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

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study

Objectives:. To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. Design:. A multicenter, prospective, observational study was performed between August 2018 and January 2019. Setting:. Community and academic hospitals in the United States. Participants:. Emergency medicine clinical pharmacists. Interventions:. Recommendations classified into one of 38 intervention categories associated with cost avoidance. Measurements and Main Results:. Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions;$2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122;$1,787,170), prophylaxis (24; $22,804), hands-on care (3,533;$2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was$538.61 per intervention, $875.60 per patient, and$8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between$1.4:1 and $10.6:1. Conclusions:. Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between$1.4:1 and $10.6:1