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Locoregional Therapies for Hepatocellular Carcinoma and Metastatic Liver Carcinoma and Metastatic Carcinoid Tumors of the Liver

Policy Number: MP-070

Latest Review Date: July 2021

Category: Surgical                                                                 

Policy Grade:  B

POLICY:

Radio-frequency Ablation (RFA) may be considered medically necessary for patients with one of the following indications:

  • hepatocellular carcinoma (HCC)
  • metastatic liver carcinoma

Percutaneous Ethanol Injection (PEI) may be considered medically necessary for patients with one of the following indications:

  • hepatocellular carcinoma (HCC)
  • metastatic liver carcinoma

Please refer to Policy #512 ‘Microwave Tumor Ablation’ for coverage information on microwave tumor ablation for the liver, lung, and renal.

Please refer to Policy #178 ‘MRI-Guided Focused Ultrasound (MRgFUS)’ for coverage information on ultrasound ablation of the bone.

Please refer to Policy #119 ‘Radiofrequency Ablation of Solid Tumors Excluding Liver Tumors’ for coverage information on radiofrequency ablation of solid tumors excluding liver

Please refer to Policy #384 ‘Whole Gland Cryoablation of Prostate Cancer’ for coverage information on cryoablation of the Prostate

Please refer to Policy #429 ‘Cryosurgical Ablation of Miscellaneous Solid Tumors Other than Liver, Prostate, or Dermatologic Tumors’ for coverage information on cryosurgical ablation of these tumors.

Please refer to Policy MP# 737 ‘Transcatheter Arterial Chemoembolization to Treat Primary or Metastatic Liver’ for coverage information on Transcatheter Arterial Chemoembolization.

DESCRIPTION OF PROCEDURE OR SERVICE:

Hepatic tumors can arise either as primary liver cancer (hepatocellular cancer) or by metastasis to the liver from other tissues. At present, surgical resection with adequate margins or liver transplantation constitutes the only treatments available with demonstrated curative potential. However, because most hepatic tumors are unresectable at diagnosis, due either to their anatomic location, size, number of lesions, or underlying liver reserve; local therapy may be indicated.

Local therapy for hepatic metastasis is indicated only when there is no extrahepatic disease, which rarely occurs for patients with primary cancers other than CRC or certain neuroendocrine malignancies. For liver metastases from CRC, postsurgical adjuvant chemotherapy has been reported to decrease recurrence rates and prolong time to recurrence. Combined systemic and hepatic arterial chemotherapy may increase disease-free intervals for patients with hepatic metastases from CRC but apparently is not beneficial for those with unresectable hepatocellular carcinoma.

Neuroendocrine tumors are tumors of cells that possess secretory granules and originate from the neuroectoderm. Neuroendocrine cells have roles both in the endocrine system and the nervous system. They produce and secrete a variety of regulatory hormones, or neuropeptides, which include neurotransmitters and growth factors. Overproduction of the specific neuropeptides produced by the cancerous cells causes a variety of symptoms depending on the hormone produced. They are rare, with an incidence of two to four per 100,000 per year.

Treatment options for hepatocellular carcinoma (HCC) range from potentially curative treatments, such as resection or liver transplantation, to nonsurgical options, which include ablative therapies (radiofrequency ablation [RFA], cryoablation, microwave ablation, percutaneous ethanol or acetic acid injection), transarterial embolization, radiation therapy, and systemic therapy. Choice of therapy depends on the severity of the underlying liver disease, size, and distribution of tumors, vascular supply, and patient overall health. Treatment of liver metastases is undertaken to prolong survival and reduce endocrine-related symptoms and hepatic mass-related symptoms.

Various locoregional therapies for unresectable liver tumors have been evaluated: transhepatic arterial embolization (TACE), radiofrequency ablation, percutaneous ethanol injection, microwave ablation, cryosurgical ablation (cryosurgery), and radioembolization with yttrium-90 microspheres.

Radio-frequency Ablation (RFA)

Radiofrequency ablation (RFA) is a procedure in which a probe is inserted into the center of a tumor and heated locally by a high-frequency, alternating current that flows from electrodes. The local heat treats the tissue adjacent to the probe, resulting in a 3 to 5 cm sphere of dead tissue. The cells killed by RFA are not removed but are gradually replaced by fibrosis and scar tissue. If there is a local recurrence, it occurs at the edge of the treated tissue and, in some cases, is retreated. Radiofrequency ablation may be performed percutaneously, laparoscopically, or as an open procedure.

