This policy focuses on surgical excision, cryosurgical ablation, radiofrequency ablation and percutaneous ethanol injection as ablative techniques to treat primary or metastatic cancer of the liver.

Note: For related topics please see the following:

• SURG.00025 Cryosurgical Ablation of Solid Tumors;
• SURG.00050 Radiofrequency Ablation to Treat Tumors Outside the Liver;
• RAD.00011 Transcatheter Arterial Chemoembolization (TACE);
• RAD.00033 Selective Internal Radiation Therapy (SIRT) of Primary or Metastatic Liver Tumors (i.e., SIR-Sphere and TheraSpheres)respectively.

Medically Necessary:

Surgical Excision

Surgical excision of liver metastases from colorectal cancer or functioning neuroendocrine tumors are considered medically necessary when the tumor involves no more than one lobe of the liver AND extrahepatic disease has been or will be definitively resected.

Other ablative techniques, i.e., percutaneous ethanol injection, radiofrequency ablation or cryosurgical ablation:

• the patient must be a poor candidate for surgical resection or unwilling to undergo surgical resection; and
• the presence of 3 lesions or less, as documented by MRI; and
• each lesion measures no more than 5 cm in diameter; and
• no evidence of extra-hepatic disease; and
• all foci of disease are amenable to ablative therapy

Investigational/Not Medically Necessary:

Surgical Excision

Surgical excision of metastatic lesions of the liver from tumor primaries other than colorectal or neuroendocrine cancer is considered investigational/not medically necessary.

Ablative Therapies

Ablation by radiofrequency ablation, cryosurgical ablation or percutaneous ethanol injection of metastatic lesions of the liver from tumor primaries other than colorectal or neuroendocrine cancer is considered investigational/not medically necessary.

Surgical excision of other liver tumors not meeting the above criteria is considered investigational/not medically necessary.

Rationale

Surgical resection of isolated primary and metastatic tumors continue to be the gold standard for curative intent of colorectal, neuroendocrine and hepatocellular carcinoma (Berber, 2005; Bleicher, 2003; Fong, 1999; Lermite, 2005, Solmi, 2006). However, alternate ablative techniques are considered when surgical excision is not feasible due to tumor location, size or residual liver function. Among the other treatment options, there is the greatest data regarding radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). For example, Lencioni and colleagues (2003) published a randomized comparison of RFA and PEI in 102 patients with hepatocellular cancer. Tumors were fully ablated in 91% of RFA treated patients and 85% of PEI treated patients; however an average of 5.4 sessions were required for PEI versus 1.1 for RFA. However, there was a significant difference in the local recurrence-free survival rate at one year of 83% and 62% at two years for the PEI group. In comparison, the RFA group had a local recurrence-free survival rate at one year of 96% and 95% at two years. The overall 2 year survival was similar in both groups. Additional non randomized comparative studies reporting survival data also support the equivalency of these two options. (Ikeda, 2001; Livraghi, 1999).

Treatment of neuroendocrine cancers is primarily palliative in nature, to reduce levels of functioning hormones, which may result in significant morbidity. One study reported that radiofrequency ablation resulted in successful treatment of 63% of patients with functioning neuroendocrine tumors (Henn, 2003). While there is considerable published literature regarding cryosurgery, the majority consists of uncontrolled case series that did not report survival data, or papers describing technical aspects of this technique. However one study did provide a comparison between cryosurgery and RFA in patients with either primary hepatocellular cancer or isolated colorectal metastases (Adam, 2002). Survival at one year did not differ in the two groups. While RFA appears to be the most common modality used in this country, the choice of ablative technique is often based on individual physician and institution experience and preference.

