Abstract
BACKGROUND AND AIMS: HCC frequently recurs after curative treatment, requiring surveillance with imaging and tumor markers. Some patients, however, present with persistent tumor marker elevation despite no radiologic recurrence evidence. This study evaluated outcomes following radiofrequency ablation (RFA) in such cases. METHODS: We retrospectively analyzed 1620 patients who achieved complete ablation for primary HCC during 1999-2015. Surveillance included quarterly imaging and serum tumor markers, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Patient characteristics at tumor marker elevation and recurrent HCC characteristics were compared between the early recurrence group (recurrence within 180 days of tumor marker elevation) and the late recurrence group (recurrence after 180 days of tumor marker elevation). We also estimated post-recurrence survival using the Kaplan-Meier method. RESULTS: Tumor marker elevation occurred in 907 cases in 509 patients. Recurrence was detected in 886 cases: 707 in the early and 179 in the late recurrence groups. The median (interquartile range) interval between marker elevation and recurrence was 89.0 (81.0-97.0) days. At tumor marker elevation, AFP ≥ 20 ng/mL was more frequent in the early versus late recurrence group (71.0% vs. 58.1%, p < 0.01), as was AFP ≥ 200 ng/mL (29.4% vs. 20.1%, p = 0.02). AFP-L3 ≥ 15% (60.0% vs. 62.6%, p = 0.58) and DCP ≥ 200 mAU/mL (19.7% vs. 16.2%, p = 0.34) showed no significant differences between groups. Recurrence patterns, including number of tumors, vascular invasion, distant metastasis, and tumor size, were comparable between groups. Local cure was achieved in 83.5% and 78.8% of the early and late recurrence groups, respectively, with no significant difference (p = 0.17). Median post-recurrence survival was 3.55 years for the early versus 3.31 years for the late recurrence group (p = 0.2). CONCLUSIONS: Even when HCC was undetected on imaging despite elevated tumor markers, many recurrence cases were subsequently detected, and curative treatment was possible through appropriate surveillance.