Medical Policy

 

Subject: Transcatheter Arterial Chemoembolization (TACE) and Transcatheter Arterial Embolization (TAE) for Malignant Lesions Outside the Liver except Central Nervous System (CNS) and Spinal Cord
Document #: RAD.00059 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018

Description/Scope

This document addresses the use of transcatheter arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE) for malignant lesions outside the liver, used as adjunct therapeutic interventions prior to operative resection or for palliation of symptoms.

Note:

Note: For additional information please refer to the following related documents:

Position Statement

Investigational and Not Medically Necessary:

Transcatheter arterial chemoembolization and transcatheter arterial embolization are considered investigational and not medically necessary for malignant lesions outside the liver.

Rationale

TACE and TAE are catheter-based embolization procedures performed with or without chemotherapeutic agents. TACE involves the regional injection of a form of chemotherapeutic or antitumor agent immediately followed by injection of an embolizing agent into the arterial vasculature supplying a tumor. TAE involves injecting an embolizing agent without a chemotherapeutic agent into the arterial vasculature. Both procedures have a tumoricidal effect on the targeted tumor(s) and have been proposed for tumor destruction, preoperative tumor bulk reduction and palliative treatment. While there are data in the peer-reviewed literature to support TACE and TAE for hepatic (liver) indications, there is limited evidence supporting their use for non-hepatic malignant indications.

TAE for Carotid Body Tumors

Bercin and colleagues (2015) conducted a small retrospective case review to determine the efficiency of preoperative embolization on vascular rupture rates during surgery in individuals with malignant carotid body tumors. A total of 13 records were included in the analysis that compared preoperative carotid body tumor embolization (n=7 cases) to no tumor embolization (n=6 cases). Data was collected on demographics, preoperative anatomical presentation of the carotid artery (including blood flow), tumor size, and complications of embolization (blood loss, other injury). The mean age of subjects was 48 years (range, 22-70 years); 12 of 13 subjects had stage II tumors with a mean diameter of 4.42 centimeters. Relative rates of blood flow reduction during embolization were greater than 50% in 4 subjects and 25%-50% in 3 subjects. Carotid artery injury was recorded in 4 embolized subjects (57%) and 1 non-embolized subject. There were no significant differences between carotid artery rupture and embolization, blood loss, tumor size, and supplying artery. The authors concluded that the benefit of embolization before surgical excision of carotid body tumor is “controversial” and “does not appear to be an advantage in reducing intraoperative blood loss, ease of dissection, and reducing the duration of the operative procedure following embolization.”

TACE and TAE for Kidney Cancer

Renal artery embolization (RAE) has been used as an adjunct procedure prior to resection of locally advanced renal tumors, but its role remains controversial given the lack of randomized prospective trials demonstrating a clinical benefit. Initially it was hypothesized that preoperative TAE may lead to improved survival in individuals with renal cell carcinoma (RCC) through immunomodulation, where TAE-induced tumor necrosis promoted tumor-specific natural killer cells (Bakke, 1982). Several older studies suggest potential clinical use.

Nurmi and colleagues (1987) studied RAE as palliative treatment of renal adenocarcinoma tumors ranging in size from 4 to 21 centimeters (cm) (mean size, 11 cm). At the time of embolization, 15 of the 25 study subjects had distant metastases to the lung (n=6), bony skeleton (n=3), liver (n=3), lungs/bones (n=2), and liver/bone (n=1). Severe pain (n=6) and gross hematuria (n=14) were the most frequent tumor-related symptoms; 5 subjects were treated for disease progression. A total of 24 subjects experienced post-procedure symptoms for 1 to 5 days. There was 1 death in a subject with an extensive history of cancer. Severe local pain due to the tumor was relieved in 3 of 6 subjects despite disease progression. Gross hematuria persisted in 3 of 14 subjects. This small study suggested that embolization could palliate pain but had no impact on disease progression or survival.

