Impact of postoperative chemotherapy on the prognosis of combined hepatocellular-cholangiocarcinoma: a retrospective study based on the SEER database

Background: The role of postoperative chemotherapy in the survival of combined hepatocellularcholangiocarcinoma (cHCC-CCA) remains undefined. This study investigated the impact of postoperative chemotherapy on patient survival. Methods: Patients with cHCC-CCA who underwent surgical resection between January 2004 and December 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into non-chemotherapy (n=138) and postoperative chemotherapy (n=59) groups. Survival analyses were performed using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Propensity score matching (PSM) was used to reduce selection bias. Results: Among 197 patients, median follow-up was 23 months. Median overall survival (OS) was 32 months [95% confidence interval (CI): 22.7-41.3], with 40 months (95% CI: 26.4-53.7) in the non-chemotherapy group versus 26 months (95% CI: 18.6-33.4) in the chemotherapy group; median cancer-specific survival (CSS) was 54 months (95% CI: 32.3-75.7) in the non-chemotherapy group versus 28 months (95% CI: 19.1-36.9) in the chemotherapy group. The 1-, 3-, and 5-year OS were 73.5%, 46.8%, and 37.4%, and CSS were 77.8%, 51.8%, and 43.8%, respectively. Postoperative chemotherapy did not significantly improve OS [hazard ratio (HR) =1.290, 95% CI: 0.850-1.956, P=0.20] or CSS (HR =1.420, 95% CI: 0.892-2.259, P=0.11) compared to no chemotherapy. Older age (51-74 vs. <= 50 years: HR =2.974, 95% CI: 1.243-7.118, P=0.01; >= 75 vs. <= 50 years: HR =4.097, 95% CI: 1.411-11.892, P=0.009) and higher T stage (T2 vs. T1: HR =1.972, 95% CI: 1.179-3.297, P=0.01; T3 vs. T1: HR =3.010, 95% CI: 1.586-5.713, P=0.001, T4 vs. T1: HR =3.628, 95% CI: 1.659-7.934, P=0.001) were associated with worse OS. Chemotherapy did not yield a survival benefit in any age or T stage subgroup (P>0.05), but subgroup analyses were limited by small sample sizes. In the multivariate analysis of 3-year OS, T stage was an independent factor, whereas postoperative chemotherapy showed no significant benefit. After PSM, 52 patients in each group were matched (n=104 total). There was still no significant difference in OS (HR =1.063, 95% CI: 0.646-1.749, P=0.81) or CSS (HR =1.148, 95% CI: 0.663-1.988, P=0.62) between the two groups. Conclusions: Our study did not find a significant association between postoperative chemotherapy and improved prognosis in cHCC-CCA patients. Older age and higher T stage were associated with worse prognosis. Prospective studies evaluating postoperative chemotherapy and other adjuvant strategies are needed to improve outcomes for this rare tumor.