RFA has been investigated as a treatment for unresectable hepatic tumors, both as a primary intervention and as a bridge to liver transplant. In the latter setting, RFA is being tested to determine whether it can reduce the incidence of tumor progression in patients awaiting transplantation and thus maintain patients’ candidacy for liver ablation, transhepatic arterial chemoembolization, microwave coagulation, percutaneous ethanol injection, and radioembolization (yttrium-90 microspheres).

Percutaneous Ethanol Injection (PEI)

PEI induces tumor necrosis by cellular dehydration, protein denaturation, and thrombosis of small vessels. HCC is softer than the surrounding cirrhotic liver and is often encapsulated, allowing selective diffusion of ethanol within the tumor mass. The hypervascularization of HCC also favors ethanol injection therapy by enhancing the distribution of ethanol within the network of the tumor vessels. A fine needle is inserted into the tumor under ultrasonographic guidance, and absolute ethanol is then injected slowly into the tumor until the whole area of tumor appears hypoechogenic on the ultrasound. PEI may be performed under CT guidance for tumors not visualized by ultrasounds. The injection is repeated once or twice a week for up to six to eight sessions, depending on the tumor size. PEI can be done as an outpatient procedure under local anesthesia.

KEY POINTS:

The most recent literature update was performed through June 2, 2021.

Summary of Evidence

RFA

Operable Hepatocellular Carcinoma

For individuals who have primary, operable hepatocellular carcinoma (HCC) who receive RFA, the evidence includes meta-analyses of randomized controlled trials (RCTs) and/or retrospective observational studies and additional observational studies. Relevant outcomes are overall survival (OS), disease-specific survival, change in disease status, and morbid events. The majority of data found that patients undergoing surgical resection experienced longer survival outcomes and lower recurrence rates than patients receiving RFA, though complication rates were higher with surgical resection. Some meta-analyses of specifically selected populations (eg, small tumor sizes or Child-Pugh Class A liver function or HCC within the Milan criteria) found that OS and disease-free survival (DFS) rates were not significantly different between RFA and surgical resection. Results from observational studies have suggested that RFA alone or RFA plus PEI could be as effective as a resection for small HCC tumors as OS and DFS rates were not significantly different between RFA and surgical resection. An exact tumor cutoff size has not been established. Some studies found that OS was similar in patients receiving RFA or resection when tumor size was 3 cm or less; however, OS was significantly longer in patients undergoing resection if the tumor size was between 3.1 cm and 5 cm. Further study in a multicenter RCT would permit greater certainty whether RFA, with or without other ablative or arterial directed therapies, is as effective as surgical resection in treating HCC tumors 3 cm or smaller. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Inoperable Hepatocellular Carcinoma

For individuals who have inoperable, hepatocellular carcinoma (HCC) who receive RFA, the evidence includes RCTs and several systematic reviews and meta-analyses. Relevant outcomes are OS, disease-specific survival, change in disease status, and morbid events. When resection is not an option, nonsurgical options include RFA, PEI, TACE, cryoablation, microwave ablation, and systemic therapy. Meta-analyses comparing RFA to other local ablative therapies have found that RFA and microwave ablation are similarly effective, that RFA is more effective than PEI, and that RFA may be better than cryoablation. The evidence comparing RFA with TACE is limited, and no conclusions can be drawn. RFA has also been shown to improve survival in patients with unresectable HCC as an adjunct to chemotherapy. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Inoperable Hepatic Metastases of Colorectal Origin

