history of preterm delivery; (2) cervical shortening in the current pregnancy; and (3) preterm labor in the current pregnancy. RESULTS: We identified a total of 3,445,739 live-birth pregnancies (among 2.9 million women) between 2008 and 2018 in the SDD. Of these pregnancies, 6.5 per 1,000 pregnancies used injectable HPC, 2.3 per 1,000 pregnancies used compounded HPC, and 1.5 per 1,000 pregnancies used vaginal progesterone during the second and/or third trimesters. The yearly uptakeof pregnancies with injectable HPC use increased during the study period from 2.1 per 1,000 pregnancies in 2012 to 12.6 per 1,000 pregnancies in 2018; use of compounded HPC decreased from 3.3 per 1,000 pregnancies to 0.25 per 1,000 pregnancies over the same period. Of 16,524 pregnancies with injectable HPC use, 12,054 (73%) had at least one related obstetrical condition, including 6,439 (39%) with a recorded history of preterm delivery. In addition, 4,665 (28%) had a PTB recorded as the outcome for the current pregnancy. CONCLUSIONS: We found modest use of HPC during the second and/or third trimesters among all live-birth pregnancies in SDD. The majority of pregnancies with injectable HPC use had at least one of three obstetrical indications of interest recorded before or during the pregnancy.

Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink.

OBJECTIVE: To evaluate the association between statin use and risk of biliary tract cancers (BTC). DESIGN: This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders. RESULTS: We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007). CONCLUSION: Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.

Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study.

BACKGROUND: As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD). METHODS: We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors. RESULTS: Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD. CONCLUSIONS: In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.

Utilization and predictors of expectant management among elderly men with low-and intermediate-risk localized prostate cancer in U.S. urological practice.

INTRODUCTION: Expectant management (EM) reduces overtreatment in low-risk but not intermediate-risk localized prostate cancer (PCa). We assessed the use and predictors of EM to understand its uptake in U.S. practice. METHODS: Using the U.S. SEER-Medicare database, we conducted a retrospective cohort study of men 66 years and older diagnosed with low-risk (N=25,506) or intermediate-risk (N=25,597) localized PCa between 2004 - 2011 and followed through December 31, 2012. We defined EM as no definitive therapy (DT) and at least one prostate-specific antigen (PSA) test or re-biopsy 4 - 12 months post diagnosis; or receiving DT after PSA testing or re-biopsy 7 - 12 months after diagnosis. We performed separate analyses for low-risk and intermediate-risk groups using multiple logistic regressions. RESULTS: For men diagnosed with PCa in 2004-2011, EM increased from 22% to 43% in the low-risk group and from 15% to 18% in the intermediate-risk group. In the low-risk group, EM increased with patients' age (adjusted odds ratio [aOR] = 1.26 for 71-75 years; 2.21 for 76-80 years; 6.33 for older then 80, p<0.0001, compared to 66-70 years). EM uptake was higher among men with comorbidities (aOR=1.29), and residing in the Pacific region (aOR=0.56, compared to the East Coast). CONCLUSIONS: In U.S. practice, the utilization of EM steadily increased in low-risk PCa and remained low in the intermediate-risk group over time. While patients with advanced age or comorbidities were more likely to receive EM, its use varied substantially by geographic region. Our findings bring attention to the presence of multiple barriers for EM implementation.

Initiation of Trastuzumab by Women Younger Than 64 Years for Adjuvant Treatment of Stage I-III Breast Cancer.

