Latest Review Date: December 2023

Category: Surgical                             

Note: Coverage may be subject to legislative mandates, including but not limited to the following, which apply prior to the policy statements:

• Federal Women's Health and Cancer Rights Act (WHCRA)

In accordance with the mandate listed above, Axillary reverse mapping is covered when used to treat lymphedema resulting from a mastectomy and ordered by the individual’s treating physician.

POLICY:

Axillary reverse mapping/reverse lymphatic mapping performed to prevent lymphedema is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Surgery and radiotherapy for breast cancer can lead to lymphedema and are some of the most common causes of secondary lymphedema. Lymphedema is associated with a significant impact on quality of life, and there is no cure for lymphedema. Axillary reverse mapping, also called reverse lymphatic mapping, has been developed with the intent of sparing axillary lymph nodes and lymphatics during breast cancer surgery, minimizing disruption and potentially reducing the risk of subsequent lymphedema development.

Lymphedema

Lymphedema is an accumulation of fluid due to a disruption of lymphatic drainage. Lymphedema can be caused by congenital or inherited abnormalities in the lymphatic system (primary lymphedema) but is most often caused by acquired damage to the lymphatic system (secondary lymphedema). Breast cancer treatment is one of the most common causes of secondary lymphedema. Specific treatment-associated risk factors associated with lymphedema development include:

• Lymphadenectomy
• Dissection or disruption of axillary lymph nodes; increasing the number of dissected/disrupted lymph nodes increases lymphedema risk
• Radiation therapy

The risk of breast cancer-related lymphedema is also increased in overweight or obese individuals, and in those with postoperative infections.

Development of lymphedema may take months or years following breast cancer treatment, and the true prevalence of breast cancer-related lymphedema is unclear. Systematic reviews have found lymphedema rates up to 13% in individuals undergoing sentinel lymph node biopsy (SNLB) and as high as 77% in those undergoing axillary lymph node dissection (ANLD). The addition of radiation therapy to SNLB or ANLD may also increase risk of lymphedema. A prospective study of 1,815 individuals published in 2020 found a 5-year cumulative incidence of breast cancer-related lymphedema of 9.5%, which ranged widely from 8% to 30% when stratified according to type of treatment. The lowest incidence of lymphedema was found among those undergoing SLNB only (8%), increasing to 11% for SNLB + regional lymph node radiation, 25% for ANLD only, and 30% for ANLD + RLNR. While SNLB was associated with a lower lymphedema risk, some risk remains, particularly for those with multiple positive axillary nodes for whom the standard for care is ANLD with or without radiation.

Early and ongoing treatment of lymphedema is necessary. Conservative therapy may consist of several features depending on the severity of the lymphedema. Patients are educated on the importance of self-care including hygiene practices to prevent infection, maintaining ideal body weight through diet and exercise, and limb elevation. Compression therapy consists of repeatedly applying padding and bandages or compression garments. Manual lymphatic drainage is a light pressure massage performed by trained physical therapists or patients designed to move fluid from obstructed areas into functioning lymph vessels and lymph nodes. Complete decongestive therapy is a multiphase treatment program involving all of the previously mentioned conservative treatment components at different intensities. Pneumatic compression pumps may also be considered as an adjunct to conservative therapy or as an alternative to self-manual lymphatic drainage in patients who have difficulty performing self-manual lymphatic drainage. In patients with more advanced lymphedema after fat deposition and tissue fibrosis have occurred, palliative surgery using reductive techniques such as liposuction may be performed.

Axillary Reverse Mapping

Axillary reverse mapping (ARM) involves subcutaneous administration of blue dye, fluorescence (i.e., indocyanine green), or radioisotopes to allow for visualization of the lymphatic drainage pathways of the arm and breast. This visualization is intended to distinguish and enable preservation of axillary lymph nodes and lymphatics in individuals undergoing SLNB and/or ANLD. It is believed that because the axilla and breast have mostly separate drainage pathways, the risk of lymphedema is reduced by avoiding the removal of lymph nodes and lymphatics that only drain the axilla identified through ARM. In the event that ARM reveals that the axillary nodes cannot be spared, for example due to crossover of sentinel and axillary nodes, lymphatic physiologic microsurgery has been explored as a method to preserve the axillary nodes, though evidence is limited.