For individuals with hepatic metastases of colorectal origin who receive RFA, the evidence includes an RCT, systematic reviews and meta-analyses, prospective cohort series, and retrospective case series. Relevant outcomes are overall survival, disease-specific survival, symptoms, changes in disease status, morbid events, quality of life, and treatment-related morbidity. There are no RCTs comparing RFA with alternative treatments for patients with unresectable colorectal liver metastases. However, an RCT assessing RFA combined with chemotherapy found improved survival at 8 years compared with chemotherapy alone. In addition, prospective studies have demonstrated that overall survival following RFA is at least equivalent and likely better than that obtained with currently accepted systemic chemotherapy in well-matched patients with unresectable hepatic metastatic CRC who do not have extrahepatic disease. Results from a number of uncontrolled case series also suggest RFA of hepatic CRC metastases produces long-term survival that is at minimum equivalent but likely superior to historical outcomes achieved with systemic chemotherapy. Evidence from one comparative study suggests RFA has less deleterious effect on quality of life than chemotherapy and that RFA patients recover quality of life significantly faster than chemotherapy recipients. It should be noted, however, that patients treated with RFA in different series may have better prognosis than those who undergo chemotherapy, suggesting patient selection bias may at least partially explain the apparent better outcomes observed following RFA. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Inoperable Hepatic Metastases of Neuroendocrine Origin

For individuals who have inoperable hepatic metastases of neuroendocrine origin who receive RFA, the evidence includes case series and a systematic review of case series. Relevant outcomes are OS, disease-specific survival, symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Most reports of RFA treatment for neuroendocrine liver metastases have assessed small numbers of patients or subsets of patients in reports of more than 1 ablative method or very small subsets of larger case series of patients with various diagnoses. The available evidence indicates that durable tumor and symptom control of neuroendocrine liver metastases can be achieved using RFA in individuals whose symptoms are not controlled by systemic therapy or who are ineligible for resection. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Hepatic Metastases Not of Colorectal or Neuroendocrine Origin

For individuals who have hepatic metastases not of colorectal or neuroendocrine origin who receive RFA, the evidence includes small nonrandomized comparative studies and small case series. Relevant outcomes are OS, disease-specific survival, symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Similar to primary HCC, resection appears to have the most favorable outcomes. For patients who are ineligible for resection, RFA may provide a survival benefit. Complete ablation of tumors was seen in >/= 90% of tumors in most studies; however, there was tumor recurrence. Although there are only small case series available, OS was documented as being at least 90% at 1year in 2 studies. The available evidence indicates that symptom control may be achieved using RFA, therefore the evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Percutaneous Ethanol Injection

For patients who have inoperable hepatocellular carcinoma, PEI can be considered. The evidence includes several RCTs, non- randomized trials and a comparative analysis. It has been noted that to achieve complete necrosis of liver tumors using PEI, multiple treatment sessions are usually needed.

Practice Guidelines and Position Statements

RFA:

American Association for the Study of Liver Diseases

The American Association for the Study of Liver Diseases (2018) published a guideline on the treatment of hepatocellular carcinoma. For adults with Child-Pugh class cirrhosis and resectable T1 or T2 hepatocellular carcinoma (HCC), the guideline suggests using resection over radiofrequency ablation (RFA; moderate quality/certainty of evidence; conditional strength of recommendation). Technical remarks in the guideline note that "Stage T1 and T2 HCC include a wide range of tumor sizes from <1 cm to 5 cm, and the effectiveness of available therapies depend in large part on the size, number, and location of the tumors. Whereas smaller, single tumors (<2.5 cm) that are favorably located may be equally well treated by either resection or ablation, tumors larger than 2.5-3 cm, multifocal, or near major vascular or biliary structures may have limited ablative options." Additionally, the guideline highlighted that "[r]andomized trials performed to date comparing RFA to resection have been performed primarily in East Asian patients, in whom there is a higher etiologic prevalence of HBV [hepatitis B virus] (including noncirrhotic HBV–associated HCC) and a lower prevalence of other liver diseases such as NAFLD [non-alcoholic fatty liver disease] or HCV [hepatitis C virus] compared with Western patients. The impact of these demographic differences on oncologic outcomes of different therapies is unknown."

Society of Interventional Radiology

The Society of Interventional Radiology published a position statement on percutaneous radiofrequency ablation for the treatment of liver tumors in 2009. It is the position of the Society that “percutaneous RF ablation of hepatic tumors is a safe and effective treatment for selected patients with HCC and colorectal carcinoma metastases” and that the current literature is insufficient to support any recommendations supporting or refuting the use of RFA in other diseases.

National Comprehensive Cancer Network

Several National Comprehensive Cancer Network (NCCN) guidelines are relevant to this review.

