Background and Aim: For intermediate stage Hepatocellular carcinoma (HCC) patients, transarterial chemoembolization (TACE) is first-line recommended treatment option. However, intermediate stage is comprised of heterogeneous population, and some suggested that systemic treatment might be a first-line option for intermediate stage HCC in the era of multiple and potent systemic treatment options. Patients who shows rapid progressive disease (rapid PD) despite TACE might be candidate, hence, we analyzed incidence and risk factors for rapid PD in intermediate stage HCC treated with TACE.
Methods: A total of 226 patients with intermediate stage HCC who underwent treatment with TACE and showed PD between January 2007 and December 2012 were analyzed. Rapid PD was defined for patients who showed PD, defined by mRECIST criteria, within 90 days after first TACE treatment.
Results: Rapid PD was identified in 19.0% of patients (43/226 patients). Progression type of rapid PD group were mainly stage progression. Proportion of patients with extrahepatic metastasis and/or vascular invasion was 65.1% (28/43 patients) among rapid PD group. Overall survival was worse in rapid PD group (median 1.1 vs. 3.3 years, p <0.001). When compared, alpha-fetoprotein (AFP) titer over 2000 ng/ml, protein induced by vitamin K absence or antagonists II (PIVKA-II) titer over 1000 mAU/ml, tumor size over 5cm to 10cm and tumor size more than 10cm were independent factors associated with rapid PD. When stratified by identified risk scores, proportion of patients with rapid PD were 40.7%, 28.3%, 21.3% and 9.7% for patients with number of risk score zero, one, two and three or more, respectively. We selected rapid PD criteria as risk score three or more and it can be a tumor size over 10cm with one high tumor marker or tumor size 5-10cm with 2 high tumor markers. When compared, rapid PD criteria showed higher discrimination rate on rapid progression rate as well as overall survival than other previous criteria.
Conclusions: Among intermediate stage HCC patients, about 20% experienced rapid PD despite TACE. Pattern of PD were vascular invasion or extrahepatic spread in about 65% of rapid PD group. We suggest rapid PD criteria, a combined criteria of tumor size with two tumor marker, and is simple and easy to use. Selected patients who are in rapid PD criteria, a tumor size over 10cm with one high tumor marker or tumor size 5-10cm with 2 high tumor markers, might be considered as a candidate of early or first-line systemic treatment or clinical trials. This warrants further evaluation.