by Dr.C.H. Weaver M.D. updated 8/2019
The liver is a common place for several types of cancer to spread, once the disease has become advanced. The spread of cancer to the liver is referred to as liver metastasis. Cancers originating in the pelvis or abdomen tend to have the higher rates of liver metastasis.
Treatment of liver metastases with chemotherapy rarely produces a durable complete remission leading researcher to develop liver directed therapies to be used alone or in combination with systemic treatment. (1) Several therapeutic options exist for the treatment of liver metastases.
- Surgery to remove the metastasis
- Radiofrequency ablation
- Radiation beads
Surgery and radiofrequency ablation are among the most commonly used types of treatment for liver metastases
About Radiofrequency Ablation
Radiofrequency ablation entails the use of an electric current that is passed into a target area (tumors of the liver) through a needle probe. Heat is generated by the electric current at the site of the tumor, which ultimately destroys cancer cells. The procedure works as follows: conventional imaging methods, such as ultrasound, a computerized tomography (CT) scan, or magnetic resonance imaging (MRI) are utilized to guide the physician in the placement of the needle probe into the cancer. An electrical current is then generated and passed through the probe directly into the cancer cells. These cancer cells are heated by the electrical current to the point of irreversible ablation (destruction). Angio-CT involves the injection of a dye into the main artery of the liver prior to a CT scan (angio-CT). The dye enhances the contrast on CT scans, allowing physicians to visualize the small masses of cancer cells.
RFA may also be performed during surgery. The high-energy waves heat the cancer cells such that they later become coagulated and are destroyed. RFA is a useful addition to systemic chemotherapy or precision cancer medicines in patients with colorectal cancer and liver metastases.
RFA as Effective as Surgery?
Researchers from France conducted a clinical trial to compare the rates of local recurrences following intraoperative RFA or surgery in the treatment of liver metastasis. This trial included 88 patients who were treated with intent to cure with either RFA or surgery to remove their liver metastases. Patients with large metastases, or small metastases that were located on the periphery of the liver were treated with surgery, and patients with small metastases that were located in the central area of the liver were treated with RFA. There was an average of approximately 5 liver metastases that were treated per patient. The average follow-up was nearly 28 months. Local recurrences occurred in 5.7% of patients treated with RFA, 7.1% of patients with small metastases located on the periphery of the liver and treated with surgery, and 12.5% of patients with large metastases who were treated with surgery.
Surgical Removal of Single Site of Cancer Spread to Liver Improves Survival Compared to RFA in Colorectal Cancer
The surgical removal of a single site of cancer that has spread to the liver improves survival compared to RFA among patients with advanced colorectal cancer.
Researchers from the M.D. Anderson Cancer Center analyzed data from patients with colorectal cancer who had only one site of liver metastasis with no cancer spread elsewhere in the body. Patients were either treated with surgery (hepatic resection) to entirely remove the cancer and surrounding tissue or with RFA. This study included 180 patients; 50 of whom underwent hepatic resection and 30 of whom underwent RFA.
- At five years, recurrences near or at the site of the liver metastasis occurred in just 5% of patients treated with surgery, compared with 37% of patients treated with RFA.
- Survival at five years was 71% for those who underwent surgery, compared with only 27% for those who underwent RFA.
The researchers concluded that it appears that hepatic resection for patients with colorectal cancer whose cancer has only spread to a single site in the liver appears to significantly improve survival when compared to treatment with RFA.
RFA Most Effective with Smaller Metastases
In a report of 135 individuals with liver metastases who underwent laparoscopic RFA patients who had a blood marker known as CEA that measured less than 200ng/ml had a greater survival advantage than those patients whose CEA was greater than 200ng/ml and the size of the liver lesions was also correlated with survival. Patients with smaller lesions (less than 3cm) had an average survival of 38 months; patients with medium lesions (3-5 cm) had an average survival of 34 months; and patients with large lesions (greater than 5 cm) had an average survival of 21 months. Multiple lesions also affected the overall survival. The presence of 1-3 tumors resulted in a survival period of 29 months, compared to 22 months for patients who had more than 3 tumors.
Chemoembolization and RFA is more effective than either treatment alone.
Transarterial chemoembolization (TACE) is designed to stop blood flow to the tumor. The lack of blood supply deprives the tumor of needed oxygen and nutrients, causing cell death. The blood flow is stopped by using small particles saturated with chemotherapy drugs that soak the tumor in chemotherapy for a prolonged period.
