![]() | Medical Policy |
| Subject: | Locally Ablative Techniques for Treating Primary and Metastatic Liver Malignancies | ||
| Policy #: | SURG.00065 | Current Effective Date: | 07/15/2009 |
| Status: | Revised (Coding updated 10/01/2009) | Last Review Date: | 05/21/2009 |
| Description/Scope |
This document focuses on surgical excision, cryosurgical ablation, microwave 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:
| Position Statement |
Medically Necessary:
Investigational and Not Medically Necessary:
Surgical Excision
Surgical excision of liver tumors not meeting the above criteria is considered investigational and not medically necessary.
Ablative Therapies
Ablation by radiofrequency ablation, cryosurgical ablation, microwave ablation, or percutaneous ethanol injection of metastatic lesions of the liver from tumor primaries other than colorectal or neuroendocrine cancer is considered investigational and not medically necessary.
Ablation by radiofrequency ablation, cryosurgical ablation, microwave ablation, or percutaneous ethanol injection of metastatic lesions of the liver not meeting the above criteria is considered investigational and not medically necessary.
| Rationale |
Surgical Excision
Surgical resection of isolated primary and metastatic tumors continues 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 may be 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).
In a consensus statement on selecting patients for resection of hepatic colorectal metastases (Charnsangavej, 2006), the authors concluded patients with primary colorectal tumors presenting with synchronous resectable liver metastases should be considered for aggressive curative-intent therapy when appropriate. The authors noted a "paradigm shift" in the definition of resectability noting 20% of the total liver volume "appears to be the minimum safe volume that can be left following extended resection in patients with normal underlying liver." Extrahepatic disease is considered a relative contraindication that requires careful patient selection when considering liver resection.
Adam and colleagues (2006) reported the results of a retrospective study of 1452 patients with noncolorectal nonendocrine liver metastases (NCNELM), all of whom received hepatic resection. 32% breast, 16% gastrointestinal and 14% urologic sites were the most frequent primary sources for the liver metastases. The overall 5-year and 10-year survival rates for all patients were 36% and 23%, respectively. The median overall survival was 35 months. The median recurrence free survival was 11 months, and 5- and 10-year recurrence free survival of 14% and 10%, respectively. Major complications occurred at a rate of 21.5% with a 60-day mortality rate of 2.3%. Although the study data appeared to be encouraging, there was no analysis of how many other patients with such metastases were refused or otherwise did not receive surgery, nor of the criteria used in making the decision to operate. Thus, while such a descriptive study showed that longer-term survival may be possible in some patients and the authors assessed multivariate factors affecting survival, there was no comparison of variables between the surgical group and those with similar disease who never received surgery.
Locally ablative techniques for hepatocellular carcinoma, liver metastases from colorectal carcinoma or neuroendocrine tumors:
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).
In a study of 153 enrolled patients with newly diagnosed hepatocellular carcinoma (HCC) patients, Morimoto and colleagues (2007) described two cohorts of patients with single HCC tumors (102) and two or three (51) HCC nodules of 5 cm or less in maximum diameter. 110 patients received RFA ablation while 43 patients received PEI. The overall survival at 3 years was 75% and 59% at 5 years. 125 (82%) of patients had no local tumor at 6 months after initial treatment. 28 (18%) of patients had residual tumor and were retreated. There was no significant difference in successful treatment outcome between the treatment modalities. Of the 110 patients treated with RFA, 90 (82%) and 35 (81%) of patients had no residual tumor by contrast enhanced computerized tomography (CT) at 6 months. Median follow-up of 34 months revealed 58 (53%) of 110 patients treated with RFA and 25 (58%) of 43 patients treated with PEI had tumor recurrence. 23 patients died and 3 patients were lost to follow-up. Tumor size was one of the pre-treatment factors associated with survival. Overall, the significant predictor of survival was the response to initial treatment.
Taniguchi and colleagues (2008) reported long-term study results of 31 patients with HCC lesions < 15 mm treated with PEI. Overall survival rate at 3-, 5-, 7- and 10-years was 74.1%, 49.9%, 27.2% and 14.5%, respectively. A subset analysis noted a significant correlation between hepatic function and survival. Patients with Child-Pugh class A had a higher survival rate compared with Child-Pugh class B (p = 0.011).