KEY POINTS:

This evidence review was created with a search of the PubMed database. The most recent literature update was performed through October 20, 2023.

Summary of Evidence:

For individuals with breast cancer undergoing sentinel lymph node biopsy (SLNB) who receive axillary reverse mapping (ARM), the evidence includes nonrandomized studies and systematic reviews of those studies. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Evidence from 2 systematic reviews found ARM identified axillary lymphatics in about 38% of individuals undergoing SLNB, with lymphedema rates of 2% to 3% in individuals who underwent ARM during SLNB. Other outcomes such as quality of life were not reported. The systematic reviews had numerous limitations, including unclear mean duration of follow-up and inclusion of only single-arm, uncontrolled studies. Evidence from well-designed RCTs or controlled cohort studies is needed to determine the net health benefit of ARM in SLNB. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with breast cancer undergoing axillary lymph node dissection (ALND) who receive ARM, the evidence includes randomized controlled trials (RCTs), nonrandomized studies, and systematic reviews of those studies. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Pooled evidence from a systematic review of 5 RCTs showed a lower risk of lymphedema with ARM compared with no ARM (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.13 to 0.29), and another systematic review of RCTs and nonrandomized studies found a pooled lymphedema prevalence of 14% and lower risk of lymphedema with ARM and preserved axillary lymph nodes compared with resected lymph nodes (OR, 0.27; 95% CI, 0.20 to 0.36). In the same review, ARM was associated with an 82% identification rate of axillary lymph nodes and lymphatics, and a crossover rate between ARM and sentinel lymph nodes of 12%. Other health outcomes, including quality of life, were not reported. The safety of ARM in ALND has not been established, and the rate of metastatic ARM nodes was 13% based on pooled analysis of 27 studies in one systematic review. ARM in ALND was associated with a lower risk of lymphedema in the largest RCT conducted to date, which was also included in the systematic reviews, but oncological safety could not be determined and the trial also had important study relevance and design limitations. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome

Practice Guidelines and Position Statements

American Society of Breast Surgeons

The 2022 American Society of Breast Surgeons consensus guideline on axillary management of patients with in-situ and invasive breast cancer indicates that axillary reverse mapping (ARM) is one of several promising techniques for prevention of lymphedema, but also states "well-designed prospective studies with uniform criteria for patient selection, procedure, and outcome assessment are needed." The guideline recommends considering ARM if it is readily available when axillary lymph node dissection (ALND) is required. 

The American Society of Breast Surgeons also published recommendations from an expert panel in 2017 that included prevention of breast cancer-related lymphedema. The panel stated that "emerging data on preventive surgical strategies with ARM and LYMPHA are promising and should be explored further with appropriate patients."

American Association of Plastic Surgeons

In 2017, the American Association of Plastic Surgeons sponsored a conference to create consensus statements and recommendations for surgical treatment and prevention of upper and lower extremity lymphedema. The 2021 publication of the consensus recommendations did not include any recommendations specific to the use of ARM, but the following general statement was included within the text of the publication: "mapping of the lymphatics is encouraged when harvesting lymph nodes adjacent to the limbs such as reverse lymphatic mapping to avoid lymphatics draining the limb and to minimize the risk of donor-site lymphedema."

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for prevention of lymphedema have been identified.

KEY WORDS:

Lymphedema, microsurgery, reverse lymphatic mapping, axillary reverse mapping, WHCRA, Women's Health and Cancer Rights Act

APPROVED BY GOVERNING BODIES:

Axillary reverse mapping for lymphedema is adjunctive to a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration (FDA). Mapping agents used to visualize lymphatic pathways (e.g., isosulfan blue, indocyanine green ) may be subject to FDA regulation.

