Coverage Policy Manual
Policy #: 2003062
Category: Medicine
Initiated: December 2003
Last Review: July 2018
  Cryosurgical Ablation of Breast Tumors, Benign and Malignant

Description:
Cryosurgical ablation (hereafter, cryosurgery) involves freezing of target tissues, most often by inserting into the tumor a probe through which coolant is circulated. Cryosurgery may be performed as an open surgical technique or as a closed procedure under laparoscopic or ultrasound guidance.
 
The hypothesized advantages of cryosurgery include improved local control and benefits common to any minimally invasive procedure (e.g., preserving normal organ tissue, decreasing morbidity, decreasing length of hospitalization).  Potential complications of cryosurgery include those caused by hypothermic damage to normal tissue adjacent to the tumor, structural damage along the probe track, and secondary tumors, if cancerous cells are seeded during probe removal.
 
Recent publications report use of cryosurgery to treat breast cancer.  Early-stage primary breast tumors are treated surgically. The selection of lumpectomy, modified radical mastectomy, or another approach balances the patient’s desire for breast conservation, the need for tumor-free margins in resected tissue, and the patient’s age, hormone receptor status, and other factors. Adjuvant radiation therapy decreases local recurrences, particularly for those who select lumpectomy. Adjuvant hormonal therapy and/or chemotherapy are added, depending on presence and number of involved nodes, hormone receptor status, and other factors. Treatment of metastatic disease includes surgery to remove the primary lesion and combination chemotherapy. Fibroadenomas are common, benign tumors of the breast that can either present as a palpable mass or a mammographic abnormality. These benign tumors are frequently surgically excised to rule out a malignancy.
 
Coding   
There is a CPT code for cryosurgical ablation of fibroadenoma:
19105 Ablation, cryosurgical, of fibroadenoma, including ultrasound guidance, each fibroadenoma
 

Policy/
Coverage:
Cryosurgical ablation as a treatment of benign or malignant breast masses does not meet member benefit certificate primary coverage criteria, which excludes services which are being studied in Phase phase I, II or III clinical trials.
 
For contracts without primary coverage criteria, cryosurgical ablation as a treatment of benign or malignant breast masses is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
This policy is based on an analysis of relevant literature identified in a MEDLINE/PubMed search performed in July 2003. The literature search identified publications discussing application of cryosurgery for primary and metastatic tumors outside the liver and prostate. All were uncontrolled case series with varied criteria to select patients for cryosurgery, and reported limited data on long-term outcomes. Cryosurgical treatment of other tumors has been attempted, but evidence on outcomes of these uses is limited to isolated case reports.
 
The following section summarizes those studies that adequately described baseline characteristics of the patient populations and the methods used for cryosurgery, and also reported outcomes of treatment for 8 or more patients with the same diagnosis, or 8 or more procedures on the same malignancy. One article  discussed cryosurgery in 429 patients with a wide variety of primary and recurrent solid tumors (e.g., head and neck, lung, genital organs, sarcomas). Although the author reported survival for some patient subsets with certain of these malignancies, the article only reported baseline tumor and patient characteristics for those with breast cancer.
 
Three studies described the outcome of cryosurgery for advanced primary or recurrent breast cancer in 72 patients. Cryosurgery was performed percutaneously with ultrasound guidance (n=15) or during an open surgical procedure (n=57). Patients were treated for advanced primary disease (44%) or recurrent tumors (56%). Tanaka  reported the largest retrospective series: 9 patients with advanced primary tumors and 40 with recurrent disease. The author reported 44% survival of primary breast cancer patients (n=9) at 3 and 5 years, but did not report survival duration or other outcome for those with recurrent or metastatic disease. The report also did not adequately describe selection criteria for those enrolled in the study, details of the procedure, and procedure-related adverse events. The other studies were smaller series of patients and also were inadequate with respect to study design, analysis, and reporting of results. Furthermore, the study by Pfleiderer et al.  was a pilot trial to evaluate technical limitations of the procedure. Tumors were excised and evaluated by pathology days to weeks after cryosurgery, and the authors reported incomplete necrosis in tumors greater than 23 mm in diameter.  Because of these limitations, studies published to date do not permit conclusions regarding the effects of cryosurgery on health outcomes of patients with breast cancer.
 