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 > 5 cm, 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 2 cm to 3 cm had a 70% necrosis rate and tumors between 3 cm to 5 cm resulted in 50% necrosis (Bruix, 2005). Lermite and colleagues (2006) reported the significant risk factor that resulted in local recurrence was tumor size >3 cm. In a study by Luo (2005) a lower complete necrosis rate of 23% was reported in a group with tumors larger than 3 cm versus 92.2% in a group with tumors ranging from 1-3 cm. Overall survival was also significant between the groups with an advantage in patients with smaller tumors <3 cm with a 5 year survival of 33.3% compared to 0.4% in the group with tumors larger than 3 cm.
Ablation of larger tumors was 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 3 cm (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, microwave ablation, or cryosurgery) for treating more than 3 liver lesions or tumors larger than 5 cm are needed to determine safety and effectiveness.
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).
Locally ablative techniques for metastases from other solid tumors:
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. There are multiple small case series reporting on resection or ablative therapies for metastatic liver tumors from other primary sites. However, the cohorts are small and lacking long term follow-up 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.
Cryosurgical ablation:
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.
Microwave ablation
Zhang and colleagues (2008) reported on a retrospective study of 160 patients treated with microwave ablation of liver tumors. Specific diagnoses included primary hepatic cancer (i.e., hepatoma/hepatocellular carcinoma [HCC]) in 97 patients, and metastatic cancer to the liver from other primary sites in 63 patients. A mean number of 2.2 microwave applications were performed per patient. A second microwave treatment for recurrent disease was performed on eight patients, and two patients required a third treatment. 86 patients were followed for more than one year and 96% of patients treated for primary liver cancer were alive after one year versus 82.1% of patients treated for metastases (p = 0.022). One-year overall survival was 91.8%. Alfa-fetoprotein (AFP) levels in 25 patients with primary liver cancer decreased from 104.2 ± 22.5 ng/ml to 24.6 ± 3.6 ng/ml (p < 0.05) after microwave ablation. There were no operative deaths, and complications were medically managed. Fever was noted in 76.3% of patients, and was managed with indomethacin. Increased transaminases occurred in 80% (128/160) patients, and resolved within a day or two without special treatment in patients without pre-existing ascites. Pleural effusions were noted in 14 patients with only one patient requiring a chest tube for drainage. The authors concluded microwave ablation therapy was safe and effective for liver tumors. In addition, specialty consensus opinion suggests microwave ablation therapy may be used for primary and secondary liver carcinomas.
| Background/Overview |
Primary hepatobiliary carcinoma pertains to malignancies arising from the liver, bile ducts and/or gallbladder. Hepatic carcinoma can arise either as primary liver cancer or by metastasis to the liver from other tissue origins. Malignancies of the liver are comprised primarily of adenocarcinomas classified by hepatocellular and cholangiocarcinoma cell types (National Cancer Institute [NCI], 2009). Hepatocellular carcinoma is the most common form of hepatic malignancies (National Comprehensive Cancer Network [NCCN®], 2009). Gallbladder cancer is the most common type of biliary tract malignancies (NCCN, 2009). Cholangiocarcinoma occurs throughout the biliary tree (NCCN, 2009).
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.
Local ablative 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, has been investigated as options for these patients.