BENEFIT APPLICATION:

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

ITS: Covered if covered by the Participating Home Plan

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING: 

CPT codes:   

REFERENCES:

1. American Society of Breast Surgeons. Consensus Guideline on Axillary Management for Patients with In-Situ and Invasive Breast Cancer: A Concise Overview. 2022.
2. Asdourian MS, Skolny MN, Brunelle C, et al. Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis. Lancet Oncol. Sep 2016; 17(9): e392-405.
3. Beek MA, Gobardhan PD, Schoenmaeckers EJ, et al. Axillary reverse mapping in axillary surgery for breast cancer: An update of the current status. Breast Cancer Res Treat. 2016;158(3):421-432.
4. Beek MA, Gobardhan PD, Klompenhouwer EG, Rutten HJT, Voogd AC, Luiten EJT. Ervaring met ‘axillary reverse mapping’ [Experiences with axillary reverse mapping]. Ned Tijdschr Geneeskd. 2020 Feb 25;164:D4222. Dutch.
5. Beek MA, Gobardhan PD, Klompenhouwer EG, Menke-Pluijmers MB, Steenvoorde P, Merkus JW, Rutten HJ, Voogd AC, Luiten EJ. A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer. Eur J Surg Oncol. 2020 Jan;46(1):59-64. doi: 10.1016/j.ejso.2019.08.003. Epub 2019 Aug 5.
6. Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy. Am J Surg. Oct 2009; 198(4): 482-7.
7. Casabona F, Bogliolo S, Valenzano Menada M, et al. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol. Sep 2009; 16(9): 2459-63.
8. Cemal Y, Pusic A, Mehrara BJ. Preventative measures for lymphedema: separating fact from fiction. J Am Coll Surg. Oct 2011; 213(4): 543-51.
9. Chang DW, Dayan J, Greene AK, et al. Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference. Plast Reconstr Surg. Apr 01 2021; 147(4): 975-993.
10. Connor C, McGinness M, Mammen J, et al. Axillary reverse mapping: a prospective study in women with clinically node negative and node positive breast cancer. Ann Surg Oncol. Oct 2013; 20(10): 3303-7.
11. Coriddi M, Dayan J, Sobti N, et al. Systematic Review of Patient-Reported Outcomes following Surgical Treatment of Lymphedema. Cancers (Basel). Feb 29 2020; 12(3).
12. Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: A new technique for maximizing safety in vascularized lymph node transfer. Plast Reconstr Surg. 2015;135(1):277-285.
13. Dean LT, Kumar A, Kim T, et al. Race or Resource? BMI, Race, and Other Social Factors as Risk Factors for Interlimb Differences among Overweight Breast Cancer Survivors with Lymphedema. J Obes. 2016; 2016: 8241710.
14. Deng H, Chen L, Jia W, et al. Safety study of axillary reverse mapping in the surgical treatment for breast cancer patients. J Cancer Res Clin Oncol. Dec 2011; 137(12): 1869-74.
15. Executive Committee of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology. 2020; 53(1): 3-19.
16. Faisal, M., Sayed, M.G., Antonious, K. et al. Prevention of lymphedema via axillary reverse mapping for arm lymph-node preservation following breast cancer surgery: a randomized controlled trial. Patient Saf Surg 13, 35 (2019). https://doi.org/10.1186/s13037-019-0217-1.
17. Gennaro M, Listorti C, Mariani L, Maccauro M, Bianchi G, Capri G, Maugeri I, Lozza L, De Santis MC, Folli S. Oncological safety of selective axillary dissection after axillary reverse mapping in node-positive breast cancer. Eur J Surg Oncol. 2021 Jul;47(7):1606-1610. doi: 10.1016/j.ejso.2020.10.031. Epub 2020 Nov 1.
18. Guo X, Jiao D, Zhu J, et al. The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials. Gland Surg. Apr 2021; 10(4): 1447-1459.
19. Han C, Yang B, Zuo WS, et al. The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. PLoS One. 2016; 11(2): e0150285.
20. Han JW, Seo YJ, Choi JE, et al. The efficacy of arm node preserving surgery using axillary reverse mapping for preventing lymphedema in patients with breast cancer. J Breast Cancer. Mar 2012; 15(1): 91-7.