Purpose: Studies have reported disparities by age and race in the initiation of adjuvant trastuzumab for the initial treatment of older women with early-stage breast cancer, but less is known about its initiation in younger patients. Therefore, we assessed temporal trends and clinical and demographic factors associated with trastuzumab initiation in a large, population-based cohort of patients aged <64 years in 5 states. Methods: Using a cancer registry and claims-linked data set of 13,398 women with incident invasive breast cancer from 2006 to 2011, we identified 934 patients aged <64 years with HER2-positive stage I-III breast cancer. We assessed trastuzumab initiation within the first 9 months after diagnosis and conducted logistic regression analyses to assess sociodemographic and clinical factors associated with trastuzumab initiation. Results: From 2006 to 2011, trastuzumab initiation steadily increased in patients with node-positive (from 65% to 91%) and node-negative (from 39% to 75%) breast cancers. Several tumor-related factors were associated with trastuzumab initiation, including high histologic grades (adjusted odds ratio [aOR], 6.43; 95% CI, 3.27-12.65; and aOR, 3.25; 95% CI, 1.66-6.36, for grades 3 and 2, respectively), node-positive status (aOR, 1.88; 95% CI, 1.28-2.78; P=.001), tumor size >2 cm (aOR, 1.50; 95% CI, 1.04-2.16; P=.03), and hormone receptor-negative status (aOR, 1.51; 95% CI, 1.01-2.26; P=.04). We found a null effect of race. Conclusions: Adjuvant trastuzumab therapy for early-stage breast cancer has been widely disseminated among women aged <64 years. The initiation of this targeted therapy was associated with higher-risk features, consistent with practice guidelines.

Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study.

PURPOSE: Randomized trials have shown that intermittent androgen deprivation therapy for patients with advanced prostate cancer may improve sexual and physical functioning compared to continuous androgen deprivation therapy without compromising survival. To our knowledge it is unknown whether intermittent androgen deprivation therapy alters the risk of serious toxicities associated with continuous androgen deprivation therapy. MATERIALS AND METHODS: We performed a population based cohort study of 9,772 men 66 years old or older who were diagnosed with advanced prostate cancer from 2002 to 2011 and treated with androgen deprivation therapy. Intermittent androgen deprivation therapy was defined as a single 90-day interval between 2 androgen deprivation therapy sessions during which patients visited their physicians or underwent prostate specific antigen testing. Outcomes included acute myocardial infarction, stroke, heart failure, type 2 diabetes and fracture. We used Cox proportional hazard models to estimate the HRs of the comparative risk of serious toxicities between intermittent and continuous androgen deprivation therapy. RESULTS: A total of 2,113 (22%), 769 (9%) and 899 men (9%) had a new cardiovascular event, diabetes or fracture, respectively, within 5 years of starting androgen deprivation therapy. Compared to the continuous androgen deprivation therapy group, the intermittent therapy group was at lower risk for serious cardiovascular events (HR 0.64, 95% CI 0.53-0.77), particularly in reducing the risk of heart failure (HR 0.62, 95% CI 0.49-0.78) and fracture (HR 0.52, 95% CI 0.38-0.70, each p <0.0001). CONCLUSIONS: Intermittent androgen deprivation therapy was associated with a lower risk of heart failure and fracture compared to continuous androgen deprivation therapy. This raises toxicity concerns for continuous relative to intermittent therapy and suggests that intermittent androgen deprivation therapy may represent a safer therapeutic choice in elderly men with advanced prostate cancer.

Mortality and Androgen Deprivation Therapy as Salvage Treatment for Biochemical Recurrence after Primary Therapy for Clinically Localized Prostate Cancer.

PURPOSE: Androgen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study. MATERIALS AND METHODS: From 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor. RESULTS: Overall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70-1.35 or HR 1.18, 95% CI 0.68-2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70-1.01 or HR 1.06, 95% CI 0.80-1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20-0.63 and HR 0.43, 95% CI 0.21-0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48-0.80 and HR 0.65, 95% CI 0.47-0.90, respectively). CONCLUSIONS: We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy.

Efficient Estimation of the Cox Model With Auxiliary Subgroup Survival Information.

With the rapidly increasing availability of data in the public domain, combining information from different sources to infer about associations or differences of interest has become an emerging challenge to researchers. This paper presents a novel approach to improve efficiency in estimating the survival time distribution by synthesizing information from the individual-level data with t-year survival probabilities from external sources such as disease registries. While disease registries provide accurate and reliable overall survival statistics for the disease population, critical pieces of information that influence both choice of treatment and clinical outcomes usually are not available in the registry database. To combine with the published information, we propose to summarize the external survival information via a system of nonlinear population moments and estimate the survival time model using empirical likelihood methods. The proposed approach is more flexible than the conventional meta-analysis in the sense that it can automatically combine survival information for different subgroups and the information may be derived from different studies. Moreover, an extended estimator that allows for a different baseline risk in the aggregate data is also studied. Empirical likelihood ratio tests are proposed to examine whether the auxiliary survival information is consistent with the individual-level data. Simulation studies show that the proposed estimators yield a substantial gain in efficiency over the conventional partial likelihood approach. Two sets of data analysis are conducted to illustrate the methods and theory.

