Bone Metastasis of Hepatocellular Carcinoma: A Systematic Review on Presentation and Treatment Modalities

Author Type(s)

Student

Document Type

Abstract

Publication Date

10-2024

DOI

10.14309/01.ajg.0001036468.76420.e6

Journal Title

American Journal of Gastroenterology

Abstract

Introduction:

Hepatocellular Carcinoma (HCC) has the 3rd highest cancer-related mortality worldwide. The most common sites of metastasis include the lungs and peritoneum, with lower rates of bony metastasis. Extrahepatic spread is only present at diagnosis in 15% of patients. Bone metastasis has a reported incidence of 3-20%, with poor prognosis. In this systematic review, we have characterized and highlighted key features of bone metastasis in HCC to guide the diagnosis and management of this malignant sequela.

Methods:

A systematic literature search was conducted in MEDLINE, PubMed, and the Cochrane Library from 2000 - 2024. We included full-text abstracts and English articles describing a patient with HCC with bony metastasis at age >18. Patient demographics, history of cirrhosis and its etiologies, prior liver transplant, properties of the primary and secondary tumor, including the site of metastasis, treatment modalities, and mortality, were collected. Pooled data were assessed qualitatively and reported as mean±SEM.

Results:

We included 100 studies. The mean age was 60±13.5 years. 87% were male and 33% had a history of cirrhosis, 71% of whom had viral (HCV and HBV) followed by alcoholic cirrhosis at 21%. Initially, 1.8±1.2 lesions with a size of 6.7±0.8cm were detected as the primary tumor. The main sites of metastasis were the torso (52.1%) and the skull (39.5%). The interval from primary HCC to bony metastasis was 10.1±2 months with 52% diagnosed with the primary tumor. 65% of the primary HCC were treated through interventions (transplantation, hepatectomy, TACE, TAE, and PEIT) followed by chemotherapy at 27% and radiation at 20%. Metastatic therapy involved 31% surgical intervention (resection, TACE, TAE), radiation at 27% and chemotherapy at 24%. The average 1 and 5-year survivals were 43.5% and 11.7%.

Conclusion:

Our study demonstrates axial skeleton preference for bone metastases in HCC with an approximate 10-month gap between primary and metastatic HCC diagnosis. This suggests high rates of treatment failure in HCC given no standard protocol and a high rate of skeletal-related events (SRE), including pathologic fractures and the need for radiation or surgical intervention to bone. As such, the 5-year mortality in HCC remains noticeably low. To guide the formation of novel treatment pathways, future larger-scale studies are needed to compare and stratify risk reduction in mortality and SREs in response to various therapeutic modalities for primary HCC and bone metastases.

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