Abstract Introduction Prostate cancer (PCa), erectile dysfunction (ED), and urinary incontinence (UI) can all independently increase a person’s risk of mental health (MH) disorders. However, the relationship between ED and UI on the MH of PCa patients is poorly understood. Objective Our objective is to assess the impact of ED and UI on MH in PCa patients at different stages of diagnosis and treatment. Methods We performed a retrospective cohort study using the insurance claims database, IBM MarketScan, between 2011-2020. Using ICD9/10 and CPT codes, we identified all patients with a diagnosis of PCa and matched each to a control without PCa by age and CCI, which was modified to exclude cancer diagnoses. PCa status was categorized into four groups based on where patients were in their prostate cancer timeline: pre-cancer (PCa patients prior to diagnosis), watching (patients with a diagnosis of PCa without treatment), radiation and prostatectomy. We also noted the first diagnosis of UI and ED for each patient. Patients were followed throughout their enrollment period and any MH diagnoses were recorded, including depressive disorders, anxiety disorders, psychotic disorders, substance abuse disorders and self-harm/suicide attempts. Multivariable cox proportional hazard models were used to assess the relationship between PCa, ED or UI, and MH diagnoses. Models additionally controlled for age, rurality and comorbidities. Patients were censored when their enrollment ended. Interaction terms between PCa status and ED or UI were included to test for differential responses to urologic comorbidities between cancer patients and cancer-free controls. Results A total of 1,253,618 patients were included in the analysis. All patients in the pre-cancer, watching, prostatectomy, and radiation groups without ED or UI showed a decreased risk of being diagnosed with a MH condition compared to controls [HR: 0.86 (0.84-0.88), 0.93 (0.92-0.94), 0.77 (0.74-0.81), and 0.89 (0.86-0.93), respectively; p<0.001]. MH diagnosis was significantly increased in controls with ED [HR: 1.13 (1.10-1.15); p<0.001]. Though the effect of ED was increased in the pre-cancer group [HR: 1.05 (1.00-1.11); p<0.05] compared to controls, the effect was significantly ameliorated in the watching, prostatectomy and radiation groups [HR: 0.88 (0.85-0.90), 0.91 (0.85-0.98) and 0.88 (0.82-0.95), respectively; p<0.01]. UI also significantly increased the likelihood of a MH diagnosis in controls [HR: 2.07 (2.00-2.15); p<0.001], but the effect was significantly dampened for men in the pre-cancer, watching, prostatectomy and radiation groups [HR: 0.83 (0.76-0.91), 0.67 (0.64-0.71), 0.54 (0.50-0.58), and 0.69 (0.62-0.77), respectively; p<0.001). Conclusions Compared to age and CCI-matched controls, PCa patients with ED in watching, prostatectomy and radiation groups and PCa patients with UI have a decreased risk of being diagnosed with a MH condition compared to controls with the same urologic comorbidities. This relationship between PCa groups and MH disorders has been observed in other cancer patient populations and is sometimes referred to the “cancer paradox” or “post-traumatic growth” since these patients with cancer experience a lower incidence of MH compared to those without cancer. Possible reasons for this phenomenon include enhanced resilience, a reevaluation of life priorities and/or a greater appreciation for life due to a shift in perspective of cancer patients. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Inherent bio, Paterna bio, Firmtech, Turtle health, Maximus, Carrot.