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. 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
Cholangiocarcinoma: a type of cancer developing in cells that line the bile ducts in the liver
Extra-hepatic disease: cancer that is located outside of 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 (the origin of the cancer) to another part of the body; 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 document 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 may be Medically Necessary when criteria are met:
| CPT | |
| 47120 | Hepatectomy, resection of liver; partial lobectomy |
| 47122 | Hepatectomy, resection of liver; trisegmentectomy |
| 47125 | Hepatectomy, resection of liver; total left lobectomy |
| 47130 | Hepatectomy, resection of liver; total right lobectomy |
| ICD-9 Procedure | |
| 50.22 | Partial hepatectomy |
| 50.3 | Lobectomy of liver |
| ICD-9 Diagnosis | |
| 140.0-199.2 | Malignant neoplasms |
| 209.00-209.36 | Malignant carcinoid tumor |
| 209.70-209.79 | Secondary neuroendocrine tumors |
| 230.8 | Carcinoma in situ of liver and biliary system |
| 259.2 | Carcinoid syndrome |
When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
Ablative Techniques
When services may be Medically Necessary when criteria are met:
| CPT | |
| 47370 | Laparoscopy, surgical, ablation of one or more liver tumor(s); radiofrequency |
| 47371 | Laparoscopy, surgical, ablation of one or more liver tumor(s); cryosurgical |
| 47380 | Ablation, open, of one or more liver tumor(s); radiofrequency |
| 47381 | Ablation, open, of one or more liver tumor(s); cryosurgical |
| 47382 | Ablation, one or more liver tumor(s), percutaneous, radiofrequency |
| 76940 | Ultrasound guidance for, and monitoring of, parenchymal tissue ablation |
| 77013 | Computed tomography guidance for, and monitoring of, parenchymal tissue ablation |
| 77022 | Magnetic resonance guidance for, and monitoring of, parenchymal tissue ablation |
| No specific code for microwave ablation or percutaneous ethanol injection | |
| ICD-9 Procedure | |
| 50.29 | Other destruction of lesion of liver |
| ICD-9 Diagnosis | |
| 153.0-153.9 | Malignant neoplasm of colon |
| 154.0-154.8 | Malignant neoplasm of rectum, rectosigmoid junction, and anus |
| 155.0-155.2 | Malignant neoplasm of the liver |
| 157.4 | Malignant neoplasm of Islets of Langerhans |
| 193 | Malignant neoplasm of thyroid gland |
| 194.0-194.9 | Malignant neoplasm of other endocrine glands and related structures |
| 197.7 | Secondary malignant neoplasm of liver |
| 209.00-209.36 | Malignant carcinoid tumors |
| 209.70-209.79 | Secondary neuroendocrine tumors |
| 230.8 | Carcinoma in situ of liver and biliary system |
| 259.2 | Carcinoid syndrome |
When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
| References |
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
| Web Sites for Additional Information |
| Index |
Cryoablation
Hepatic Tumors
Liver Tumors
Microwave Ablation
Percutaneous Ethanol Injection (PEI)
Radiofrequency Ablation (RFA)
Surgical Ablation
| History |
| Status | Date | Action |
| 10/01/2009 | Updated coding section with 10/01/2009 ICD-9 changes. | |
| Revised | 05/21/2009 | Medical Policy & Technology Assessment (MPTAC) review. |
| Revised | 05/20/2009 | Hematology/Oncology Subcommittee review. Fixed formatting in criteria. Added microwave ablation as an example of locally ablative technique. Removed examples of treatment modalities from the title. Updated rationale, references and coding. |
| Revised | 11/20/2008 | MPTAC review. |
| Revised | 11/19/2008 | Hematology/Oncology Subcommittee review. Revised surgical excision of primary hepatobiliary carcinoma or liver metastases from colorectal cancer and functioning neuroendocrine tumors. Added medically necessary criteria for surgical excision of liver metastases from other solid tumors. Updated references, rationale and coding section. |
| 10/01/2008 | Updated coding section with 10/01/2008 ICD-9 changes. | |
| Reviewed | 05/15/2008 | MPTAC review. |
| Reviewed | 05/14/2008 | Hematology/Oncology Subcommittee review. |
| Revised | 11/29/2007 | MPTAC review. |
| Revised | 11/28/2007 | Hematology/Oncology Subcommittee review. Clarified medical necessity statements to include hepatocellular carcinoma. Added CT scan to radiographic criteria. Added investigational and not medically necessary statements for indications when criteria are not met. The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary." |
| Reviewed | 05/17/2007 | MPTAC review. |
| Reviewed | 05/16/2007 | Hematology/Oncology Subcommittee review. Reviewed literature on tumor size and number of tumors without change to criteria. Updated references, background and coding. |
| 01/01/2007 | Updated coding section with 01/01/2007 CPT/HCPCS changes; removed CPT 76362, 76394 deleted 12/31/2006. | |
| Revised | 06/08/2006 | MPTAC review. Updated references and coding. |
| Revised | 06/07/2006 | Hematology/Oncology Subcommittee review. Updated references and coding. |
| Revised | 07/14/2005 | MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization. |
| Pre-Merger Organizations | Last Review Date | Document Number | Title |
| Anthem, Inc. | 04/28/2005 | SURG.00025 | Cryosurgical Ablation of Solid Tumors |
07/27/2004 | SURG.00050 | Radiofrequency Ablation of Solid Tumors | |
| WellPoint Health Networks, Inc. | 06/24/2004 | 3.06.03 | Locally Ablative Techniques for Treating Primary and Metastatic Liver Cryosurgical Ablation, Radiofrequency Ablation or Percutaneous Ethanol Injection) |