Use of androgen deprivation therapy as salvage treatment after primary therapy for clinically localized prostate cancer.

PURPOSE: The optimal use of androgen deprivation therapy as salvage treatment (sADT) for men after initial prostatectomy or radiotherapy for clinically localized prostate cancer is undefined. We describe patterns of sADT use and investigate clinical and sociodemographic characteristics of insured men who received sADT versus surveillance in managed care settings. METHODS: Using comprehensive electronic health records and cancer registry data from three integrated health plans, we identified all men with newly diagnosed clinically localized prostate cancer between 1995 and 2009 who received either prostatectomy (n = 16,445) or radiotherapy (n = 19,531) as their primary therapy. We defined sADT based on the timing of ADT following primary therapy and stage of cancer. We fit Cox proportional hazard models to identify sociodemographic characteristics and clinical factors associated with sADT. RESULTS: With a median follow-up of 6 years (range 2-15 years), 13 % of men who underwent primary prostatectomy or radiotherapy received sADT. After adjusting for selected covariates, sADT was more likely to be used in men who were older (e.g., HR 1.70, 95 % CI 1.48-1.96 or HR 1.33, 95 % CI 1.17-1.52 for age 70+ relative to age 35-59 for primary prostatectomy or radiotherapy, respectively), were African-American, had a short PSA doubling time, had a higher pre-treatment risk of progression, had more comorbidities, and received adjuvant ADT for initial disease. CONCLUSIONS: In men with localized prostate cancer in community practice initially treated with prostatectomy or radiotherapy, sADT after primary treatment was more frequent for men at greater risk of death from prostate cancer, consistent with practice guidelines.

Cardiovascular toxicity after antiangiogenic therapy in persons older than 65 years with advanced renal cell carcinoma.

BACKGROUND: Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population-based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, this study analyzed patients who were 66 years old or older and were diagnosed with RCC from 2000 to 2009. The incidence of cardiovascular adverse events, including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths, was examined through December 2010. A Cox proportional hazards model was created to calculate the hazard ratio (HR), and adjustments were made for age, sex, comorbidity, and the use of other systemic therapy. RESULTS: A total of 171 of 670 patients who received sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of cardiovascular events (HR, 1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84; 95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC from 2007 to 2009 who were eligible for Part D but did not receive either agent. In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the highest increased risk of stroke associated with the use of either or both drugs. CONCLUSIONS: Sunitinib and sorafenib might be associated with an increased risk of cardiovascular events and particularly stroke.

Adoption of Gene Expression Profiling for Breast Cancer in US Oncology Practice for Women Younger Than 65 Years.

BACKGROUND: A number of practice guidelines incorporate the use of gene expression profiling (GEP) tests for early-stage, hormone receptor-positive, HER2-negative breast tumors. Few studies describe factors associated with GEP testing in US oncology practice. We assessed the relationship between clinical, demographic, and group-level socioeconomic variables and test use in women younger than 65 years. PATIENTS AND METHODS: Data from 5 state cancer registries were linked with insurance claims data and GEP test results. We assessed rates of testing and variables associated with test use in an incident cohort of 9,444 commercially insured women younger than 65 years, newly diagnosed with stage I or II hormone receptor-positive breast cancer from 2006 through 2012. RESULTS: Rates of testing for women with N0 disease increased from 20.4% in 2006 to 35.2% in 2011. Variables associated with higher rates of testing, beyond clinical factors such as nodal status (P<.001), included being diagnosed from 2008 through 2012 versus 2006 through 2007 (adjusted odds ratio [OR], 1.67; 95% CI, 1.47-1.90), having preexisting comorbidities (adjusted OR, 1.35; 95% CI, 1.14-1.59), and higher out-of-pocket pharmacy costs (adjusted OR, 1.66; 95% CI, 1.40-1.97). Women younger than 50 years were more likely to be tested if they had stage I versus stage II disease (P<.0001). CONCLUSIONS: In an insured population of women younger than 65 years, GEP testing increased after its inclusion in clinical practice guidelines and mounting evidence. Additional research is needed to better understand oncologists' decision not to order GEP testing for their patients who are otherwise eligible.

