Transarterial Chemoembolization (TACE) of the Liver

Medical Policy: 02.02.08 
Original Effective Date: July 2001 
Reviewed: November 2011 
Revised: October 2010 

Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description: 

Transarterial chemoembolization (TACE) of the liver is a treatment modality often used as an alternative to conventional systemic or intra-arterial chemotherapy, or in instances where conventional treatment has failed. TACE is intended to induce tumor necrosis through administration of chemotherapy and an embolizing agent directly into the tumor by way of the feeding artery. TACE combines the infusion of chemotherapeutic drugs with particle embolization. Tumor ischemia secondary to the embolization raises the drug concentration compared to infusion alone, extending the retention of the chemotherapeutic agent and decreasing systemic toxicity. The liver is especially amenable to this approach, given its distinct lobular anatomy, the existence of 2 independent blood supplies, and the ability of healthy hepatic tissue to grow and thus compensate for tissue mass lost during chemoembolization.

TACE of the liver has been associated with potentially life-threatening toxicities and complications, including severe postembolization syndrome, hepatic insufficiency, abcess, or infarction. TACE has been investigated to treat resectable, unresectable, and recurrent hepatocellular carcinoma, to treat liver metastases, and in the liver transplant setting. Treatment alternatives include resection when possible, chemotherapy administered systemically or by hepatic artery infusion (HAI). HAI involves continuous infusion of chemotherapy with an implanted pump, while TACE is administered episodically.

The TACE procedure requires hospitalization for placement of the hepatic artery catheter and workup to establish eligibility for chemoembolization. Prior to the procedure, the patency of the portal vein must be demonstrated to ensure an adequate post-treatment blood supply. The catheter is inserted via the femoral artery and threaded into the hepatic artery. Angiography is preformed to delineate hepatic vasculature, followed by injection of the embolic chemotherapy mixture. Embolic material varies, but may include a viscous collagen agent, polyvinyl alcohol particles, or ethiodized oil. Typically, 1 lobe of the liver is treated during a single session, with subsequent embolization procedures scheduled from 5 days to 6 weeks later. In addition, since the embolized vessel recanalizes, chemoembolization can be repeated as many times as necessary.

Recent studies have assessed TACE with drug-eluting beads (DEB-TACE) in patients with unresectable hepatocellular carcinoma. A unique drug delivery embolization system, drug-eluting beads have been pre-loaded with a chemotherapeutic agent. In preclinical and clinical studies, drug-eluting beads have demonstrated the ability to achieve higher tumor concentrations and lower systemic concentrations of the chemotherapeutic agent compared to intra-arterial chemotherapy and conventional TACE. Some early studies have suggested survival advantage, fewer recurrences and improved tumor response associated with drug-eluting beads. However, other studies have demonstrated comparable effectiveness when compared to conventional TACE, although significant reductions in toxicity. In addition to studies comparing DEB-TACE with conventional TACE, additional studies have compared drug-eluting beads loaded with irinotecan (DEBIRI) with DEBs loaded with doxorubicin.  Large prospective studies are needed to confirm these early study findings and standardize this treatment.

Top

Prior Approval: 

Not applicable

Top

Policy: 

Transarterial chemoembolization of the liver may be considered medically necessary for the following indications:

• To treat hepatocellular cancer that is unresectable but confined to the liver and not associated with portal vein thrombosis
• To treat liver metastasis in symptomatic patients with metastatic neuroendocrine tumors whose symptoms persist systemic therapy and who are not candidates for surgical resection
• To treat liver metastasis inpatients with liver-dominant metastatic uveal melanoma
• As a bridge to transplant in patients with hepatocellular cancer where the intent is t prevent further tumor growth and to maintain a patient's candidacy for liver transplant

Transarterial chemoembolization of the liver is considered investigational as a treatment of liver metastases from other non-neuroendocrine primaries, including colorectal cancer, melanoma, and unknown primaries. Studies have consisted of small numbers of patients, and the results have been variable across studies due to variation in patient selection criteria and regimens used between different studies.

Transarterial chemoembolization of the liver is considered investigational to treat hepatocellular tumors prior to liver transplant except as noted above.

Transarterial chemoembolization of the liver is considered investigational as neoadjuvant or adjuvant therapy in resectable hepatocellular cancer. There are little data on the use of TACE in the neoadjuvant or adjuvant setting, and a significant long-term survival benefit has not been demonstrated.

Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered investigational.

Top

Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9 diagnostic codes.
• 37204 Transcatheter occlusion or embolization (e.g., for tumor destruction, to achieve homeostasis, to occlude a vascular malformation), percutaneous, any method, non-central nervous system, non-head or neck
• 75894 Transcatheter therapy, embolization, any method, radiological supervision and interpretation. 