Zielinski and colleagues (2000) retrospectively compared the survival benefit of preoperative RAE followed by radical nephrectomy (n=118) to radical nephrectomy alone (n=116) in a matched group analysis of subjects selected from a series of 474 individuals with RCC. Individuals were selected for embolization based on preference of the urologist responsible for their care. As a result of this selection process, criteria for preoperative embolization was difficult to define; however, embolized subjects were expected to have T2-T3 tumors, tumors > 6 cms (as demonstrated on preoperative imaging studies), M0 disease, and good performance status. The timing of embolization prior to surgery ranged from 1 to 3 days (66 subjects, 56%), 4 days (22 subjects, 19%), and 5 to 13 days (30 subjects, 25%). Embolization was performed most frequently with a gelatin sponge product or wire coil device. The overall 5- and 10-year survival for the 118 subjects embolized before nephrectomy was 62% and 47%, respectively, and 35% and 23%, respectively for the matched group of 116 subjects treated with surgery alone (p=0.01). The reported favorable survival benefit associated with preoperative TAE for RCC needs to be interpreted with caution, as the data was derived from a nonrandomized, single-institution clinical trial.

Maxwell and colleagues (2007) studied a case series of 19 consecutive subjects undergoing palliative treatment of RCC with cytoreductive RAE. Unresectable disease and potentially resectable disease were present in 11 and 8 subjects, respectively with the latter determined to be unfit for surgery. Presenting symptoms included hematuria, pain, and nephrotic syndrome. Post-embolization syndrome occurred within 1 to 3 days. A total of 8 subjects experienced mild flank pain, 5 subjects developed fever, and 2 subjects experienced nausea. At study conclusion, 7 subjects were alive and 12 subjects had died (overall median survival,  6 months). The authors concluded that RAE is not a curative treatment and minimally altered the general course of the disease, but it did provide some palliation of local symptoms for advanced renal malignancy; therefore, comparison of cytoreductive embolization should be included in future studies of individuals with metastatic RCC.

TAE has been proposed to facilitate dissection secondary to resultant tissue plane edema, reduce blood loss, and decrease the extent of tumor thrombus in the preoperative management of RCC. These benefits have been evaluated in small case series and uncontrolled studies and have not been established in large, randomized, prospective trials. May and colleagues (2009) conducted a matched-pair retrospective study of individuals treated with RAE prior to nephrectomy (Group 1; n=189) or nephrectomy alone (Group 2; n=189) for RCC. Pairing of subjects was based on age, gender, clinical tumor size, grading, staging histology and microvascular invasion. Cancer specific survival and overall survival were defined as the primary endpoints. Cancer specific survival at 1, 5, and 8 years for Group 1 was 95%, 79%, and 70%; and, for Group 2, 93%, 83%, and 79% (p=0.085), respectively. Overall survival at 1, 5, and 8 years for Group 1 was 93%, 73%, and 62%; and, for Group 2, 91%, 75%, and 67%, respectively (p=0.677). Based on this data, the authors concluded that RAE prior to nephrectomy did not improve clinical outcomes or demonstrate a survival benefit for individuals with RCC.

Liu and colleagues (2008) conducted a randomized, prospective trial in China investigating TACE followed by tumor resection in children diagnosed with Wilms’ tumor. A cohort of 44 children (ages 6 months to 12 years) were randomized to treatment with preoperative TACE (n=24) or tumor resection alone (n=20, control group). The 2-year tumor-free survival rate was 83.3% in the TACE group compared to 10% in the control group (p<0.001). The rate of tumor recurrence and death within 1 year was 16.6% (4 of 24) in the TACE group compared to 60% (12 of 20) in the control group (p<0.001). While the results of this small study suggest that children with Wilms’ tumor may benefit from preoperative TACE, randomized comparative trials of larger sample size are needed to confirm these preliminary findings.

The current National Comprehensive Cancer Network® (NCCN) Clinical Practice Guideline (CPG) in Oncology® for kidney cancer (V3.2018) does not include a recommendation for the use of TACE or TAE for the treatment of RCC.