The National Comprehensive Cancer Network (NCCN) guidelines recommend:

  • The NCCN (v.2.2021) guidelines on hepatobiliary cancers note that "locoregional therapy should be considered in patients who are not candidates for surgical curative treatments, or as part of a strategy to bridge patients for other curative therapies." The guideline further states that "ablation alone may be curative in treating tumors ≤ 3 cm. In well-selected patients with small, properly located tumors, ablation should be considered as definitive treatment in the context of a multidisciplinary review. Lesions 3 to 5 cm may be treated to prolong survival using arterially directed therapies, or with combination of an arterially directed therapy and ablation as long as the tumor is accessible for ablation" (category 2A).
  • The NCCN (v.2.2021) guidelines on colon cancer metastatic to the liver state that "[a]blative techniques may be considered alone or in conjunction with resection. All original sites of disease need to be amenable to ablation or resection" (category 2A). Of all ablative techniques, the guidelines note that RFA has the most supporting evidence.
  • The NCCN (v.1.2021) guidelines for neuroendocrine tumors state that "percutaneous thermal ablation, often using microwave energy (radiofrequency and cryoablation are also acceptable), can be considered for oligometastatic liver disease, generally up to 4 lesions each smaller than 3 cm. Feasibility considerations include safe percutaneous imaging-guided approach to the target lesions, and proximity to vessels, bile ducts, or adjacent non-target structures that may require hydro- or aero-dissection for displacement [category 2B]." Additionally, "cytoreductive surgery or ablative therapies such as RFA or cryoablation may be considered if near-complete treatment of tumor burden can be achieved (category 2B). Ablative therapy in this setting is non-curative. For unresectable liver metastases, hepatic regional therapy (arterial embolization, chemoembolization, or radioembolization [category 2B]) is recommended."

Percutaneous Ethanol Injection:

National Comprehensive Cancer Network

The 2018 NCCN guidelines (v2.2018) state that “locoregional therapy should be considered in patients who are not candidates for surgical curative treatments, or as a part of a strategy to bridge patients for other curative therapies.” PEI is included in the locoregional therapies.

  • Tumors should be amenable to ablation, but a margin is not expected following PEI
  • Tumors should be accessible for ablation

U.S. Preventive Services Task Force Recommendations

RFA of tumors is not a preventive service.

KEY WORDS:

Locoregional liver therapy, Locoregional liver treatment, Radio-frequency Ablation (RFA), Percutaneous Ethanol Injection (PEI), liver cryotherapy, cryotherapy

APPROVED BY GOVERNING BODIES:

Chemoembolization for hepatic tumors is a medical procedure, and as such is not subject to FDA regulations.  However, the embolizing agents and drugs are subject to FDA approval.

Radiofrequency ablation devices have been cleared through the U.S. Food and Drug Administration (FDA) 510(k) process.

Several cryosurgical devices have clearance by the U.S. Food and Drug Administration (FDA). For example, the ENDOcare™ CRYOcare Cryosurgical System (Endocare, Inc., Irvine, CA) was cleared for marketing through the 510(k) process in December 1996 for “use in general surgery, dermatology, neurology, thoracic surgery, ENT, gynecology, oncology, proctology and urology for the ablation of tissue, including liver metastases, skin lesions, warts, and removal of prostate tissue.”

TheraSphere® has been granted Humanitarian Device Exception status by the FDA on December 10, 1999

SIR-Spheres was given a 510(k) PMA, March 5, 2002

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts:  Special benefit consideration may apply.  Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. 

CURRENT CODING:

CPT:

47370

Laparoscopy, surgical, ablation of one or more liver tumor(s); radiofrequency

47380

Ablation, open, of one or more liver tumor(s); radiofrequency

47382

Ablation, open, of one or more liver tumor(s); percutaneous, radiofrequency

47399

Unlisted procedure, liver

77013

Computerized tomography guidance for, and monitoring of, parenchymal tissue ablation

77022

Magnetic resonance guidance for, and monitoring of, parenchymal tissue ablation

77261

Therapeutic radiology treatment planning; simple

77262

Therapeutic radiology treatment planning; intermediate

77263

Therapeutic radiology treatment planning; complex

ICD-10-CM:

