Can hepatocellular carcinoma (HCC) metastasize to bone?

Bone Metastasis in Hepatocellular Carcinoma

Yes, hepatocellular carcinoma (HCC) can and does metastasize to bone, with bone being one of the most common sites of extrahepatic metastasis in advanced HCC. The prevalence of bone metastasis in HCC patients ranges from approximately 3-13% at initial diagnosis, with higher rates observed in patients with advanced disease 1, 2.

Epidemiology and Clinical Significance

• Bone metastases occur in approximately 4.29% of newly diagnosed HCC patients 2
• The incidence of bone metastases in HCC has increased in recent decades, partly due to improved survival of HCC patients allowing more time for metastatic disease to develop 3
• Median survival after diagnosis of bone metastasis is approximately 7-11.7 months 1, 4

Common Sites and Characteristics

• Most common sites of bone metastasis in HCC:

  • Spine (59.7% of cases) 1
  • Pelvis
  • Ribs
  • Skull 3

• Radiographic characteristics:

  • Predominantly osteolytic lesions (82.4-100% of cases) 1, 5
  • Frequently associated with soft tissue mass formation (68.6%) 5
  • Vertebral body involvement in 87.8% of vertebral metastases 5
  • Vertebral appendix metastasis can occur independently of vertebral body involvement 5

Risk Factors for Bone Metastasis in HCC

Several factors are associated with increased risk of bone metastasis:

• Male sex
• Higher T stage of primary tumor
• Lymph node involvement
• Presence of intrahepatic metastases
• Portal vein thrombosis (found in approximately 50% of patients with bone metastases) 2, 3
• Child-Pugh score (higher scores correlate with shorter time to bone metastasis) 1

Diagnostic Approach

For patients with suspected bone metastasis from HCC:

1. Bone scan is recommended if bone metastasis is clinically suspected 6
2. CT or MRI of specific bone sites for confirmation and detailed assessment 6
3. FDG PET-CT may be considered, particularly prior to curative treatments, with reported sensitivity of 100% for bone metastases from HCC 6

Clinical Management

1. Pain management:

   • Acetaminophen is the preferred analgesic (up to 3g/day) 6
   • Avoid NSAIDs due to risk of gastrointestinal bleeding, ascites decompensation, and nephrotoxicity 6
   • Opioids for moderate-to-severe pain with concurrent laxative program to prevent constipation and hepatic encephalopathy 6

2. Local treatment for bone metastasis:

   • External beam radiotherapy is recommended for pain control in patients with bone metastases 6
   • Palliative radiotherapy (median dose 40 Gy) provides pain response rates of 81% 6
   • Consider single-session palliative radiation for patients with shortest expected prognosis 6
   • Radiotherapy should be considered for lytic bone metastases at high risk of fracture, especially in weight-bearing bones 6

3. Systemic therapy:

   • Bisphosphonate therapy (zoledronic acid) is commonly used (88.5% of patients) 1
   • Sorafenib remains the standard systemic therapy for advanced HCC with preserved liver function 6

Surveillance and Prevention of Complications

Early detection of bone metastases is crucial as it can reduce the risk of skeletal-related events:

• Fractures or paralysis occur in approximately 13.2% of patients with bone metastases 4
• The risk of fractures/paralysis is significantly higher in patients diagnosed based on symptoms (20.9%) compared to those diagnosed through surveillance (3.0%) 4
• Regular surveillance imaging may help detect bone metastases before symptomatic presentation, potentially preventing complications 4

Prognostic Factors

Factors associated with shorter survival after bone metastasis diagnosis:

• Age over 75 years
• HCV etiology
• Child-Pugh class B/C 4
• Poor ECOG performance status 1
• Site of bone metastasis (more than the number of lesions) significantly impacts survival 1

Early detection and appropriate management of bone metastases in HCC patients are essential to prevent complications like fractures and paralysis, which significantly impact quality of life, even if they may not directly affect overall survival.