PurposeThere are known associations between treatment of prostate cancer (PCa) involving Androgen Deprivation Therapy (ADT) and psychological and physical side effects. We investigate the associations between cancer-related symptoms, health-related quality of life (HRQL), and poor psychological outcomes in men whose treatment for PCa involved ADT.MethodsA cross-sectional postal questionnaire was administered to UK men 18–42 months post diagnosis of PCa. Men completed items on functional outcomes using the Expanded Prostate Cancer Index Composite (EPIC-26), EuroQol-5D (EQ-5D), and the European Organisation for Research and Treatment of Cancer (EORTC) Fatigue subscale. Psychological outcomes (mental well-being and psychological distress) were assessed using the Short Warwick–Edinburgh Mental Well-being Scale (SWEMWBS) and the Kessler 6-item scale (K6), respectively. Associations between explanatory variables and psychological outcomes were assessed using stepped logistic regression.Results13,097 men treated with ADT completed a questionnaire. A minority of men reported poor mental well-being (15.5%) or severe psychological distress (6.6%). After controlling for sociodemographic and clinical variables, reporting clinically significant fatigue was strongly associated with severe psychological distress (OR 9.92; 95% CI 7.63 to 12.89) and poor well-being (OR 3.86; 95% CI 3.38 to 4.42). All cancer-related symptoms and HRQL variables were associated with both psychological outcomes.ConclusionsWhile the majority of men treated with ADT did not report poor psychological outcomes, a small proportion reported severe problems. Clinically significant fatigue was demonstrated as a possible indicator of poor outcomes. Healthcare systems need to have clear protocols in place which specifically and routinely target psychological distress and fatigue.