Researchers in China conducted a study in 291 patients diagnosed with liver cancer larger than 3 centimeters. Patients were randomly assigned to receive treatment with either TACE alone, RFA alone, or a combination of TACE and RFA. The goal of the study was to evaluate survival benefits as well as response rates to these various techniques.
- After an average follow up of 28.5 months, the average survival times were 24 months among the patients who received TACE, 22 months for patients who received RFA, and 37 months among those who received TACE and RFA.
- Further analysis revealed that treatment of multiple tumors within the liver with combination therapy produced better outcomes than treatment of single tumors with RFA or TACE alone.
- Response rates that were sustained for six months were highest among patients treated with TACE and RFA (54%) compared with 35% for patients treated with TACE alone and 36% among patients treated with RFA alone.
Patients with larger liver tumors, a combination of TACE and RFA was successful in improving overall survival outcomes.
Patients with liver metastases should be seen at a cancer center that provides RFA, TACE or other liver directed therapies and speak with their physician about the risks and benefits of RFA or the participation in a clinical trial further evaluating RFA or other promising therapeutic approaches.
- Benoist S, Brouquet A, Penna C, et al. Complete Response of Colorectal Liver Metastases After Chemotherapy: Does It Mean Cure? Journal of Clinical Oncology. 2006; 24:3939-3945.
- Elias D, Baton O, Sideris L, et al. Local recurrences after intraoperative radiofrequency ablation of liver metastases: a comparative study with anatomic and wedge resections. Annals of Surgical Oncology. 2004; early on-line publication. Available at: http://www.annalssurgicaloncology.org/cgi/content/abstract/ASO.2004.08.019v1. Accessed April 2004.
- Aloia T, Vauthey J-N, Loyer E, et al. Solitary Colorectal Liver Metastasis: Resection Determines Outcome. Archives of Surgery. 2006; 141:460-467.
- Berber E, Pelley R, Siperstein A, et al. Predictors of Survival After Radiofrequency Thermal Ablation of Colorectal Cancer Metastases of the Liver: A Prospective Study. Journal of Clinical Oncology.2005; published online ahead of print January 31, 2005.
- Cheng, B., Jia, C., Liu C., et al. Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3cm. Journal of the American Medical Association. 2008; 299(14): 1669-1677
Better Survival but More Complications After Radiofrequency Thermal Ablation of Small Liver Cancers
According to an article in the journal Gut, treatment of small liver cancers with radiofrequency thermal ablation resulted in fewer recurrences and longer survival, but also more complications, than treatment with ethanol or acetic acid injections.
The liver is the largest organ in the body and is responsible for over 500 functions. These include the secretion of glucose, proteins, vitamins, and fats; the production of bile; the processing of hemoglobin; and detoxification of numerous substances. Primary liver cancer starts in the cells of the liver and can spread through blood or lymph vessels to different parts of the body. Approximately 85% of all liver cancers that start in the liver (primary liver cancer) are classified as hepatocellular carcinoma.
Surgical removal of the cancer is the treatment of choice for small liver cancers, but others options may be considered for patients who decline surgery or who have inoperable cancer. This study compared three alternative approaches to destroying small liver cancers: radiofrequency thermal ablation (use of electric current to destroy cancer cells); ethanol injection (injection of alcohol into the tumor to kill cancer cells); and acetic acid injection (injection of acetic acid, the primary acid in vinegar, into the tumor to kill cancer cells). Each of these approaches involves the placement of a probe through the skin and into the cancer. The prone is guided by imaging such as computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound.
Investigators from Taiwan conducted a randomized clinical trial to compare these three approaches among a total of 187 adult patients with hepatocellular carcinomas measuring three centimeters or less. Sixty-two patients were treated with radiofrequency ablation, 62 were treated with ethanol injection, and 63 were treated with acetic acid injection. After three years of follow-up, cancer recurred in 14% of those treated with radiofrequency ablation, 34% of those treated with ethanol, and 31% of those treated with acetic acid. Survival was also better in the radiofrequency ablation group: 74% survived for at least three years after treatment, compared to 51% of the ethanol group and 53% of the acetic acid group. However, major complications were also more common in the patients receiving radiofrequency ablation. Two of these patients developed a hemothorax (blood in between the chest wall and the lung), and one had a perforation of the stomach (a hole through the wall of the stomach). There were no major complications among patients receiving ethanol or acetic acid injections.
The researchers conclude that among adults with small liver cancers, radiofrequency ablation results in better survival and fewer recurrences than ethanol or acetic acid injections, but it also results in more complications.
Patients with liver cancer may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating novel therapeutic approaches.
Reference: Lin SM, Lin CJ, Hsu CW et al. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut. 2005;54:1151-1156.