Extrahepatic metastases occur in a minority of hepatocellular carcinoma patients treated with locoregional therapies: analyzing patterns of progression in 285 patients

Abstract

Although most cancers are considered predominantly systemic processes, this may not hold true for hepatocellular carcinoma (HCC). The literature regarding patterns of progression of HCC (local versus systemic) has been relatively sparse. Our objectives were to: (1) analyze patterns of progression in HCC patients presenting with intrahepatic disease from initial treatment until death, and (2) identify clinically relevant risk factors for the development of metastases. Over a 9-year period, 285 patients treated with transarterial locoregional therapies underwent scheduled imaging follow-up from treatment until death and were categorized by pattern of progression: (i) intrahepatic (increased tumor enhancement/size, development/progression of vascular invasion, new hepatic lesions) progression or (ii) extrahepatic (adrenal/bone/lung/lymph node) metastases. Uni/multivariate analyses assessing the risk factors for the development of metastases were performed. The median time from last scan to death was 2.4 months (interquartile range: 1.3-4.8 months). The time to development of metastases, vascular invasion, and/or new lesions was 13.8 months (confidence interval: 11.3-17.7 months). Of the 209 patients followed until death, only 50 developed extrahepatic metastases (24%). Multivariate analyses identified age <65 years (P = 0.038), alpha-fetoprotein >200 ng/mL (P = 0.04), and vascular invasion (P = 0.017) as significant predictors of metastases development.

Conclusion: Knowledge of the risk factors associated with the development of metastases may help guide assessment of patient prognosis. Because 76% of patients presenting with local disease treated with locoregional therapies die without developing extrahepatic metastases, the notion of HCC as a systemic disease, as detected by imaging, may be reconsidered.

Figure 1. Patterns of Progression by Child-Turcotte-Pugh

Intrahepatic progression: This includes new lesions, progression of tumors by EASL or WHO guidelines, development of PVT or, progression of pre-existing PVT. Note: patients were stratified by intrahepatic and extrahepatic progression. Among patients with intrahepatic progression, the sum of modes of progression (i.e. Treated Lesion(s) + New Lesions + PVT) maybe greater than total intrahepatic progressors since patients may progress by multiple methods. Abbreviations: MS: Median survival; mo: months; CTP: Child-Turcotte-Pugh; PVT: Portal vein thrombosis

Figure 2. Patterns of Progression by BCLC

Intrahepatic progression: This includes new lesions, progression of tumors by EASL or WHO guidelines, development of PVT or, progression of pre-existing PVT. Note: patients were stratified by intrahepatic and extrahepatic progression. Among patients with intrahepatic progression, the sum of modes of progression (i.e. Treated Lesion(s) + New Lesions + PVT) maybe greater than total intrahepatic progressors since patients may progress by multiple methods. Abbreviations: MS: Median survival; mo: months; CTP: Child-Turcotte-Pugh; PVT: Portal vein thrombosis