Comparison of clinical characteristics and outcomes in patients with hepatocellular carcinoma based on serum alpha-fetoprotein status.

BACKGROUND: Alpha-fetoprotein (AFP) is the most commonly used and crucial tumor marker in clinical diagnosis and prognosis guidance for hepatocellular carcinoma (HCC). However, approximately 30% of HCC patients do not exhibit abnormal serum AFP levels at the time of diagnosis. This study aims to investigate the clinical characteristics and prognosis differences between AFP-negative and AFP-positive patients with HCC.

METHODS: Clinical data on patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Program were collected and analyzed. All patients with HCC were reported as AFP-negative or AFP-positive based on AFP test results. Overall survival (OS) and cancer-specific survival (CSS) were compared between the AFP-negative and AFP-positive patients. Logistic regression analysis and multivariable Cox regression analysis were performed to identify the association of AFP with tumor size, lymph node metastasis, distant metastasis, and CSS.

RESULTS: Of 7090 patients, 2074 (29.3%) and 5016 (70.7%) were AFP-negative and AFP-positive patients, respectively. The 5-year OS and CSS rates in AFP-negative patients were significantly better than AFP-positive patients (36.4 vs. 20.7% and 46.7 vs. 27.2%, both P  < 0.001). Logistic regression analysis revealed that the AFP level was an independent risk factor of tumor size [odds ratio (OR), 1.821; 95% confidence interval (CI), 1.625-2.040; P  < 0.001], N stage (OR, 1.922; 95% CI, 1.528-2.417; P   <  0.001) and M stage (OR, 2.435; 95% CI, 1.980-2.995; P  < 0.001). On multivariable Cox-regression analyses, AFP-positive was associated with decreased CSS (hazard ratio, 1.452; 95% CI, 1.355-1.557; P  < 0.001).

CONCLUSION: Abnormal serum AFP was significantly associated with worse prognosis, larger tumor size, more lymph node metastasis, and distant metastasis. Patients with AFP-positive may need more individualized treatment decision and further optimization of HCC management strategies.