Abstract
Depression is a prevalent but often underrecognized comorbidity among cancer patients. Emerging evidence suggests that psychological distress may adversely impact cancer outcomes, but the magnitude of its effect on survival remains unclear. This meta-analysis evaluates the association between depression diagnosed after cancer diagnosis and cancer-specific and all-cause mortality across major cancer types. A systematic search of PubMed, Web of Science, Google Scholar, and the Cochrane Library was conducted to identify cohort studies examining the impact of depression on cancer mortality. Studies were included if they assessed clinically diagnosed depression or depressive symptoms using validated scales and reported hazard ratios (HRs) for mortality outcomes. A random-effects meta-analysis was performed to pool HR estimates, with heterogeneity assessed via Cochran's Q and I(2) statistics. Funnel plots and Egger's test were used to evaluate publication bias. A total of 65 cohort studies were included. Depression was associated with significantly increased cancer-specific mortality in colorectal cancer (HR 1.83, 95% CI 1.47-2.28), breast cancer (HR 1.23, 95% CI 1.13-1.34), lung cancer (HR 1.59, 95% CI 1.36-1.86), and prostate cancer (HR 1.74, 95% CI 1.36-2.23). When considering mixed cancer types, depression was linked to a 38% increased risk of cancer mortality (HR 1.38, 95% CI 1.20-1.60). Significant heterogeneity was observed across studies (I(2) range 56-98%), suggesting variations in study populations and methodologies. Sensitivity analyses confirmed the robustness of the findings, and trial sequential analysis indicated sufficient evidence for a conclusive association. Depression after cancer diagnosis is associated with a significantly increased risk of cancer-specific mortality across multiple cancer types. These findings highlight the urgent need for integrating routine mental health screening and interventions into oncology care. Future research should focus on mechanistic pathways and targeted interventions to mitigate the negative impact of depression on cancer survival.