In 1999, Fong and colleagues proposed a clinical risk score (CRS) as a tool to predict recurrence rates after hepatic resection for metastatic colorectal carcinoma. The CRS tool included multiple liver metastases, size of tumor > 5cm, bilobar liver disease and extrahepatic disease as factors that predicted negative outcomes. Other studies continue to report on the effects of tumor size and quantity and the impact on the results. Results from PEI on necrosis rates in hepatocellular carcinoma (HCC) had a correlation to the tumor size. HCC smaller than 2cm resulted in 90%-100% necrosis rates, while tumors between 2cm to 3 cm had a 70% necrosis rate and tumors between 3cm to 5cm resulted in 50% necrosis (Bruix, 2005). Lermite and colleagues (2006) reported the significant risk factor that resulted in local recurrence was tumor size >3cm. In a study by Luo (2005) a lower complete necrosis rate of 23% was reported a group with tumors larger than 3cm versus 92.2% in a group with tumors ranging from 1-3cm. Overall survival was also significant between the groups with an advantage in patients with smaller tumors <3cm with a 5 year survival of 33.3% compared to 0.4% in the group with tumors larger than 3cm.

Ablation of larger tumors were more technically challenging as overlapping fields were required to ensure adequate ablation. Radiographic studies present challenges when used to accurately determine the defining margins for overlap. This has been postulated to have been an issue when earlier probes were capable of ablating a maximum of 3cm (Bleicher, 2003; Muilier, 2005). However, newer probes, electrodes and energy generators are being used in clinical practice. As newer technologic devices are developed to treat larger liver lesions, results from randomized studies of ablative therapies (i.e., RFA, PEI, and cryosurgery) for treating more than 3 liver lesions or tumors larger than 5 cm are needed to determine safety and effectiveness.

A 2005 report by the American College of Surgeons stated that a small subset of patients with breast cancer metastases to the liver may be candidates for surgical treatment. The patients likely to benefit will have liver only disease that has been responsive to systemic chemotherapy. Treatment may be performed with curative or palliative intent. Bleicher and colleagues (2003) reported on the use of RFA in a variety of metastatic liver tumors from other primaries, including breast cancer. However the number of tumors other than HCC and colorectal cancer participants was small. Large, randomized studies with long term follow up need to be completed to determine the safety and efficacy of ablative therapies for liver metastases from tumors other than neuroendocrine and colorectal cancer. 

Background/Overview

Hepatic tumors can arise either as primary liver cancer or by metastasis to the liver from other tissues. Local therapy for hepatic metastasis is indicated only when there is no extrahepatic disease, which rarely occurs for patients with primary cancers other than colorectal carcinoma or certain neuroendocrine malignancies. Currently, surgical resection with adequate margins or liver transplantation are considered the treatments of choice. However, many patients are not candidates for surgical resection due to the location or number of lesions, inadequate liver reserve or comorbid conditions. A variety of ablative techniques, i.e., cryosurgical or radiofrequency ablation or percutaneous ethanol injection, have been investigated as options for these patients.

Neuroendocrine tumors may also involve the liver, where hormone production can cause systemic symptoms. The most common neuroendocrine tumor is the carcinoid tumor where excessive hormone production is associated with the carcinoid syndrome, characterized by debilitating flushing, wheezing and diarrhea. Pancreatic endocrine tumors that produce gastrin, insulin or other pancreatic hormones are unusual types of neuroendocrine tumors.  Pancreatic endocrine (i.e., islet cell) tumors must be distinguished from the more common pancreatic epithelial tumors that arise from the exocrine portion of the pancreas. Surgical resection is typically not possible for neuroendocrine tumors, and treatment may be focused on palliation of specific systemic symptoms.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in adults (American Cancer Society, 2006). The disease is almost twice as common in men versus women. HCC is the fifth most common tumor worldwide. HCC is most commonly seen in countries such as Southeast Asia and Africa, where hepatitis endemic.

