What are the treatment options for stage one hepatocellular carcinoma to reduce mortality?

Treatment Options for Stage One Hepatocellular Carcinoma to Reduce Mortality

Surgical resection is the first-line treatment for stage one HCC in patients with solitary tumors and well-preserved liver function (normal bilirubin, hepatic venous pressure gradient ≤10 mmHg, or platelet count ≥100,000), achieving 5-year survival rates of 50-68% with perioperative mortality of 2-3% in cirrhotic patients. 1, 2

Primary Curative Treatment Options

Surgical Resection

• Resection is recommended for patients without advanced fibrosis when R0-resection can be achieved without causing postoperative liver failure. 2
• In cirrhotic patients, resection is effective and safe (postoperative mortality <5%) in early BCLC stages (0 and A) provided there is a single lesion, good performance status, and no clinically significant portal hypertension. 2
• The 5-year survival rate after resection ranges from 50-68% in experienced centers, though recurrence rates remain high at 50-70%. 2, 3
• Patient selection must be based on Child-Pugh classification: Child-Pugh class A patients are good candidates, while Child-Pugh class C patients should not undergo resection due to risk of liver failure. 2

Liver Transplantation

• Liver transplantation should be considered as first-line treatment for patients meeting Milan criteria (single tumor <5 cm or ≤3 nodules ≤3 cm) who are not suitable for resection due to impaired liver function. 1, 2
• Living donor liver transplantation achieves 1-, 3-, and 5-year survival rates of 85%, 75%, and 70%, respectively, with perioperative mortality of approximately 3% and one-year mortality ≤10%. 2, 1
• For patients with decompensated cirrhosis within Milan criteria, transplantation is the preferred option as it treats both the tumor and underlying cirrhosis. 2
• In Japan, expanded criteria (5-5-500 rule: tumor ≤5 cm, ≤5 nodules, AFP ≤500 ng/mL) have been validated with 5-year recurrence rates <10%. 2

Local Ablation Therapies

• Radiofrequency ablation (RFA) or microwave ablation (MWA) is recommended for tumors ≤3 cm in very early HCC (BCLC 0), particularly for single nodules <2 cm or patients not suitable for resection. 1, 2
• RFA provides superior local control compared to percutaneous ethanol injection (PEI), especially for tumors >2 cm. 2
• The number and diameter of lesions treated by RFA should not exceed five nodules and 5 cm, respectively. 2

Treatment Selection Algorithm

Step 1: Assess Liver Function and Portal Hypertension

• Evaluate Child-Pugh classification, hepatic venous pressure gradient, platelet count, and bilirubin levels. 1, 2
• Check for clinical signs of portal hypertension including varices, ascites, and portal hypertensive gastropathy. 2

Step 2: Determine Tumor Characteristics

• Confirm single tumor status and size through dynamic CT or MRI showing arterial hypervascularity with portal/delayed phase washout. 2
• Assess for vascular invasion and extrahepatic spread. 2

Step 3: Select Treatment Based on Combined Assessment

• If Child-Pugh A, single tumor, no portal hypertension, adequate future liver remnant (≥20-40% of total liver volume): Proceed with surgical resection. 2, 1
• If Child-Pugh A-B with decompensated cirrhosis, tumor within Milan criteria: Prioritize liver transplantation. 1, 2
• If tumor ≤3 cm and resection not feasible: Perform RFA or MWA. 1, 2
• If anticipated transplant waiting time >6 months: Consider bridging therapy with resection, local ablation, or TACE to prevent tumor progression. 2

Critical Considerations and Pitfalls

Anatomic vs. Non-Anatomic Resection

• Anatomic resection is recommended when tumor invades segmental portal branches or has satellite lesions, as it provides better recurrence-free survival. 2
• Intraoperative ultrasound should be used to detect tumor vessels and lesions missed on preoperative imaging. 2

Future Liver Remnant Assessment

• Portal vein embolization (PVE) can be utilized preoperatively to induce hypertrophy of the remnant liver when the anticipated remnant is insufficient. 2
• The minimum safe remaining liver parenchyma ranges from 20-40% of total liver volume. 2

Adjuvant Therapy

• Neo-adjuvant or adjuvant therapies are NOT recommended to improve outcomes after resection or local ablation. 2

Biopsy Indications

• Biopsy is NOT indicated when: (1) patient is not a candidate for therapy due to serious comorbidity; (2) decompensated cirrhosis patient is on transplant waiting list; (3) patient is a candidate for resection with acceptable morbidity/mortality risk. 2

Follow-Up Protocol

• Patients undergoing curative resection should be followed every 3-6 months with AFP determination and liver imaging for at least 2 years, as curative therapy can still be offered at relapse. 2, 3
• Response assessment should be based on dynamic CT or MRI using modified RECIST criteria. 1, 4

Important Caveats

• The 5-year recurrence rate after resection remains 50-70% even for small HCC (<2 cm) without microvascular invasion. 2
• Risk factors for recurrence include macro/microvascular invasion, multifocal tumors, and high alpha-fetoprotein levels. 2
• Regional lymph node metastases are associated with significantly decreased survival. 2
• Child-Pugh C patients should receive only supportive care, not surgical intervention. 2, 1