Prognostic significance of depressive symptoms in men with advance prostate cancer (PC): Results from the IRONMAN registry.

Abstract

139 Background: Depression is common in advanced PC and impacts quality of life. Whether depressive symptoms directly influence survival or serve as markers of disease progression remains unclear. We leveraged IRONMAN (International Registry of Men with Advanced Prostate Cancer) to examine how self-reported depressive symptoms at baseline and 6 months relate to survival in men with advanced PC. Methods: Eligible patients included those with newly diagnosed metastatic hormone sensitive (mHSPC) or castration resistant PC with (mCRPC) or without metastases (nmCRPC) (n=3378, 2017-2024) with baseline EORTC QLQ-C30 and EPIC-26 questionnaires. Patients were classified as “depressed” if a patient scored ≥3 on “Do you feel depressed?” on EORTC and ≥3 on “How big a problem ...feeling depressed?” on EPIC-26. The primary outcome was overall survival (OS) from study enrollment to death, withdrawal, or last follow-up; secondary outcome was PC–specific survival (PCSS). Average OS was estimated using restricted mean survival time (RMST), the association between changes in depressive symptoms and survival outcomes was assessed using Cox and Fine–Gray models. Results: At enrollment, 11% reported depressive symptoms (mHSPC 12%, mCRPC 10%, and nmCRPC 8%). Compared with non-depressed, depressed patients were younger (67 vs 70 years), more smokers (16% vs 9%), more often from Europe/Africa (47%/14% vs 38%/11%), had higher baseline PSA (197 vs 82 ng/ml) and more antidepressant use (14% vs 8%, p<0.001). Baseline depression predicted worse OS (HR 1.46, 95%CI 1.15–1.86). The risk of PC-specific death was increased by 34% (HR 1.34, 95%CI 1.01–1.78) in depressed patients. RMST was 3.5 years for depressed vs 3.8 years for non-depressed patients. Among mHSPC patients, RMST was 3.5 vs 5.1 years respectively, and among mCRPC, 2.9 vs 3.2 years. At 6 months (n=2295), 88% never experienced depression, 5% had resolved depression, 4% developed new depression, and 3% had persistent depression. New-onset self-reported depression was associated with worse OS (HR 2.13, 95%CI 1.52–2.97), with RMST of 2.6 vs 3.6 years in never depressed patients. Persistent depression trended toward worse OS (HR 1.31, 95%CI 0.86–1.99), while resolved depression was not associated with worse OS compared to non-depressed patients (HR 1.03, 95%CI 0.68–1.55). PSA rise (≥25% and 2ng/ml from baseline) occurred in 4.4% of never depressed, 1.2% of resolved, 9.1% of new, and 9.2% of persistent depression patients (p=0.024) and was associated with worse OS (HR 4.97, 95%CI 3.65-6.77) at 6 months. Conclusions: Self-reported depressive symptoms were common among men with advanced PC and were strongly linked to patient outcomes, highlighting the need for routine screening and early intervention in advanced PC care. Future research is needed to determine whether interventions to address mental health challenges could lead to improved PC outcomes.