21. Klompenhouwer EG, Gobardhan PD, Beek MA, Voogd AC, Luiten EJ. The clinical relevance of axillary reverse mapping (ARM): study protocol for a randomized controlled trial. Trials. 2013 Apr 25;14:111. doi: 10.1186/1745-6215-14-111.
22. Kuusk U, Seyednejad N, McKevitt EC, et al. Axillary reverse mapping in breast cancer: a Canadian experience. J Surg Oncol.Dec 2014; 110(7): 791-5.
23. Ma X, Wen S, Liu B, et al. Relationship between Upper Extremity Lymphatic Drainage and Sentinel Lymph Nodes in Patients with Breast Cancer. J Oncol. 2019; 2019: 8637895.
24. McLaughlin SA, DeSnyder SM, Klimberg S, et al. Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of Breast Cancer-Related Lymphedema, Recommendations from an Expert Panel: Part 2: Preventive and Therapeutic Options. Ann Surg Oncol. Oct 2017; 24(10): 2827-2835.
25. McLaughlin SA, Stout NL, Schaverien MV. Avoiding the Swell: Advances in Lymphedema Prevention, Detection, and Management. Am Soc Clin Oncol Educ Book. Mar 2020; 40: 1-10.
26. Naoum GE, Roberts S, Brunelle CL, et al. Quantifying the Impact of Axillary Surgery and Nodal Irradiation on Breast Cancer-Related Lymphedema and Local Tumor Control: Long-Term Results From a Prospective Screening Trial. J Clin Oncol. Oct 10 2020; 38(29): 3430-3438.
27. National Lymphedema Network Medical Advisory Committee. Lymphedema Risk Reduction Practices: Position Statement of the National Lymphedema Network. 2012.
28. Noguchi M, Yokoi M, Nakano Y. Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer. J Surg Oncol. Mar 01 2010; 101(3): 217-21.
29. Ochoa D, Korourian S, Boneti C, et al. Axillary reverse mapping: five-year experience. Surgery. Nov 2014; 156(5): 1261-8.
30. Parks RM, Cheung KL. Axillary reverse mapping in N0 patients requiring sentinel lymph node biopsy - A systematic review of the literature and necessity of a randomised study. Breast. Jun 2017; 33: 57-70.
31. Pusic AL, Cemal Y, Albornoz C, et al. Quality of life among breast cancer patients with lymphedema: a systematic review of patient-reported outcome instruments and outcomes. J Cancer Surviv. Mar 2013; 7(1): 83-92.
32. Rubio IT, Cebrecos I, Peg V, et al. Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer. J Surg Oncol. Jul 01 2012; 106(1): 89-93.
33. Sakurai T, Endo M, Shimizu K, et al. Axillary reverse mapping using fluorescence imaging is useful for identifying the risk group of postoperative lymphedema in breast cancer patients undergoing sentinel node biopsies. J Surg Oncol. May 2014; 109(6): 612-5.
34. Seyednejad N, Kuusk U, Wiseman SM. Axillary reverse lymphatic mapping in breast cancer surgery: A comprehensive review. Expert Rev Anticancer Ther. 2014;14(7):771-781.
35. Shao X, Sun B, Shen Y. Axillary reverse mapping (ARM): where to go. Breast Cancer. Jan 2019; 26(1): 1-10.
36. Tummel E, Ochoa D, Korourian S, et al. Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?. Ann Surg. May 2017; 265(5): 987-992.
37. U.S. Food and Drug Administration. Lymphazurin (Isosulfan Blue) Product Label.
38. U.S. Food and Drug Administration. Spy Agent Green (Indocyanine Green for Injection) Product Label.
39. Wijaya WA, Peng J, He Y, et al. Clinical application of axillary reverse mapping in patients with breast cancer: A systematic review and meta-analysis. Breast. Oct 2020; 53: 189-200.
40. Yuan Q, Wu G, Xiao SY, et al. Identification and Preservation of Arm Lymphatic System in Axillary Dissection for Breast Cancer to Reduce Arm Lymphedema Events: A Randomized Clinical Trial. Ann Surg Oncol. Oct 2019; 26(11): 3446-3454.

POLICY HISTORY:

Medical Policy Panel, December 2023

Medical Policy Group, December 2023 (6) Axillary mapping information transferred from MP 719 Surgical Treatments of Lymphedema. No change in policy intent. Policy on Draft 1/1/24-2/15/24.

MPAC December 2023

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.