Top

Selected References: 

• Wallace S, Kan Z, Li C. Hepatic chemoembolization : Clinical and experimental correlation. ACTA Gastroenterologica Belgica 2000 April-Jun;63(2):169-173.
• Al-Bassam SH, Munk PL, Sallomi DF, Morris DC, Lee MJ, Chung SW, Connell, DG. Chemoembolization of hepatic tumors. Australasian Radiology 1999 May; 43 (2):165-174. 
• Ramsey D, Kernagis LT, Soulen MC, Geschwind JF Chemoembolization of hepatocellular carcinoma. Journal of Vascular and Interventional Radiology; September 2002; 13 (9 Suppl): s211-21.
• Sumie S, Yamashita F, Ando E, et al. Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization. AJR Am J Roentgenol. 2003 Nov; 181(5): 1327-34.
• Guo WJ, Yu EX, Lui LM, et al. Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma. World J Gastroenterol 2003; 9(8): 1697-1701.
• Sun HC, Tang ZY. Preventive treatments for recurrence after curative resection of hepatocellular carcinoma- A literature review of randomized control trials. World J Gastroenterol 2003; 9(4): 635-640.
• Yang YY, Lin HC, Hou MC, et al. Good response to hepatic arterial chemoembolization in a patient with primary neuroendocrine tumor of the liver. J Chin Med Assoc. 2003 Apr; 66(4): 247-51.
• Guo WE, Yu EX. The long-term efficacy of combined chemoembolization and local irradiation in the treatment of patients with large hepatocellular carcinoma.
• Wu F, Wang ZB, Chen WZ et al. Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology. 2005 May; 235(2):659-6.
• Jang MK, Lee HC, Kim IS et al. Role of additional angiography and chemoembolization in patients who achieved complete necrosis following transarterial chemoembolization. J Gastroenterol Hepatol. 2004 Sep;19(9):1074-80.
• Agarwala SS, Panikkar R, Kirkwood JM, Phase I/II randomized trial of intrahepatic arteial infusion chemotherapy with cisplatin and chemoembolization and polyvinyl sponge in patients with ocular melanoma metastic to the liver. Melanoma Res. 2004 Jun; 14(3):217-22.
• Fiorentini G, Rossi, S, Bonechi F et al. Intra-arterial hepatic chemoembolization in liver metastases from neuroendocring tumors: a phase II study. J Chemother. 2004 Jun; 16(3):293-7.
• Blue Cross and Blue Shield Association. Medical Policy No. 8.01.11; Transcatheter Arterial Chemoembolization to treat Primary or Metastatic Liver Malignancies. 2005.
• Bisselli M, Andreone P, Gramenzi A et al. Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study. Clin Gastroenterol Hepatol. 2005; 3(9):918-25.
• Cheng HY, Wang X, Chen D et al. The value and limitation of transcatheter arteial chemoembolization in preventing recurrence of resected hepatocellular carcinoma. World J Gastroenterol. 2005; 11(23):3644-6.
• Molinari M, Kachura JR, Dixon E et al. Transarterial chemoembolization for advanced hepatocellular carcinoma: results from a North American cancer centre. Clin Oncol (R Coll Radiol) 2006; 18(9):684-92.
• Takayasu K, Arii S, Ikai I et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006; 131(2):461-9.
• Ruutiaienen AT, Soulen MC, Tuite CM et al. Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol 2007; 18(7):847-55.
• Kim JH, Yoon HK, Kim SY et al. Transcatheter arterial chemoembolization versus chemoinfusion for unresectable hepatocellular carcinoma in patients with major portal vein thrombosis. Aliment Pharmacol Ther. 2009 Apr 8. [Epub ahead of print].
• Eguchi S, Hidaka M, Tomonaga T, Miyazaki K et al. Actual therapeutic efficacy of pre-transplant treatment on hepatocellular carcinoma and its impact on survival after salvage living donor liver transplantation. J Gastroenterol. 2009 Apr 21. [Epub ahead of print].
• Sacco R, Bertini M, Petruzzi P et al. Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study. World J gastroenterol. 2009 Apr 21; 15(15):1843-8.
• Chua TC, Liauw W, Saxena A et al. Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma. Liver Int. 2010 Feb 30(2); 166-74.
• Chua TC, Saxena A, Liauw W et al. Systematic review of randomized and nonrandomized trials of clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol. 2010 Feb;17(2): 492-501. Epub 2009 Oct 24.
• Zhou WP, Lai EC, Li AJ et al. A prospective, randomized, controlled trial of preoperative transarterial chemoembolization for resectable large hepatocellular carcinoma. Ann Surg 2009; 249(2): 195-202.
• Nazario J, Gupta S. Transarterial liver-directed therapies of neuroendocrine hepatic metastases. Semin Oncol 2010; 37(2): 118-26.
• Dhanasekaran R, Kooby DA, Staley CA et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug-eluting beads (DEB) for unresectable hepatocellular carcinoma (HCC). J Surg Oncol. 2010 May 1; 101(6):476-80.
• Reyes DK, Vossen JA, Kamel IR et al. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 2009 Nov-Dec; 15(6):526-32.
• Malagari K, Pomoni M, Kelekis A et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010 Jun;33(3):541-51. Epub 2009 Nov 24.
• Lammer J, Malagari K, Vogl T et al. Prospective randomized study of doxorubicin-eluting bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2009 Nov 12 [Epub ahead of print].
• Vogl TJ, Lammer J, Lencioni R et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011 Oct;197(4):W562-70.
• Martin RC, Howard J, Tomalty D et al. Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry. Cardiovasc Intervent Radiol. 2010; 33(5):960-66.

Top

Policy History: 

Date                                        Reason                               Action

October 2010                         Annual review                     Policy revised

November 2011                     Annual review                     Policy renewed

Top

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.