Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Race, socioeconomic status, and premature mortality.

This article summarizes the results of a study examining whether the relationship between race and premature mortality varied by socioeconomic status among men and women who are black or white and between the ages of 25 and 64 years. Using a population-based study design, we tested the hypothesis that the association between race and mortality would differ by socioeconomic status as measured by neighborhood poverty and educational status. We found that the odds of dying prematurely were greater for black men and women who lived in less-affluent neighborhoods than for white men and women who lived in similar neighborhoods. Racial differences were most striking, however, for both black women and white women who lived in more affluent neighborhoods. Our results suggest that socioeconomic status does moderate the effects of race on premature mortality. Strategies to reduce racial disparities in premature mortality in Minnesota must include developing more coordinated health, social, and economic policies and delivering health messages that resonate with younger, more affluent African-American women

The 2008-2009 recession and alcohol outcomes: differential exposure and vulnerability for Black and Latino populations.

ObjectiveWe examined whether race/ethnicity was related to exposure to acute economic losses in the 2008-2009 recession, even accounting for individual-level and geographic variables, and whether it influenced associations between economic losses and drinking patterns and problems.MethodData were from the 2010 National Alcohol Survey (N = 5,382). Surveys assessed both severe losses (i.e., job and housing loss) and moderate losses (i.e., reduced hours/pay and trouble paying the rent/mortgage) attributed to the 2008-2009 recession. Alcohol outcomes included total annual volume, monthly drunkenness, drinking consequences, and alcohol dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition).ResultsCompared with Whites, Blacks reported significantly greater exposure to job loss and trouble paying the rent/mortgage, and Latinos reported greater exposure to all economic losses. However, only Black-White differences were robust in multivariate analyses. Interaction tests suggested that associations between exposure to economic loss and alcohol problems were stronger among Blacks than Whites. Given severe (vs. no) loss, Blacks had about 13 times the odds of both two or more drinking consequences and alcohol dependence, whereas the corresponding odds ratios for Whites were less than 3. Conversely, associations between economic loss and alcohol outcomes were weak and ambiguous among Latinos.ConclusionsResults suggest greater exposure to economic loss for both Blacks and Latinos (vs. Whites) and that the Black population may be particularly vulnerable to the negative effects of economic hardship on the development and/or maintenance of alcohol problems. Findings extend the economic literature and signal policy makers and service providers that Blacks and Latinos may be at special risk during economic downturns

Does Socioeconomic Position Moderate the Effects of Race on Cardiovascular Disease Mortality?

Objective: Cardiovascular disease (CVD) rates differ markedly by minority status, with younger Blacks having some of the highest CVD mortality rates in the United States. A major objective of this study was to assess whether socioeconomic position moderates the effects of race or minority status on CVD mortality. Design: The sample included 443 Black and 21,182 White men, and 415 Black and 24,929 White women, 45 years and older, who died of CVD from 1992±1998, and who had lived in the Twin Cities 5-county area. Using individual and neighborhood level measures of socioeconomic position, we hypothesized that socioeconomic position would moderate the effects of race on CVD mortality. Test hypotheses were analyzed using Poisson regression analysis. Results: Socioeconomic position moderated the effects of race on CVD mortality among older men, but not in older women. Older Black men who lived in more impoverished neighborhoods had signi®cantly and disproportionately higher CVD mortality rates than did older White men living in more impoverished neighborhoods; this was not the case among older Black and White men living in less impoverished neighborhoods. Race was independently related to CVD mortality among younger men and women, with younger Black men and women having significantly higher CVD mortality rates than younger White men and women. The Black-White rate for Black women was twice that of White women. Conclusion: Socioeconomic position as measured by neighborhood poverty can moderate the effects of race on CVD mortality in older Black and White men. This may not have been as apparent had socioeconomic position not been treated as a major variable of interest, and measured at multiple levels

Does socioeconomic position moderate the effects of race of cardiovascular disease mortality?

Objective: Cardiovascular disease (CVD) rates differ markedly by minority status, with younger Blacks having some of the highest CVD mortality rates in the United States. A major objective of this study was to assess whether socioeconomic position moderates the effects of race or minority status on CVD mortality. Design: The sample included 443 Black and 21,182 White men, and 415 Black and 24,929 White women, 45 years and older, who died of CVD from 1992-1998, and who had lived in the Twin Cities 5-county area. Using individual and neighborhood level measures of socioeconomic position, we hypothesized that socioeconomic position would moderate the effects of race on CVD mortality. Test hypotheses were analyzed using Poisson regression analysis. Results: Socioeconomic position moderated the effects of race on CVD mortality among older men, but not in older women. Older Black men who lived in more impoverished neighborhoods had significantly and disproportionately higher CVD mortality rates than did older White men living in more impoverished neighborhoods; this was not the case among older Black and White men living in less impoverished neighborhoods. Race was independently related to CVD mortality among younger men and women, with younger Black men and women having significantly higher CVD mortality rates than younger White men and women. The Black-White rate for Black women was twice that of White women. Conclusion: Socioeconomic position as measured by neighborhood poverty can moderate the effects of race on CVD mortality in older Black and White men. This may not have been as apparent had socioeconomic position not been treated as a major variable of interest, and measured at multiple levels

Competency-Based Faculty Development in Community-Engaged Scholarship: A Diffusion of Innovation Approach

Abstract The authors utilized interviews, competency surveys, and document review to evaluate the effectiveness of a one-year, cohort-based faculty development pilot program, grounded in diffusion of innovations theory, and aimed at increasing competencies in community engagement and community-engaged scholarship. Five innovator participants designed the program for five early adopter participants. The program comprised training sessions and individual mentoring. Training sessions focused on the history and concepts of community-engaged scholarship; competencies in engaged research and teaching; and navigation of career advancement as a community-engaged scholar. Mentoring focused on individual needs or disciplinespecific issues. The interviews and surveys indicated that the participants gained knowledge in specific areas of communityengaged scholarship. Critical program features and lessons learned are explored

Patterns of alcohol policy enforcement activities among local law enforcement agencies: A latent class analysis

AIMS: We assessed levels and patterns of alcohol policy enforcement activities among U.S. local law enforcement agencies. DESIGN/SETTING/PARTICIPANTS: We conducted a cross-sectional survey of a representative sample of 1,631 local law enforcement agencies across the 50 states. MEASURES/METHODS: We assessed 29 alcohol policy enforcement activities within each of five enforcement domains—underage alcohol possession/consumption, underage alcohol provision, underage alcohol sales, impaired driving, and overservice of alcohol—and conducted a series of latent class analyses to identify unique classes or patterns of enforcement activity for each domain. FINDINGS: We identified three to four unique enforcement activity classes for each of the enforcement domains. In four of the domains, we identified a Uniformly Low class (i.e., little or no enforcement) and a Uniformly High enforcement activity class (i.e., relatively high levels of enforcement), with one or two middle classes where some but not all activities were conducted. The underage provision domain had a Uniformly Low class but not a Uniformly High class. The Uniformly Low class was the most prevalent class in three domains: underage provision (58%), underage sales (61%), and overservice (79%). In contrast, less than a quarter of agencies were in Uniformly High classes. CONCLUSIONS: We identified qualitatively distinct patterns of enforcement activity, with a large proportion of agencies in classes characterized by little or no enforcement and fewer agencies in high enforcement classes. An important next step is to determine if these patterns are associated with rates of alcohol use and alcohol-related injury and mortality