Cryosurgery, also called cryotherapy or cryosurgical ablation, is the use of extreme cold produced by liquid nitrogen (or argon gas) to destroy abnormal tissue. Cryosurgical ablation is performed by inserting a hollow instrument called a cryoprobe into the lesion followed by circulation of coolant such as liquid nitrogen or argon gas through the hollow probe. The physician utilizes imaging procedures such as ultrasound or MRI to guide the cryoprobe to the tumor location and monitor the freezing process. The monitoring process is important so freezing of the cells is limited to the tumor and its immediate area, limiting the amount of damage to nearby healthy tissue. During a cryosurgical procedure, a ball of ice crystals forms around the probe, freezing nearby cells and killing them. The dead tissue is then naturally absorbed by the body. Sometimes more than one probe is used to deliver the liquid nitrogen to various parts of the tumor. Cryosurgical ablation is performed primarily as an open surgical technique; laparoscopic and percutaneous cryoablation have been described but are used infrequently. Cryosurgical ablation may also be performed in conjunction with surgical resection of other lesions or hepatic artery infusion.

Cryosurgery does have side effects; however, they may be less severe than those associated with conventional surgery or radiation therapy. The effects depend on the location of the tumor but may include bleeding, and in the case of treatment for prostate cancer, incontinence and urinary retention. In rare cases, cryosurgery may interact adversely with certain types of chemotherapy.

Radiofrequency ablation involves inserting an electrode into the center of the tumor with the delivery of alternating current with the intent to destroy tumor cells Protein denaturation and coagulation is the ultimate cause of cell death. Radiofrequency ablation may be performed percutaneously, laparoscopically or in an open procedure. The procedure kills cells (cancerous and normal) by applying a heat-generating rapidly alternating current through probes inserted into the tumor. The effective volume of RFA depends on the frequency and duration of applied current, local tissue characteristics, and probe configuration (e.g., single versus multiple tips). RFA can be performed as an open surgical procedure, laparoscopically, or percutaneously with ultrasound or computed tomography (CT) guidance.

Percutaneous ethanol injection describes the injection of ethanol directly into tumor tissue, where it destroys the tumor tissue due to its dehydrative and protein degenerative effects. Furthermore, the relative hypervascularity of HCC ensures good penetration of the tumor with minimal spillover of ethanol into normal liver tissue. This treatment has been used more extensively in Italy and Japan where cirrhosis and hepatocellular cancer are endemic. In these countries, screening techniques, such as ultrasound and measurement of alpha-feto protein levels are able to detect small asymptomatic hepatocellular cancers arising in the cirrhotic livers.

Common complications of ablative therapies include abscess formation, infection, hemorrhage and injury to adjacent anatomical organs. There have also been reports of mortalities associated with the ablative procedures.  

Definitions

Ablation: the destruction of a body part or tissue or its function; may be achieved by surgery, hormones, drugs, radiofrequency, heat, or other methods

Extra-hepatic metastases: cancer that has spread from its original location to the liver

Hepatic metastases: cancer that has spread from its original location to the liver

Metastasis: the spread of cancer from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread

Neuroendocrine tumor: tumors arising from cells that produce hormones that can cause systemic symptoms such as flushing or wheezing; examples of neuroendocrine tumors include, but are not limited to carcinoid tumors, islet cell tumors, medullary thyroid carcinoma, and pheochromocytoma

Primary hepatocellular cancer: a cancer that originates within liver cells

Unresectable: refers to a tumor that cannot safely be removed surgically due to size or location

Coding

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Surgical Excision
When services are Medically Necessary:

CPT

ICD-9 Procedure

ICD-9 Diagnosis

When services may be Medically Necessary, when criteria are met:
For the procedure codes listed above, for the following diagnoses

ICD-9 Diagnosis

When services are Investigational/Not Medically Necessary:
For the procedure codes listed above, for metastatic liver tumors from other primary sites not listed, or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

Ablative Techniques
When services may be Medically Necessary when criteria are met:

CPT

ICD-9 Procedure

ICD-9 Diagnosis

When services are Investigational/Not Medically Necessary:
For the procedure codes listed above, when criteria are not met and for all other diagnoses not listed; or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

References

Peer Reviewed Publications:

