Background: Due to side effects of invasive treatments, prostate cancer (PC) patients face long-term quality of life (QoL) concerns and enduring psychosocial distress. We explored how QoL is linked to distress among a national sample of men with PC. Methods: 214 men with PC enrolled in the Cancer Support Community’s Cancer Experience Registry. Participants provided demographic/clinical background and completed the Prostate Cancer-Related QoL Scales, covering 6 QoL domains (urinary control, sexual intimacy, sexual confidence, masculine self-esteem, cancer control, and treatment regret). Psychosocial distress was captured by CancerSupportSource, a 25-item tool with 2-item depression and anxiety screening subscales. Scores ≥3 indicate risk for clinically significant depression or anxiety respectively, and signal need for referral and further assessment. We examined bivariate correlations between demographic/clinical background, QoL, and prevalence of ‘risk for clinically significant anxiety and depression’, and used logistic regression to calculate odds of anxiety and depression risk by QoL, adjusting for demographic/clinical variables. Results: Participants were 93% White; mean (SD) age=64 (12) years; mean (SD) years since diagnosis=4.3 (4.9); 25% had metastatic disease. 54% underwent radiation; 55% surgery. 40% were at risk for clinically significant anxiety; 35% depression. Poorer QoL scores for sexual intimacy, sexual confidence, masculine self-esteem, cancer control, and treatment regret were bivariately associated with anxiety (p<.05) and depression (p<.001) risk. In logistic regression, poorer perceived cancer control predicted anxiety risk (R²=.44; OR=0.97; p<.01). Lower masculine self-esteem predicted depression risk (R²=.68; OR=0.88; p<.05). Conclusions: Questioning treatment efficacy and worrying about disease progression (i.e., lower perceived cancer control) predicts greater likelihood of anxiety risk. Lower masculine self-esteem predicts odds of depression risk. These findings elucidate the ways that PC patients’ perceptions of advancing disease and diminishing masculinity are linked to distress, thus identifying areas for psycho-educational and supportive interventions.