Preoperative depressive symptoms as an independent prognostic factor for long-term survival after curative-intent treatment for hepatocellular carcinoma: a prospective cohort study

BACKGROUND: Depression is common in cancer patients and may affect prognosis, yet its impact on long-term outcomes after curative-intent treatment for hepatocellular carcinoma (HCC) is underexplored. We prospectively examined whether preoperative depressive symptoms (Zung Self-Rating Depression Scale score ≥ 53) independently predict poorer overall survival (OS) and disease-free survival (DFS) in HCC patients undergoing curative-intent treatment. METHODS: A total of 213 pathologically confirmed HCC patients who underwent resection or ablation at Xiangya Hospital (2019) were enrolled. Depressive status was assessed by the Zung Self-Rating Depression Scale (cutoff≥53), dividing patients into screen-positive (n = 66) and screen-negative (n = 147) groups. The primary endpoint was OS; the secondary endpoint was DFS. Follow-up ended December 2025. Kaplan-Meier and Cox regression analyses adjusted for demographic, clinical, pathological, and treatment covariates. RESULTS: The screen-positive group included more females (21.2% vs. 10.9%, P = 0.05) and more patients with low educational attainment (69.7% vs. 52.4%, P = 0.04), whereas partner status and alcohol use were balanced. Median follow-up was 77 months. Depressive symptoms significantly worsened DFS (median 12.0 vs. 24.0 months; HR = 1.42, P = 0.02) and OS (median 41.0 vs. 55.0 months; HR = 1.78, P < 0.001). Multivariable Cox analysis confirmed depressive symptoms as an independent adverse factor for both DFS (HR = 1.45, 95% CI: 1.04-2.01, P = 0.03) and OS (HR = 1.50, 95% CI: 1.05-2.14, P = 0.03). The DFS model adjusted for age, partner status, BCLC stage, AFP, type of surgery, MVI, and Ki-67; the OS model additionally adjusted for educational attainment and alcohol use status. CONCLUSIONS: Preoperative depressive symptoms independently predict shorter DFS and OS after curative-intent treatment for HCC. Routine screening for depressive symptoms may help identify patients at higher risk; whether psychosocial intervention improves long-term outcomes requires further study.