C22.0

Liver cell carcinoma

C22.1

Intrahepatic bile duct carcinoma

C22.2

Hepatoblastoma

C22.3

Angiosarcoma of liver

C22.4

Other sarcomas of liver

C22.8

Malignant neoplasm of liver, primary, unspecified as to type

C22.9

Malignant neoplasm of liver, not specified as primary or secondary

C24.0

Malignant neoplasm of extrahepatic bile duct

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

C7B.02

Secondary carcinoid tumors of liver

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  69. Knuppel M, Kubicka S, Vogel A et al. Combination of conservative and interventional therapy strategies for intra- and extrahepatic cholangiocellular carcinoma: a retrospective survival analysis. Gastroenterol Res Pract 2012; 2012:190708.
  70. Kutlu OC, Chan JA, Aloia TA, et al. Comparative effectiveness of first-line radiofrequency ablation versus surgical resection and transplantation for patients with early hepatocellular carcinoma. Cancer. May 15 2017; 123(10):1817-1827.
  71. Lan T, Chang L, Mn R, et al. Comparative efficacy of interventional therapies for early-stage hepatocellular carcinoma: A PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). Apr 2016; 95(15):e3185.
  72. Lee HJ, Kim JW, Hur YH, et al. Combined therapy of transcatheter arterial chemoembolization and radiofrequency ablation versus surgical resection for single 2-3 cm hepatocellular carcinoma: a propensity-score matching analysis. J Vasc Interv Radiol. Sep 2017;28(9):1240-1247 e1243.
  73. Lee SH, Jin YJ, Lee JW. Survival benefit of radiofrequency ablation for solitary (3-5 cm) hepatocellular carcinoma: An analysis for nationwide cancer registry. Medicine (Baltimore). Nov 2017;96(44):e8486.
  74. Li J, Zhang K, Gao Y, et al. Evaluation of hepatectomy and palliative local treatments for gastric cancer patients with liver metastases: a propensity score matching analysis. Oncotarget. Sep 22 2017;8(37):61861-61875.
  75. Li JK, Liu XH, Cui H, et al. Radiofrequency ablation vs. surgical resection for resectable hepatocellular carcinoma: A systematic review and meta-analysis. Mol Clin Oncol. Jan 2020; 12(1): 15-22.
  76. Li W, Bai Y, Wu M, et al. Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis. Oncotarget. Aug 8 2017;8(32):52132-52141.
  77. Li Z, Fu Y, Li Q, et al. Cryoablation plus chemotherapy in colorectal cancer patients with liver metastases. Tumour Biol. Nov 2014; 35(11):10841-10848.
  78. Liao M, Zhu Z, Wang H, et al. Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol. Jun - Jul 2017; 52(6-7):624-634.
  79. Lin Y, Pan XB. Differences in Survival Between First-Line Radiofrequency Ablation versus Surgery for Early-Stage Hepatocellular Carcinoma: A Population Study Using the Surveillance, Epidemiology, and End Results Database. Med Sci Monit. May 28 2020;26: e921782.
  80. Liu B, Huang G, Jiang C, et al. Ultrasound-Guided Percutaneous Radiofrequency Ablation of Liver Metastasis From Ovarian Cancer: A Single-Center Initial Experience. Int J Gynecol Cancer. Jul 2017;27(6):1261-1267.
  81. Liu H, Wang ZG, Fu SY, et al. Randomized clinical trial of chemoembolization plus radiofrequency ablation versus partial hepatectomy for hepatocellular carcinoma within the Milan criteria. Br J Surg. Mar 2016; 103(4):348-356.
  82. Liu Y, Li S, Wan X et al. Efficacy and safety of thermal ablation in patients with liver metastases. Eur J Gastroenterol Hepatol 2013; 25(4):442-6.
  83. Loveman E, Jones J, Clegg AJ et al. The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation. Health Technol Assess 2014; 18(7): vii-viii, 1-283.
  84. Majumdar A, Roccarina D, Thorburn D, et al. Management of people with early- or very early-stage hepatocellular carcinoma: an attempted network meta-analysis. Cochrane Database Syst Rev. Mar 28 2017; 3:Cd011650.
  85. Martin RC, Scoggins CR, Schreeder M, et al. Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer. Oct 15 2015; 121(20):3649-3658.
  86. Meijerink MR, Puijk RS, van Tilborg AAJM, et al. Radiofrequency and Microwave Ablation Compared to Systemic Chemotherapy and to Partial Hepatectomy in the Treatment of Colorectal Liver Metastases: A Systematic Review and Meta-Analysis. Cardiovasc Intervent Radiol. 2018 Aug;41(8):1189-1204. 
  87. Memon K, Lewandowski RJ, Mulcahy MF et al. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys 2012; 83(3):887-94.
  88. Michl M, Haug AR, Jakobs TF et al. Radioembolization with Yttrium-90 Microspheres (SIRT) in Pancreatic Cancer Patients with Liver Metastases: Efficacy, Safety and Prognostic Factors. Oncology 2014; 86(1):24-32.
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  101. National Comprehensive Cancer Network. Hepatobiliary Cancers. Version 3.2020. https://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf Accessed June 2, 2020.
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  106. Ng KM, Chua TC, Saxena A et al. Two decades of experience with hepatic cryotherapy for advanced colorectal metastases. Ann Surg Oncol 2012; 19(4):1276-83.
  107. Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo) embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011; (3):CD004787.