TACE and TAE for Bone Cancer

Yang and colleagues (2011) conducted a retrospective review of 60 individuals with sacral tumors to determine the value of preoperative TAE. The authors evaluated intraoperative blood loss, need for transfusion, treatment, local recurrence and surgical complications. There were no symptomatic complications associated with TAE. All tumors were resected without intraoperative shock or death. Subjects having surgery 1 day post-TAE had lower blood loss than those having surgery 2 to 3 days post-TAE, but the difference was not statistically significant (p=0.073 and p=0.086, respectively). With regard to surgical technique, subjects having a wide excisional margin (n=8) had no local recurrence or evidence of disease. Subjects having a marginal excision had local recurrence (6 of 34) and those having an intralesional excision had local recurrence (13 of 18). The average follow-up period was 75.2 months (range, 15 to 180 months), with 22 subjects presenting with varying degrees of neurological dysfunction in the form of motor weakness or loss of bowel/bladder control. Based on these findings, the authors concluded that preoperative TAE may significantly reduce intraoperative hemorrhage. Limitations of this study include lack of an active comparator control group and the retrospective design.

Koike and colleagues (2010) conducted a single center retrospective study evaluating both TACE and TAE as palliative treatments for symptomatic bone metastases. A total of 24 hypervascular lesions in 18 subjects were treated with either TACE or TAE. Devascularization of targeted lesions was obtained in 75% (18 of 24) of the lesions without serious complication. Pain relief was obtained in 20 lesions (83%) with a significant decrease in the visual analog scale (VAS) for pain score (5.08 pre-procedure VAS vs. 1.3 post-procedure; p<0.001). Mean time to pain relief was 1.6 days. Primary lesions included hepatocellular, colorectal, renal, ovarian, thyroid and cervical cancers. Symptomatic lesions treated were thoracic/lumbar spine, pelvis, rib and femur. The treatment effect of TACE and TAE was difficult to evaluate since subjects received a variety of adjuvant therapies including radiation therapy, bisphosphonates and steroids during their clinical course limiting comparison; in addition, the mean follow-up period was limited to 7.5 months (range, 1 to 29 months).

The NCCN CPG for bone cancer (V1.2018) includes a recommendation for the use of selective serial embolizations in the treatment of localized resectable giant cell tumor (GCT) of the bone (with unacceptable morbidity) and/or unresectable axial lesions. The category 2A recommendation is based on two single case studies, one case involving presurgical embolization of a proximal humerus tumor with cortical bone destruction extending to the shoulder joint (Emori, 2012) and a single case study involving embolization of a sacral tumor (Onishi, 2010). In addition, the NCCN cited two small retrospective case series (Hosalkar, 2007 [n=9]; Lin, 2002 [n=18]) that evaluated mid- to long-term outcomes of serial arterial embolization as primary treatment for large GCT of the sacrum. In the study by Lin and colleagues (2002), 14 of 18 subjects responded favorably to embolization with improvement in pain and neurologic symptoms. A total of 9 of 18 subjects also received intraarterial cisplatin as part of the treatment plan. There was 1 death that occurred 1 day after embolization. With long-term follow-up, 3 subjects developed late disease recurrences within the sacrum. Randomized trials comparing embolization to other therapies (such as, radiation, denosumab, and interferon) for the treatment of GCT of the bone have not been reported.

