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 Risk of Methylphenidate Pharmacotherapy for Adults with ADHD

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. It was once thought to be a disorder affecting only children, but in those undiagnosed in childhood, symptoms do not disappear with age. There is now a growing recognition of the late diagnosis and treatment of adults with ADHD. The first-line drug in pharmacotherapy is methylphenidate, and information about its adverse effects, when used by adults, has not been as extensively described as in children. The aim of this article was to review the literature describing the risks of methylphenidate therapy for adults with ADHD. A total of 19 articles—15 clinical trials and 4 case reports presenting rare side effects resulting from methylphenidate therapy, such as reversible ischemic stroke, myocardial infarction, and psychotic episodes, were analyzed. The analysis from clinical trials included 3458 adult patients with ADHD and described the most common side effects, psychiatric adverse events, effects of methylphenidate treatment on sleep, laboratory results, body mass, and cardiovascular symptoms. Methylphenidate treatment is well tolerated, with side effects described, according to severity, as mild to moderate. We conclude that pharmacotherapy is not risk-free and methylphenidate, due to its side effects, may not be the first drug of choice for every patient

Biopsychosocial Variables in Male Schizophrenic Patients: A Comprehensive Comparison with Healthy Controls

Objective: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). Methods: participants underwent a battery of neuropsychological tests including the Trail Making Test (TMT), Stroop Color-Word Interference Test, and Verbal Fluency Test. Psychopathological symptoms in the SZ group were evaluated using the Positive and Negative Syndrome Scale (PANSS). Anthropometric measurements such as body weight, height, BMI, and waist circumference were taken. Biochemical markers measured included fasting glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and fasting insulin. Lifestyle factors were assessed through a questionnaire for the study of views and eating habits of people aged 16 to 65. Results: the HC group outperformed the SZ group in the TMT_A test and the Stroop test, but no significant differences were observed in the TMT_B test or in phonemic fluency tests. No correlation was found between age and PANSS scores within the SZ group. Anthropometrically, the SZ group had higher body weight, waist circumference, and BMI, with no difference in height. Biochemically, the HC group had higher HDL cholesterol levels but lower insulin and insulin resistance indices. Pharmacological assessment showed a more significant impact on body weight among SZ patients taking second-generation antipsychotics. Lifestyle factors such as diet and screen time were comparable between groups, but the SZ group reported longer sleep duration and lower leisure time activity. Conclusions: our study highlights distinct neuropsychological, pharmacological, anthropometric, and biochemical differences between male schizophrenic patients and healthy controls. The results underscore the complexity of schizophrenia and point toward the need for a multi-faceted approach to its management and understanding