Population-based study of the effect of gene expression profiling on adjuvant chemotherapy use in breast cancer patients under the age of 65 years.

BACKGROUND: Gene expression profiling (GEP) testing can help to predict the risk of cancer recurrence and guide decisions about adjuvant chemotherapy for breast cancer (BC). However, no prior US studies have evaluated the relation between GEP testing and the use of adjuvant chemotherapy by women treated in a general oncology practice. METHODS: Eligible patients were women under the age 65 of years who were newly diagnosed with their first stage I or II, hormone receptor-positive BC between 2006 and 2011 (n = 9405). This retrospective study was conducted with a data set consisting of registry data, health claims data, and GEP testing results. The distribution of GEP test results was reported in terms of the risk of recurrence predicted, and logistic regression was used to assess the association of test results with chemotherapy use, with adjustments made for multiple patient characteristics. RESULTS: The proportions of tested women with low, intermediate, and high recurrence score results were 51%, 39%, and 10%, respectively. Among these women, 11%, 47%, and 88%, respectively, received adjuvant chemotherapy. There was a significant, positive linear relation of assay scores with chemotherapy use within the low and intermediate subgroups after adjustments for all other factors (adjusted odds ratios, 1.17 and 1.20, respectively). CONCLUSIONS: Adjuvant chemotherapy use after GEP testing is generally consistent with the recommended test interpretation for women with a high or low predicted risk of recurrence. Chemotherapy use in the intermediate-risk group increased with Recurrence Score values, and evidence from ongoing randomized trials may help to clarify whether this finding reflects optimal interpretation of GEP test results. These results demonstrate the principle that genomic testing, on the basis of research establishing its utility, can be applied appropriately in general practice in accordance with guideline recommendations.

Radiation therapy at the end of life: a population-based study examining palliative treatment intensity.

BACKGROUND: To examine factors associated with the use of radiation therapy (RT) at the end of life in patients with breast, prostate, or colorectal cancer. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) - Medicare database, patients were over age 65 and diagnosed between January 1, 2004 and December 31, 2011 with any stage of cancer when the cause of death, as defined by SEER, was cancer; or with stage 4 cancer, who died of any cause. We employed multiple logistic regression models to identify patient and health systems factors associated with palliative radiation use. RESULTS: 50% of patients received RT in the last 6 months of life. RT was used less frequently in older patients and in non-Hispanic white patients. Similar patterns were observed in the last 14 days of life. Chemotherapy use in the last 6 months of life was strongly correlated with receiving RT in the last 6 months (OR 2.72, 95% CI: 2.59-2.88) and last 14 days of life (OR 1.55, 95% CI: 1.40-1.66). Patients receiving RT accrued more emergency department visits, radiographic exams and physician visits (all comparisons p < 0.0001). CONCLUSIONS: Among patients with breast, colorectal, and prostate cancer, palliative RT use was common. End-of-life RT correlated with end-of-life chemotherapy use, including in the last 14 days of life, when treatment may cause increased treatment burden without improved quality of life. Research is needed optimize the role and timing of RT in palliative care.

Adoption of Intermittent Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study in American Urology Practice.

INTRODUCTION: In several developed countries intermittent androgen deprivation therapy has been accepted over continuous androgen deprivation therapy for advanced prostate cancer management. To our knowledge its adoption and predictors of use in American urology practice remain unknown. METHODS: Using SEER-Medicare data we identified a cohort of men 66 years old or older who were newly diagnosed with prostate cancer with metastasis or with treated recurrence in whom androgen deprivation therapy was started during 2003 to 2007. We determined intermittent androgen deprivation therapy receipt based on interruptions longer than 3 months between scheduled and actual therapy injections, and physician visits and prostate specific antigen tests during the interruption. Predictors included patient and physician characteristics. We performed logistic regression analysis separately in the metastatic and treated recurrence groups using generalized estimating equations to account for the clustering effect of patients treated by the same physician. RESULTS: Our cohort included 4,281 men, of whom 2,487 with metastasis and 1,794 with treated recurrence received intermittent androgen deprivation therapy. In patients who received intermittent rather than continuous therapy the median duration of therapy was by 6.4 and 9.0 months longer in those with metastasis and treated recurrence, respectively. Each patient group showed significant variation in intermittent therapy use by region (p <0.0001). There was lower intermittent androgen deprivation therapy use in the Eastern and Central regions than in the Mountain and Pacific regions. CONCLUSIONS: Intermittent androgen deprivation therapy has not been widely used in American urology practice. Its adoption shows substantial variation by geographic regions. These regional differences likely reflect uncertainty regarding the efficacy of this therapy among providers as well as differences in patient preferences and involvement in treatment decision making.

