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.