During the meeting, Prof. Dongping Pan and Dr. Kingham from the Queen Mary Hospital in Hong Kong, China, provided some insights for us to think about the treatment modalities of small liver cancer. They presented that due to the lack of data from randomized studies comparing the efficacy of different treatments for small liver cancer, they are not directly comparable like apples, oranges and pears. The following discussion analyzes the efficacy of various treatment modalities for small liver cancer based on the findings presented at the meeting.
Liver Transplantation
Indications for liver transplantation include malignant liver disease and underlying parenchymal liver disease and are not limited by liver function, but are limited by the extent of the tumor (size and number, by Milan criteria) and the number of donors. Analysis of liver transplantation outcomes using different inclusion criteria showed that liver transplantation was better in patients with strict inclusion criteria (UNOS stage T2) and that liver transplantation was the best option for those with comorbid cirrhosis; however, if the waiting time for a liver source was >6 months, then the disease could progress, thus depriving the patient of liver transplantation, and its treatment outcome may not be superior to surgical resection and it is better to withdraw them from the liver transplant list.
Shah et al. compared the efficacy of surgery versus liver transplantation for the treatment of small hepatocellular carcinoma (Milan criteria) and found that surgical resection (121 cases) versus liver transplantation (140 cases) had no significant effect on patient survival; however, when grouped by waiting time for liver source < 4 months, patients who received liver transplantation (64 cases) had better survival than those who underwent surgical resection (121 cases).
Surgical resection
Surgical resection is the most effective treatment for small hepatocellular carcinoma and is more widely used clinically than liver transplantation, with no specific limitations on tumor size or adjacent vessels, and complete resection of the tumor can be achieved if sufficient liver reserve is available. However, surgery is mostly limited by the patient’s liver function and tumor extent, and its effect is better for single tumor confined to a single lobe of the liver with normal or almost normal liver function, but the reserve function of the residual liver cannot be ignored. The problems of surgical treatment of small hepatocellular carcinoma are mainly focused on the following aspects.
Possible causes of postoperative death
Common causes of postoperative patient death include: liver with inadequate functional reserve, slow regenerative repair to normal or missing; combined portal hypertension with risk of hemorrhage during resection; hepatic encephalopathy caused by extensive resection, increased portal blood flow causing liver loss, ascites, variceal bleeding; complications caused by liver failure, etc.
Case selection for surgical resection
Multiple foci suggesting the presence of intrahepatic metastases synchronized with the primary tumor are traditionally a contraindication to surgery. Generally this group has a high recurrence rate after surgery and a poor prognosis (5-year survival rate <25%), but the selection of appropriate cases can improve the treatment outcome. There have been reports showing a slight increase in postoperative complications in patients due to a reduction in the proportion of extensive surgical resections, but a decrease in blood transfusions and a significant reduction in mortality.
Improving surgical resection outcomes
Factors that may improve surgical outcomes include selection of cases with appropriate tumor extent, adequate preoperative evaluation of patient liver function, and improved surgical technique. In addition, the use of strategies to preserve liver parenchyma, preoperative percutaneous portal vein embolization, increasing the volume of normal liver lobes and thus increasing the proportion of lobar resections, and reducing the risk of liver failure may also reduce surgical mortality.
One study investigated the efficacy of different resection patterns for solitary limited hepatocellular carcinoma ≤5 cm. The results showed that those with wider tumor resection margins (≥2 cm) had significantly better 5-year survival rates than those with narrower tumor resection margins (<1 cm), 75% and 49%, respectively (P=0.008). Moreover, the follow-up results showed a higher percentage of margin recurrence in those with narrow resection margins compared to those with wider resection margins (30% vs. 0).
The results of a previous study suggested that preoperative portal embolization significantly improved the incidence of liver failure (7% versus 50%, P=0.01) and length of hospital stay (13±4 days versus 30±15 days, P=0.0002) in patients with small hepatocellular carcinoma who were prepared for right lobe resection.
Ablation and its comparison with surgery
For percutaneous RFA or microwave ablation, factors such as tumor size (>5 cm), location (large blood vessels and other structures adjacent to their peripheral regions), and large tumor load (multiple foci) limit its efficacy. In addition, investigators have found, after short-term follow-up, that complications accompanying inadequate ablation can cause patient death.
In 2005, Mulier statistically reported the efficacy of RFA in 4424 patients with liver cancer. The results of an analysis of factors influencing local tumor recurrence showed that the recurrence rate increased as the tumor grew larger and was significantly higher in tumors located under the hepatic tegument or adjacent to large blood vessels.
In addition, the results of two randomized controlled studies [Huang (Huang), 2005; Chen (Chen), 2006] suggest that the efficacy of RFA is similar to that of surgery for small hepatocellular carcinoma. In 2010, Huang et al. reported that the 5-year recurrence-free survival (51% vs. 29%, P=0.017) and 5-year survival (76% vs. 55%, P=0.001) were better in the surgery group than in the RFA group after RFA or surgery for small hepatocellular carcinoma meeting the Milan criteria.
Summary
In small hepatocellular carcinoma, all three treatment options (liver transplantation, surgery, and ablation) can achieve some efficacy. Among them, RFA is the first-line treatment for <3 cm tumors; surgery is the most effective treatment for larger tumors for the largest number of people, and liver transplantation is feasible and advantageous after recurrence; and liver transplantation is the best treatment option for those with progressive cirrhosis or multiple tumor lesions.
Tips
Definition of small liver cancer: United Network for Organ Sharing (UNOS) stage T2 criteria: single tumor (2-5 cm) or 2-3 tumors (largest tumor < 3 cm). Milan criteria: single tumor (≤ 5 cm) or ≤ 3 tumors (≤ 3 cm each) without vascular invasion.