Chronic stress impacts the prognosis of hepatocellular carcinoma patients after curative treatment by establishing a novel comprehensive classification: a cohort study and systematic review.

[AIMS] To investigate the impact of varying levels of chronic stress on the disease-free survival (DFS) and overall survival (OS) of patients with hepatocellular carcinoma (HCC) following curative treatment and establish a comprehensive evaluation index for chronic stress.

[METHODS] Ninety HCC patients who underwent curative treatment were assessed for chronic stress using hair cortisol concentration, Stress Score, and the Perceived Stress Scale (PSS-10). The optimal cut-off values for these markers were statistically determined, and correlations among them were analyzed to create the Chronic Stress Index (CSI), which classified patients into high or low chronic stress groups. DFS and OS were compared between the groups. Additionally, a systematic review of literatures on the effects of chronic stress and cancer recurrence was conducted.

[RESULTS] The optimal cut-off values of the Stress Score, PSS-10, and hair cortisol concentration were 15.30, 50.00 and 19.70 pg/mg, respectively. Patients with a CSI score of 3 to 4 were classified into the low chronic stress state (LCSS) group, whereas those scoring 5 to 6 were classified into the high chronic stress state (HCSS) group. Patients in the HCSS group had significantly reduced DFS (P < 0.001) and OS (P = 0.033) compared to the LCSS group. The systematic review identified only three clinical trials on chronic stress and cancer recurrence.

[CONCLUSION] High chronic stress levels are associated with shorter DFS and OS in HCC patients. The CSI classification effectively categorized the chronic stress state, providing a novel tool for clinical evaluation.