Pattern of progression and post-progression survival following transarterial embolisation: An analysis of the TACE-2...

Previous studies have demonstrated that the pattern of progression (POP) following systemic therapy or transarterial radioembolisation is prognostic for post-progression overall survival (PPOS). POP has therefore been proposed as a stratification factor for subsequent clinical trials. However, its significance in TACE-treated populations has not been prospectively explored. We analysed the impact of POP on PPOS in patients treated in the TACE-2 and TACTICS trials.

TACE-2 and TACTICS are two prospective, multicentre, randomised trials comparing TACE plus sorafenib with TACE plus placebo, conducted in the UK and Japan, respectively. Patients with radiological progression in both trials were included in this analysis. POP was defined as: target or non-target lesion progression (TNTLP), new intrahepatic lesions (NIH), or new extrahepatic lesions (NEH). As extrahepatic disease was an exclusion criterion in both trials, only intrahepatic lesions qualified for the TNTLP group. PPOS was assessed using the Kaplan-Meier method, and comparisons were performed using the log-rank test.

A total of 285 patients were included (86 with TNTLP, 167 with NIH, and 32 with NEH). Median PPOS was 24.8 months for TNTLP, 18.7 months for NIH, and 7.0 months for NEH. Compared with the TNTLP group, patients with NEH had significantly worse survival (adjusted hazard ratio 3.05, 95% CI 1.88-4.94; p <0.001), whereas survival in the NIH group was not significantly different (adjusted hazard ratio 1.21, 95% CI 0.88-1.65; p = 0.24). No survival differences were observed between placebo and sorafenib arms within each POP group.

Progression in the form of new extrahepatic disease following TACE occurred in only 11% of patients but was associated with poor overall survival, reinforcing the importance of extrahepatic disease as a stratification factor in clinical trials.

Pattern of progression has been validated as a significant independent prognostic factor for post-progression overall survival in patients with hepatocellular carcinoma (HCC) treated with systemic anticancer therapies and selective internal radiation therapy. This study is the first prospective multicentre analysis to demonstrate that pattern of progression is also a significant independent prognostic factor for post-progression overall survival in patients with HCC treated with transarterial chemoembolisation. Future trials of locoregional therapies for HCC should report pattern of progression and consider its use as a stratification factor in subsequent studies.