TACE and TAE for Metastatic Thyroid Cancer

The NCCN CPG for thyroid cancer (V2.2017) includes a recommendation to consider embolization as an option in the treatment of metastatic follicular, Hürthle cell, and papillary thyroid carcinoma when these tumors are not amenable to radioactive iodine (RAI) therapy. The therapeutic approach for metastatic disease depends on the site and number of tumor foci. Embolization (or other interventional procedures) of metastases may also be considered prior to surgical resection of bone metastases to reduce the risk of hemorrhage, or as an alternative to surgical resection, external beam radiation therapy, or intensity-modulated radiation therapy in select cases. The category 2A recommendation is based on a single study of the effects of selective embolization in individuals with symptomatic bone metastases from differentiated thyroid carcinoma. A total of 41 embolizations were performed in 16 individuals who were followed-up (range, 2 months to 8.6 years) after the first embolization by evaluation of clinical symptoms and tumor dimensions. Success was defined as an improvement in clinical symptoms without tumor progression. Embolization was reported as successful in 24 of 41 occasions (59%). A total of 26 embolizations were preceded or followed-up by additional therapies, consisting of surgery (laminectomy), external irradiation, or radioiodine. The authors reported, however, that subgroup analysis revealed the additional therapies did not influence the success rate, but a potential effect on success duration may have been present. For embolizations without additional radioiodine or external irradiation therapy, the median success duration was 6.5 months; for embolizations combined with additional radioiodine or external irradiation, the median success was 15 months (p=0.0146). The eventual health outcomes of these subjects were unfavorable, as 9 subjects died and 5 subjects had progressive disease. Despite a rapid induction and relief of symptoms, the treatment effect was transient and lacked durability (Eustatia-Rutten, 2003). For follicular, Hürthle cell, and papillary thyroid carcinoma, randomized comparative trials with other therapies, such as surgical palliation, radioiodine treatment, and/or external beam radiation, intravenous bisphosphonate, denusomab, and small molecular kinase inhibitors or systemic therapy have not been reported.

The NCCN recommendation for treatment of recurrent or persistent medullary thyroid carcinoma with symptomatic distant metastases (for example, those in the bone) includes “1) palliative resection, ablation (eg, radiofrequency, embolization), or other regional treatment;” or “vandetanib (category 1)”; or “carbozantinib (category 1).” “…These interventions may be considered for asymptomatic distant metastases (especially for progressive disease), but active surveillance is acceptable given the lack of data regarding alteration in outcome.”

Other Considerations

The current NCCN CPGs do not include a recommendation for TACE or TAE for the treatment of malignant lesions outside the liver for other cancers (except GCTB and metastatic thyroid cancer, as discussed above), including, colon, gastric, head and neck (such as, carotid body tumors), rectal, pancreatic, and prostate cancer.

Further study is needed to establish a clinical outcome benefit of TACE and TAE in the management of primary or metastatic tumors outside of the liver. Evidence published to date is limited to retrospective case series and single or small case reports. Prospective, randomized controlled trials are needed to better define the role of TACE and TAE in the management of these conditions.

Background/Overview

TACE and TAE have been proposed as alternatives to conventional systemic or intra-arterial chemotherapy as well as various nonsurgical ablative techniques for the treatment of resectable and nonresectable tumors. TACE and TAE target the arterial blood supply to tumors utilizing selective catheter-based infusion of particles, with or without chemotherapeutic agents. TAE involves the infusion of lipiodol (without a chemotherapeutic agent) and TACE involves the delivery of chemotherapeutic agents, either alone or in combination, mixed with a viscous embolic material, such as lipiodol. TAE may also involve the use of coils and balloons for embolization. Both TAE and TACE are followed by infusion of embolic agents, such as liquid embolitics (absolute alcohol), gelatin sponge particles, polyvinyl alcohol particles (PVA), or hydrophilic, polyacrylamide microporous beads (microspheres). The rationale for use of TACE is that infusion of viscous material containing one or more antineoplastic agents may exert synergistic effects on the tumor while minimizing systemic toxicities associated with oral or intravenous chemotherapy.

Definitions

Adenocarcinoma: A type of cancer that develops in cells lining glandular types of internal organs, such as the lungs, breasts, colon, prostate, stomach, pancreas, and cervix.

Palliative treatment: Treatment given for relief of symptoms and pain rather than effecting a cure.

Tumoricidal: Any treatment that is destructive to cancer cells.