  108. Organ Procurement and Transplant Network. Policy 9: Allocation of Livers and Liver-Intestines. 2018;https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_09. Accessed June 9, 2020.
  109. Paprottka PM, Hoffmann RT, Haug A et al. Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres. Cardiovasc Intervent Radiol 2012; 35(2):334-42.
  110. Park SY, Kim JH, Yoon HJ et al. Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma. Clin Radiol 2011; 66(4):322-8.
  111. Pathak S, Jones R, Tand JMF, et al. Ablative therapies for colorectal liver metastases: a systematic review. Colorectal Dis 2011; 13(9):e252-65.
  112. Peng ZW, Zhang YJ, Liang HH, et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. Feb 2012; 262(2):689-700.
  113. Piduru SM, Schuster DM, Barron BJ et al. Prognostic value of 18f-fluorodeoxyglucose positron emission tomography-computed tomography in predicting survival in patients with unresectable metastatic melanoma to the liver undergoing yttrium-90 radioembolization. J Vasc Interv Radiol 2012; 23(7):943-8.
  114. Qi X, Tang Y, An D et al. Radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta-analysis of randomized controlled trials. J Clin Gastroenterol 2014; 48(5):450-7.
  115. Qi X, Wang D, Su C, et al. Hepatic resection versus transarterial chemoembolization for the initial treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Oncotarget. Jul 30 2015; 6(21):18715-18733.
  116. Riaz A, Gates VL, Atassi B, et al. Radiation segmentectomy: A novel approach to increase safety and efficacy of radioembolization. Int J Radiation Oncology Biol Phys 2010.
  117. Richardson AJ, Laurence JM, Lam VW. Transarterial chemoembolization with irinotecan beads in the treatment of colorectal liver metastases: systematic review. J Vasc Interv Radiol 2013; 24(8):1209-17.
  118. Riemsma RP, Bala MM, Wolff R, et al. Percutaneous ethanol injection for liver metastases. Cochrane Database Syst Rev. May 31 2013(5):CD008717.
  119. Rong G, Bai W, Dong Z, et al. Long-term outcomes of percutaneous cryoablation for patients with hepatocellular carcinoma within Milan criteria. PLoS One. 2015; 10(4):e0123065.
  120. Rosenbaum CE, Verkooijen HM, Lam MG et al. Radioembolization for treatment of salvage patients with colorectal cancer liver metastases: a systematic review. J Nucl Med 2013; 54(11):1890-5.
  121. Ruers T, Punt C, Van Coevorden F, et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. Oct 2012; 23(10):2619-2626.
  122. Ruers T, Van Coevorden F, Punt CJ, et al. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Inst. Sep 01 2017; 109(9).
  123. Saxena A, Bester L, Shan L et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol 2013.
  124. Saxena A, Chua TC, Chu F et al. Optimizing the surgical effort in patients with advanced neuroendocrine neoplasm hepatic metastases: a critical analysis of 40 patients treated by hepatic resection and cryoablation. Am J Clin Oncol 2012; 35(5):439-45.
  125. Schullian P, Johnston E, Laimer G, et al. Stereotactic Radiofrequency Ablation of Breast Cancer Liver Metastases: Short- and Long-Term Results with Predicting Factors for Survival. Cardiovasc Intervent Radiol. Apr 06 2021.
  126. Seidensticker R, Denecke T, Kraus P, et al. Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol 2012; 35(5):1066-73.
  127. Shen A, Zhang H, Tang C et al. A systematic review of radiofrequency ablation versus percutaneous ethanol injection for small hepatocellular carcinoma up to 3 cm. J Gastroenterol Hepatol 2013; 28(5):793-800.
  128. Shen WF, Zhong W, Liu Q et al. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study. World J Surg 2011; 35(9):2083-91.
  129. Shin SW, Ahn KS, Kim SW, et al. Liver Resection Versus Local Ablation Therapies for Hepatocellular Carcinoma Within the Milan Criteria: A Systematic Review and Meta-analysis. Ann Surg. Apr 01 2021; 273(4): 656-666.
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  131. Siperstein AE, Berber E. Cryoablation, percutaneous alcohol injection, and radiofrequency ablation treatment of neuroendocrine liver metastases. World J Surg 2001; 25(6):693-6.
  132. Smits ML, Prince JF, Rosenbaum CE et al. Intra-arterial radioembolization of breast cancer liver metastases: a structured review. Eur J Pharmacol 2013; 709(1-3):37-42.
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  134. Tian X, Dai Y, Wang DQ, et al. Transarterial chemoembolization versus hepatic resection in hepatocellular carcinoma treatment: a meta-analysis. Drug Des Devel Ther. 2015; 9:4431-4440.
  135. Tian X, Dai Y, Wang DQ, et al. Transarterial chemoembolization versus hepatic resection in hepatocellular carcinoma treatment: a meta-analysis. Drug Des Devel Ther. 2015; 9:4431-4440.
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  140. Veltri A, Gazzera C, Barrera M et al. Radiofrequency thermal ablation (RFA) of hepatic metastases (METS) from breast cancer (BC): an adjunctive tool in the multimodal treatment of advanced disease. Radiol Med 2014; 119(5):327-33.
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POLICY HISTORY:

TEC, December 2001

TEC, May 2001

Medical Review Committee, May 2001

Medical Policy Group, August 2002

Medical Policy Group, November 2002

Medical Policy Administration Committee, November 2002

Medical Policy Group, January 2003

Medical Policy Administration Committee, February 2003

Available for comments November 27, 2002-January 10, 2003

Available for comments February 7-March 25, 2003

Medical Policy Group, September 2004 (1)

Medical Policy Group, September 2006 (1)

Medical Policy Group, September 2008 (1)

Medical Policy Group, October 2009 (1)

Medical Policy Administration Committee, October 2009

Available for comment October 20-December 3, 2009

Medical Policy Group July 2010 (1): Added info in description and Key Points regarding radioembolization and radiofrequency

Medical Policy Administration Committee, August 2010

Available for comment August 5-September 18, 2010

Medical Policy Group, October 2010 (1): Description and Key points updated for TACE

Medical Policy Group, July 2011 (1): Update to Key Points and References related to cryotherapy, microspheres, PEI and RFA

Medical Policy Group, December 2011 (1): 2012 Code Update – verbiage change to code 77470

Medical Policy Group, April 2012 (1): Update to Policy, Key Points, Coding and References related to MPP update, microspheres and TACE; entire policy reformatted and streamlined; policy statement coverage criteria added related to liver mets for microspheres

Medical Policy Administrative Committee, May 2012

Medical Policy Group, July 2012 (1): Update to Key Points and References related to MPP update for RFA; no change to policy statement

Medical Policy Panel, March 2013

Medical Policy Group, June 2013 (1): Update to Key Points and References related to RE, TACE, cryoablation and microwave ablation; no change to policy statements

Medical Policy Panel, July 2013

Medical Policy Group, September 2013 (1): Update to Key Points and References related RFA; no change to policy statement

Medical Policy Panel, October 2013

Medical Policy Group, October 2013 (1): Update to Key Points and References related to MWA and TACE; no change to policy statements

Medical Policy Group, December 2013 (3):  2014 Coding Update – added new code 37243 to current coding effective 01/01/2014; moved code 37204 to previous coding (deleted effective 01/01/2014)

Medical Policy Panel, December 2013

Medical Policy Group, January 2013 (1): Update to Key Points and References related to cryosurgical ablation; no change to policy statement

