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

The impact of a family-based assessment and intervention healthy lifestyle programme on health knowledge and beliefs of children with obesity and their families

Objective: To determine the impact of a family-based assessment-and-intervention healthy lifestyle programme on health knowledge and beliefs of children and families affected by obesity. Second, to compare the health knowledge of the programme cohort to those of a national cohort in Aotearoa/New Zealand (NZ). Design: This mixed-methods study collected health knowledge and health belief data in a questionnaire at baseline and 12-, 24-, and 60-month follow-up assessments. Health knowledge over time was compared with baseline knowledge and with data from a nationally representative survey. A data-driven subsumption approach was used to analyse open-text responses to health belief questions across the study period. Setting: Taranaki region, a mixed urban–rural setting in NZ. Participants: Participants (caregiver/child dyads) from the Whānau Pakari randomised trial. Results: A greater proportion of the cohort correctly categorised foods and drinks as healthy or unhealthy at 12 months compared to baseline for most questionnaire items. Retention of this health knowledge was evident at 24- and 60-month follow-ups. More than twice as many participants correctly reported physical activity recommendations at follow-up compared to baseline (p < 0.001). Health knowledge of participants was similar to the national survey cohort at baseline, but surpassed it at 12 and 24 months. Participant beliefs around healthy lifestyles related to physical functioning, mental and emotional wellbeing, and enhancement of appearance, and gained greater depth and detail over time. Conclusions: This study demonstrates the important role that community-level healthy lifestyle programmes can have in knowledge-sharing and health promotion

Participants’ and caregivers’ experiences of a multidisciplinary programme for healthy lifestyle change in Aotearoa/New Zealand: a qualitative, focus group study

Objective Child and adolescent obesity continues to be a major health issue internationally. This study aims to understand the views and experiences of caregivers and participants in a child and adolescent multidisciplinary programme for healthy lifestyle change.Design Qualitative focus group study.Setting Community-based healthy lifestyle intervention programme in a mixed urban–rural region of Aotearoa/New Zealand.Participants Parents/caregivers (n=6) and children/adolescents (n=8) who participated in at least 6 months of an assessment and weekly session, family-based community intervention programme for children and adolescents affected by obesity.Results Findings covered participant experiences, healthy lifestyle changes due to participating in the programme, the delivery team, barriers to engagement and improvements. Across these domains, four key themes emerged from the focus groups for participants and their caregivers relating to their experience: knowledge-sharing, enabling a family to become self-determining in their process to achieve healthy lifestyle change; the importance of connectedness and a family-based programme; the sense of a collective journey and the importance of a nonjudgemental, respectful welcoming environment. Logistical challenges and recommendations for improvement were also identified.Conclusions Policymakers need to consider the experiences of participants alongside quantitative outcomes when informing multidisciplinary intervention programmes for children and adolescents affected by obesity.Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR):12611000862943; Post-results