Risk of diabetes among patients receiving primary androgen deprivation therapy for clinically localized prostate cancer.

PURPOSE: Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. MATERIALS AND METHODS: We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. RESULTS: Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008). CONCLUSIONS: Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.

The effects of cardiovascular disease on the clinical outcome of elderly patients with diffuse large B-cell lymphoma.

We identified 3910 elderly (>65 yrs) patients with diffuse large B-cell lymphoma (DLBCL) who received doxorubicin-based (+/-rituximab) therapy and 77 347 cancer-free controls, and assessed cardiovascular events and survival in relation to preexisting cardiovascular comorbidities. Compared to controls, patients with DLBCL had a 3.4-fold (95%CI 3.0-3.9) and 2.5-fold (95%CI 2.3-2.7) increased risk of congestive heart failure (CHF)/cardiomyopathy (CM) within 6 months and 3 years of diagnosis, respectively. Risk of acute myocardial infarction (AMI) was similarly increased. The risk of CHF/CM and AMI was significantly higher in those patients with DLBCL (vs. controls) who did not report preexisting cardiovascular disease, compared to those who had preexisting cardiovascular disease; this was due to dose reductions of doxorubicin among patients with preexisting cardiovascular disease. Rituximab improved survival in patients with stage III-IV (but not I-II) disease (p-interaction = 0.0003). Our novel findings emphasize the need to reduce cardiac toxicity of doxorubicin in elderly DLBCL patients.

Effectiveness of primary androgen-deprivation therapy for clinically localized prostate cancer.

PURPOSE: Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. METHODS: We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. RESULTS: Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). CONCLUSION: We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.

Utilization of bevacizumab in US elderly patients with colorectal cancer receiving chemotherapy.

OBJECTIVE: Bevacizumab, the first FDA-approved anti-angiogenesis agent, has been used for metastatic colorectal cancer since 2004. This study evaluated the utilization of bevacizumab among elderly metastatic colorectal cancer patients in the United States. METHODS: Using Surveillance and Epidemiology and End Results (SEER)-Medicare data, this retrospective cohort study consisted of individuals aged 65 years or older with a colorectal cancer diagnosis between 2005 and 2009, who received chemotherapy any time through 2010. This included patients with newly diagnosed metastatic colorectal cancer and patients who progressed from initially diagnosed earlier-stage disease. We ascertained comorbid conditions using ICD-9 codes and conducted logistic regression to identify patients' characteristics associated with bevacizumab use. RESULTS: A total of 8645 patients were identified (mean age 74 years; 52% male); 57% of patients received bevacizumab with initially diagnosed metastatic colorectal cancer and 44% of patients with treated progressive or recurrent disease. After adjusting for other covariates, we found that patients aged ≥80 years were less likely to receive bevacizumab compared with those aged 65-69 years (odds ratio (OR), 0.64 (95% confidence interval (CI): 0.57-0.73)), or if they had evidence of comorbid cardiomyopathy/congestive heart failure (OR, 0.82 (CI: 0.70-0.95)) or arrhythmic disorder (OR, 0.85 (CI: 0.75-0.96)). Adoption of bevacizumab into practice was rapid following its approval, and the use increased from 36% to 40% from 2005 to 2010 (p = 0.013). There were significant regional variations in bevacizumab use. CONCLUSIONS: Despite rapid uptake since its original approval, there appears to be low use of bevacizumab in elderly metastatic colorectal cancer patients in the United States. Regional variations and the strong effects of age and comorbidity suggest lack of consensus among oncologists regarding benefits and risks of bevacizumab in elderly patients.