1. Adam R, Hagopian EJ, Linhares M, et al. A comparison of percutaneous cryosurgery and percutaneous radiofrequency for unresectable hepatic malignancies. Arch Surg. 2002; 1 37:1332-1339.
2. Berber E, Felsher N, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastasis. World J Surg. 2002; 26:985-990.
3. Berber E, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases. Problems in General Surgery. 2003; 20(3): 134-142.
4. Berber E, Pelley R, Siperstein AE. Predictors of survival after radiofrequency thermal ablation of colorectal cancer metastases to the liver: a prospective study. J Clin Oncol. 2005; 23(7): 1358-1364.
5. Bleicher RF, Allegra DP, Nora DT, et al. Radiofrequency ablation in 447 complex unresectable liver tumors: lessons learned. Annals of Surgical Oncology. 2003; 10(1):52-58.
6. Bruix J, Sherman M. American Association for the Study of Liver Disease (AASLD) Practice Guideline: Management of hepatocellular carcinoma. Hepatology. 2005; 42(5): 1208-1235. Available at: https://www.aasld.org/eweb/docs/practiceguidelines/Hepatocellularcarcinoma.pdf. Accessed on April 20, 2007.
7. Henn AR, Levine EA, McNulty W, et al. Percutaneous radiofrequency ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol. 2003; 181:1005-1010.
8. Ikeda M, Okada S, Ueno H, et al. Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: A comparative study. Jpn J Clin Oncol. 2001; 31:322-326.
9. Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003; 228:235-240.
10. Lermite E, Lebigot J, Oberti F, et al. Radiofrequency thermal ablation of liver carcinoma. Prospective study of 82 lesions. Gastroenterol Clin Biol. 2006; 30:130-135.
11. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: Treatment with radiofrequency ablation versus ethanol injection. Radiology. 1999; 210:655-661.
12. Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000; 214:761-768.
13. Lu DSK, Yu NC, Raman SS, et al. Radiofrequency Ablation of Hepatocellular Carcinoma: Treatment Success as Defined by Histologic Examination of the Explanted Liver. Radiology. 2005; 234:954-960. 
14. Mulier S, Ni Y, Jamart J, Ruers T, et al. Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg. 2005; 242(2):158-171.
15. Siperstein AE, Berber E. Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg. 2001; 25:693-696.
16. Solmi L, Nigro G, Roda E. Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle elect rode in hepatocellular carcinoma. World J Gastroenterol. 2006; 12(7):1098-1104.
17. Stippel DL, Brochhagen HG, Arenja M, et al. Variability of size and shape of necrosis induced by radiofrequency ablation in human livers: a volumetric evaluation. Ann Surg Oncol. 2004; 11(4):420-425.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Cancer Society (ACS). Overview Liver Cancer. Revised April 11, 2006. Available at:
   http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_liver_cancer_treated_25.asp. Accessed on April 11, 2007.
2. American College of Surgeons. Surgical Treatment of Breast Cancer Liver Metastases. April 2005. Available at: http://www.facs.org/spring_meeting/2005/gs14curley.pdf. Accessed on April 17, 2006.
3. Hayes Inc. Hayes Medical Technology Directory. Radiofrequency Ablation for Primary and Metastatic Cancers of the Liver. Lansdale, PA; Hayes, Inc.; April 2004. Search updated October 11, 2006.
4. Hayes Inc. Hayes Medical Technology Directory. Cryosurgery for Primary and Metastatic Liver Tumors. Lansdale, PA: Hayes, Inc.; October 2004. Search updated November 19, 2006.
5. National Comprehensive Cancer Network® (NCCN) V.1.2007. Hepatobiliary Cancer. January 23, 2007. Available at: http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. Accessed on April 18, 2007.
   

Web Sites for Additional Information

1. American Cancer Society. Available at: www.cancer.org. Accessed on April 11, 2007.
2. National Cancer Institute. Adult Primary Liver Cancer (PDQ®): Treatment. Last modified February 26, 2007. Available at: http://www.nci.nih.gov/cancerinfo/pdq/adulttreatment. Accessed on April 17, 2007.
3. National Cancer Institute. Colon Cancer (PDQ®): Treatment. Last modified May 20, 2005. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/colon/patient. Accessed on April 17, 2007.

Index

Policy History

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

©CPT Only - American Medical Association