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.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

CPT

 

37243

Vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumors, organ ischemia, or infarction

 

 

ICD-10 Diagnosis

 

 

For the following diagnoses when the procedure is related to treatment or palliation of symptoms of the malignant lesion outside the liver:

C00.0-C21.8

Malignant neoplasm of lip, oral cavity and pharynx, esophagus, stomach, small intestine, colon, rectosigmoid junction, rectum, anus and anal canal

C23-C26.9

Malignant neoplasm of gallbladder, other parts of biliary tract, pancreas, other digestive organs

C30.0-C49.9

Malignant neoplasm of respiratory and intrathoracic organs, bone and articular cartilage, skin, mesothelial and soft tissue

C50.011-C68.9

Malignant neoplasm of breast, female and male genital organs and urinary tract

C73-C76.8

Malignant neoplasm of thyroid and endocrine glands, neuroendocrine tumors

C77.0-C77.9

Secondary and unspecified malignant neoplasm of lymph nodes

C78.00-C78.6

Secondary malignant neoplasm of lung, respiratory organs, intestines, retroperitoneum and peritoneum

C78.80-C78.89

Secondary malignant neoplasm of other digestive organs

C79.00-C79.2

Secondary malignant neoplasm of kidney, bladder and other urinary organs, and skin

C79.51-C80.2

Secondary malignant neoplasm of other sites, and without specification of site

C81.00-C96.9

Malignant neoplasms of lymphoid, hematopoietic and related tissue

D00.00-D01.49

Carcinoma in situ of oral cavity, esophagus, stomach, colon, intestine

D01.7-D01.9

Carcinoma in situ of other digestive organs

D02.0-D09.9

Carcinoma in situ all other sites

References

Peer Reviewed Publications:

  1. Bakke A, Gothlin JH, Haudaas SA, Kalland T. Augmentation of natural killer cell activity after arterial embolization of renal carcinomas. Cancer Res. 1982; 42(9):3880-3883.
  2. Bercin S, Muderris T, Sevil E, et al. Efficiency of preoperative embolization of carotid body tumor. Auris Nasus Larynx. 2015; 42(3):226-230.
  3. Emori M, Kaya M, Sasaki M, et al. Pre-operative selective arterial embolization as a neoadjuvant therapy for proximal humerus giant cell tumor of bone: radiological and histological evaluation. Jpn J Clin Oncol. 2012; 42(9):851-855.
  4. Eustatia-Rutten CF, Romijn JA, Guijt MJ, et al. Outcome of palliative embolization of bone metastases in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2003; 88(7):3184-3189.
  5. Ginat DT, Saad WE, Turba UC. Transcatheter renal artery embolization for management of renal and adrenal tumors. Tech Vasc Interv Radiol. 2010; 13(2):75-88.
  6. Hosalkar HS, Jones KJ, King JJ, Lackman RD. Serial arterial embolization for large sacral giant-cell tumors: mid- to long-term results. Spine (Phila Pa 1976). 2007; 32(10):1107-1115.
  7. Koike Y, Takizawa K, Ogawa Y, et al. Transcatheter arterial chemoembolization (TACE) or embolization (TAE) for symptomatic bone metastases as a palliative treatment. Cardiovasc Intervent Radiol. 2011; 34(4):793-801.
  8. Li, J, Wang, S, Zee, C, et al. Preoperative angiography and transarterial embolization in the management of carotid body tumor: a single-center 10-year experience. Neurosurgery. 2010; 67 (4):941-948.
  9. Lin PP, Guzel VB, Moura MF, et al. Long-term follow-up of patients with giant cell tumor of the sacrum treated with selective arterial embolization. Cancer. 2002; 95(6):1317-1325.
  10. Liu WG, Gu WZ, Zhou YB, et al. The prognostic relevance of preoperative transcatheter arterial chemoembolization (TACE) and PCNA/VEGF expression in patients with Wilms tumour. Eur J Clin Invest. 2008; 38(12):931-938.
  11. Maxwell NJ, Saleem Amer N, Rogers E. Renal artery embolisation in the palliative treatment of renal carcinoma. Br J Radiol. 2007; 80(950):96-102.
  12. May M, Brookman-Amissah S, Pflanz S, et al. Pre-operative renal arterial embolisation does not provide survival benefit in patients with radical nephrectomy for renal cell carcinoma. Br J Radiol. 2009; 82(981):724-731.
  13. Nurmi M, Satokari K, Puntala P. Renal artery embolization in the palliative treatment of renal adenocarcinoma. Scand J Urol Nephrol. 1987; 21(2):93-96.
  14. Onishi H, Kaya M, Wada T, et al. Giant cell tumor of the sacrum treated with selective arterial embolization. Int J Clin Oncol. 2010; 15(4):416-419.
  15. Ramon, J, Rimon, U, Garniek, A, et al. Renal angiomyolipoma: lung-term results following selective arterial embolization, Eur Urol. 2009; 55(5): 1155-1161.
  16. Vogl TJ, Lehnert T, Zangos S, et al. Transpulmonary chemoembolization (TPCE) as a treatment for unresectable lung metastases. Eur Radiol. 2008; 18(11):2449-2455.
  17. Yang HL, Chen KW, Wang GL, et al. Pre-operative transarterial embolization for treatment of primary sacral tumors. J Clin Neurosci. 2010; 17(10):1280-1285.
  18. Zielinski H, Szmigielski S, Petrovich Z. Comparison of preoperative embolization followed by radical nephrectomy with radical nephrectomy alone for renal cell carcinoma. Am J Clin Oncol. 2000; 23(1):6-12.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. NCCN Clinical Practice Guidelines in Oncology® (NCCN). © 2017-2018 National Comprehensive Cancer Network, Inc. For additional information: http://www.nccn.org/index.asp. Accessed on March 15, 2018.
    • Bone Cancer (V1.2018). Revised August 29, 2017.
    • Kidney Cancer (V3.2018). Revised February 6, 2018.
    • Pancreatic Adenocarcinoma (V3.2017). Revised September 11, 2017.
    • Soft Tissue Sarcoma (V1.2018). Revised October 31, 2017.
    • Thyroid Carcinoma (V2.2017). Revised May 17, 2017.
Websites for Additional Information
  1. National Cancer Institute (NCI). Cancer Topics. Available at: https://www.cancer.gov/about-cancer. Accessed on March 15, 2018.
Document History

