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

State and Local Tobacco Control Policies Are Associated With Decreasing Cigarette Smoking Rates and Disparities

Summary: While California as a whole has made significant progress over the past three decades in reducing rates of cigarette smoking, progress across communities in the state has been uneven.1 Using the 2014–2019 California Health Interview Survey (CHIS) combined adult data and existing state, county, and city tobacco control policies and neighborhood-level data on social drivers of health, this brief examines variations in local tobacco policies and their relationship with smoking behaviors, particularly among priority populations disproportionately impacted by tobacco. Findings: In 2019, more than 60% of California cities still had weak or no local tobacco policies. Inequities in protection by tobacco control policies persist across priority populations, especially in areas with low neighborhood socioeconomic status (NSES). Reductions in adult cigarette smoking were greater in cities with strong local tobacco policies than in those with weak or no policies. Strong local policies were also associated with decreased smoking rates among adult (18+) populations disproportionately impacted by the tobacco epidemic, thereby reducing social inequalities in cigarette smoking. This study also found that the positive effect of local tobacco control policies on current adult smoking rates was further enhanced when the state-level tobacco policy (i.e., raising the tax from $0.87 to$2.87 per pack) was enacted in April 2017

Multisectoral Collaborations to Increase the Use of Recommended Cancer Screening and Other Clinical Preventive Services by Older Adults

The Healthy Aging Partnerships in Prevention Initiative (HAPPI) is a multisectoral collaboration that aims to increase use of recommended cancer screening and other clinical preventive services (CPS) among underserved African American and Latino adults aged 50 and older in South Los Angeles. HAPPI uses the principles of the evidence-based model Sickness Prevention Achieved through Regional Collaboration to increase capacity for the delivery of breast, cervical, and colorectal cancer screening, as well as influenza and pneumococcal immunizations, and cholesterol screening. This article describes HAPPI's collaborative efforts to enhance local capacity by training personnel from community health centers (CHCs) and community-based organizations (CBOs), implementing a small grants program, and forming a community advisory council. HAPPI demonstrates that existing resources in the region can be successfully linked and leveraged to increase awareness and receipt of CPS. Five CHCs expanded quality improvement efforts and eight CBOs reached 2,730 older African Americans and Latinos through locally tailored educational programs that encouraged community-clinic linkages. A community council assumed leadership roles to ensure HAPPI sustainability. The lessons learned from these collective efforts hold promise for increasing awareness and fostering the use of CPS by older adults in underserved communities

Unequal Protection: Secondhand Smoke Threatens Health of Tenants in Multi-Unit Housing in Los Angeles.

Secondhand smoke is dangerous to a person's health at any level of exposure. Yet policies that prevent smoking are not in place for a majority of market-rate multi-unit housing complexes, according to a new survey of nearly 1,000 apartment dwellers in the city of Los Angeles. Approximately 37 percent of respondents reported that secondhand smoke had drifted into their apartments in the past year. Households with members of vulnerable populations, such as children or individuals with chronic conditions, are more likely to report smoke drifting from adjacent units. Four out of five respondents--including more than half of those who self-reported currently smoking--supported a smoke-free policy in common areas and/or individual units

Unequal Protection: Secondhand Smoke Threatens Health of Tenants in Multi-Unit Housing in Los Angeles.

Secondhand smoke is dangerous to a person's health at any level of exposure. Yet policies that prevent smoking are not in place for a majority of market-rate multi-unit housing complexes, according to a new survey of nearly 1,000 apartment dwellers in the city of Los Angeles. Approximately 37 percent of respondents reported that secondhand smoke had drifted into their apartments in the past year. Households with members of vulnerable populations, such as children or individuals with chronic conditions, are more likely to report smoke drifting from adjacent units. Four out of five respondents--including more than half of those who self-reported currently smoking--supported a smoke-free policy in common areas and/or individual units

Highlights from an Expert Meeting on Opportunities for Cancer Prevention among Older Adults

© 2019 Published by Oxford University Press on behalf of The Gerontological Society of America 2019. This paper provides highlights from an expert meeting to explore opportunities to reduce cancer risk and promote health at older ages. Factors that increase cancer risk among older adults include exposure to carcinogens from multiple sources, chronic conditions such as obesity and diabetes, and unhealthy behaviors. Emerging research points to chronic social stressors - social isolation, loneliness, and financial hardship - as being linked to accelerated biological aging and increased cancer risk later in life. Older adults may disproportionately encounter these stressors as well as barriers to preventive health care services, accurate health information, and environments that promote health. Researchers can use existing cohort studies of older adults to deepen our understanding of the relative benefit of modifying specific behaviors and circumstances. The evidence points to the value of comprehensive, transdisciplinary approaches to promote health and reduce cancer risk across the entire lifespan, extending through older adulthood. Clinical encounters with older adults provide opportunities for psychosocial and behavioral screening and counseling. In the presence of multiple morbidities, preventive health services may offer greater health benefits than cancer-screening tests. Strategies that involve families and caregivers, promote positive attitudes about aging, and engage many different community sectors have the potential to prevent or delay the development of cancer at older ages

Highlights From an Expert Meeting on Opportunities for Cancer Prevention Among Older Adults.

This paper provides highlights from an expert meeting to explore opportunities to reduce cancer risk and promote health at older ages. Factors that increase cancer risk among older adults include exposure to carcinogens from multiple sources, chronic conditions such as obesity and diabetes, and unhealthy behaviors. Emerging research points to chronic social stressors - social isolation, loneliness, and financial hardship - as being linked to accelerated biological aging and increased cancer risk later in life. Older adults may disproportionately encounter these stressors as well as barriers to preventive health care services, accurate health information, and environments that promote health. Researchers can use existing cohort studies of older adults to deepen our understanding of the relative benefit of modifying specific behaviors and circumstances. The evidence points to the value of comprehensive, transdisciplinary approaches to promote health and reduce cancer risk across the entire lifespan, extending through older adulthood. Clinical encounters with older adults provide opportunities for psychosocial and behavioral screening and counseling. In the presence of multiple morbidities, preventive health services may offer greater health benefits than cancer-screening tests. Strategies that involve families and caregivers, promote positive attitudes about aging, and engage many different community sectors have the potential to prevent or delay the development of cancer at older ages