Medical Policy Panel, March 2014

Medical Policy Group, March 2014 (1): Update to Key Points and References related to microspheres/radioembolization; no change to policy statement

Medical Policy Group, March 2014 (5): Added ICD-9 CM and ICD-10 CM diagnosis under Coding section; no change to policy statement

Medical Policy Group, June 2014 (3): Updated the Policy section with the addition of a statement referring readers to CareCore (included link) for Radioembolization or Intra-hepatic microshperes (TheraSpheres®, SIRSpheres®) effective August 1, 2014

Medical Policy Administration Committee, June 2014

Available for comment June 16 through July 31, 2014

Medical Policy Group, July 2014: Removed CareCore link and ‘Draft’. Transfer to CareCore is on hold until further notice.

Medical Policy Panel, July 2014

Medical Policy Group, July 2014 (1): Updated Key Points and References related to radio-frequency ablation; no change to policy statement

Medical Policy Group, November 2014: 2015 Annual Coding update.  Added CPT code 47383 to current coding.

Medical Policy Panel, December 2014

Medical Policy Group, February 2015 (4): Updates to Key Points and References related to Cryoablation.  No policy statement change.

Medical Policy Group, February 2015: Added Care Core draft link to radioembolization or intra-hepatic microspheres section of policy

Medical Policy Panel, October 2014

Medical Policy Group, February 2015(4): Updates to Key Points and References related to TACE. No policy statement change; Reorganized Key Points to be in same order as Description and policy statements. Added “refer to” statements under policy section. All policy statements remain unchanged.

Medical Policy Panel, August 2015

Medical Policy Group, August 2015 (4): Updates to Key Points, Approved Governing Bodies and References related to RFA.  Policy statements remain unchanged.

Medical Policy Panel, September 2015.

Medical Policy Group, October 2015 (4): Updates to Key Points, Approved Governing Bodies, and References related to TACE.  Policy statements unchanged.

Medical Policy Group, November 2015: 2016 Annual Coding Update. Moved 77776 and 77777 to previous coding.

Medical Policy Panel, December 2015

Medical Policy Group, December 2015 (4): Updates to Key Points, Approved Governing Bodies, and References relating to cryoablation. No change to policy statement.

Medical Policy Panel, August 2016

Medical Policy Group, August 2016 (4): Updates to Description, Key Points, and References relating to TACE and RFA. No change to policy statement.

Medical Policy Panel, June and July 2017

Medical Policy Group, July 2017 (4): Updates to Description, Key Points, and References.  Coding section updated by removing previously deleted codes from 2004 and 2007. Codes 76362, 76394, and 76490 were removed from the policy; Removed all aspects of microwave ablation from the policy. All information regarding MWA is on MP# 512 – Microwave Tumor Ablation.

Medical Policy Panel, July 2018

Medical Policy Group, July 2018 (4): Updates to Description, Key Points, Current Coding and References.  No change to policy statement. Removed ICD 9 diagnosis codes from Current Coding. Removed radioembolization HCPCS code and CPT codes from Current Coding (77300, 77370, 77470, 77750, 77778, 77790, 79445, 79900, S2095). Removed CPT code 37204 (deleted 2014) from Previous Coding.

Medical Policy Panel, July 2019

Medical Policy Group, August 2019 (4): Updates to RFA and TACE sections.  Updates to Key Points and References.  Previous coding section removed for 77776 and 77777. Codes deleted 1/1/16.

Medical Policy Group, October 2019 (5): Removed all information pertaining to Cryosurgical ablation (CSA) from this policy. Created separate MP for Cryosurgical Ablation of Primary or Metastatic Liver Tumors - MP 733. No change to Policy Statement.

Medical Policy Panel, July 2020

Medical Policy Group, August 2020 (5): Removed all information pertaining to Transcatheter Arterial Chemoembolization (TACE) from this policy including CPT codes 37243 and 75894. Created separate MP for Transcatheter Arterial Chemoembolization to Treat Primary or Metastatic Liver- MP 737. Updates to Description, Key Points, Practice Guidelines and Position statements, and References. Policy Statement updated to remove TACE. No change in Policy intent.

Medical Policy Panel, July 2021

Medical Policy Group, July 2021 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

 

 

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

 

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

 

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.