Status

Date

Action

Reviewed

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC review).

Reviewed

05/02/2018

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale, References, and Websites for Additional Information sections.

Revised

05/04/2017

MPTAC review.

Revised

05/03/2017

Hematology/Oncology Subcommittee review. Made minor typographical revision in the Position Statement section. Updated References section.

Reviewed

05/05/2016

MPTAC review.

Reviewed

05/04/2016

Hematology/Oncology Subcommittee review. Updated Rationale, References and Websites for Additional Information sections. Removed ICD-9 codes from Coding section.

Reviewed

05/07/2015

MPTAC review.

Reviewed

05/06/2015

Hematology/Oncology Subcommittee review. Updated Description, Rationale, and Websites for Additional Information sections.

Reviewed

05/15/2014

MPTAC review.

Reviewed

05/14/2014

Hematology/Oncology Subcommittee review. Updated Rationale, Background, Definitions, References, and Websites for Additional Information sections.

 

01/01/2014

Updated Coding section with 01/01/2014 CPT changes; removed 37204 deleted 12/31/2013, and 75894.

Revised

05/09/2013

MPTAC review.

Revised

05/08/2013

Hematology/Oncology Subcommittee review. Minor format change/clarification to the Position Statement. Updated Rationale, Background, Definitions, and References. Added Websites for Additional Information. Removed Index.

Reviewed

05/10/2012

MPTAC review.

Reviewed

05/09/2012

Hematology/Oncology Subcommittee review. Title changed to exclude CNS and spinal cord lesions. Rationale and References updated.

Reviewed

05/19/2011

MPTAC review.

Reviewed

05/18/2011

Hematology/Oncology Subcommittee review. Description, Rationale and References updated.

New

02/17/2011

MPTAC review. Initial document development.