One study described the use of office-based ultrasound-guided cryoablation as a treatment of breast fibroadenomas in 57 patients in whom a prior biopsy had confirmed the presence of a fibroadenoma. While this study reported that the procedure was technically feasible, only 20 of the 57 patients treated were followed up for 6 months after cryosurgery and only 3 were followed up for 12 months.  Thus, longer follow-up and further studies are required.
 
2010 Update
The policy is being updated with results of a search of the MEDLINE database through December, 2009.
 
In December 2005, the American Society of Breast Surgeons issued an updated consensus statement on the management of fibroadenomas of the breast.   This statement stated: “Several multi-institutional trials have demonstrated cryoablation to be a successful option for the resolution of fibroadenomas without surgical excision.” The statement also indicated: “Results of cryoablation have been followed out to 4 years and demonstrate the procedure to be safe, efficacious, and durable.” However, there were no controlled clinical trials identified to support these statements.
 
A small series of 11 patients with tumors less than 2 cm was found using cryoablation for treatment of breast cancer (Pusztaszeri, 2007).   In 6 cases, residual tumor was noted during follow-up lumpectomy about 4 weeks later.
 
In an editorial, White noted that pathologic assessment of margins is a critical component of the care of patients with breast cancer given that failure to achieve negative margins is associated with an elevated risk of local recurrence and called for large, rigorous trials before changing the care of these patients (White, 2008).  
 
The American College of Surgeons Oncology Group and the National Cancer Institute are conducting a Phase II trial to determine the rate of complete tumor ablation in patients with invasive ductal breast carcinoma treated with cryoablation (NCT00723294).
 
Treatment of Breast fibroadenoma.
While no comparative studies have been completed using cryoablation for this indication, additional follow-up studies have been reported. Kaufman reported on 37 women with follow-up averaging 2.6 years and noted that of the original 84% that were palpable prior to treatment, only 16% remained palpable and of the fibroadenomas that were initially 2 cm or less in size, only 6% remained palpable (Kaufman, 2005).  In this series of patients, the authors also noted that cryoablation did not produce artifact that might interfere with interpretation of mammograms. Nurko and colleagues reported on outcomes at 6 and 12 months for 444 treated fibroadenomas reported to the FibroAdenoma Cryoablation Treatment (FACT) registry involving 55 different practice settings (Nurko, 2005).  In these patients, before cryoablation, 75% of fibroadenomas were palpable by the patient. Follow-up at 6- and 12-month intervals showed palpable masses in 46% and 35%, respectively. When fibroadenomas were grouped by size, for lesions 2 cm or less, the treatment area was palpable in 28% at 12 months. For lesions more than 2 cm, the treatment area was palpable in 59% at 12 months. The authors noted they would continue to follow up these patients to better define resolution of the treatment-induced physical and radiographic findings. As noted above, comparative trials with adequate long-term follow-up is needed to assess this technology. How this approach compares with surgery as well as with vacuum-assisted excision and with observation (about one-third regress over several years’ time) was determined to need additional study.
 
The American Society of Breast Surgeons revised its statement on Management of Fibroadenomas of the Breast in April 2008 removing statements indicating that the society will monitor outcomes to provide updated guidance and encouraging physicians to place these patients in a registry where available to monitor long-term outcomes.
 
2011 Update
A literature search was conducted through July 2011.  One systematic review of minimally-invasive ablative techniques of early-stage breast cancer was identified (Zhao, 2010). The review noted that studies on cryoablation for breast cancer are primarily limited to pilot and feasibility studies in the research setting. Complete ablation of tumors was found to be reported within a wide range of 36-83%. Since there are many outstanding issues, including patient selection criteria and the ability to precisely determine the size of tumors and achieve 100% tumor cell death, the reviewers noted minimally-invasive thermal ablation techniques for breast cancer treatment, including cryoablation, should be limited until results from prospective, randomized clinical trials become available.
 
A search of ClinicalTrials.gov in June 2011 found no randomized controlled trials.  A Phase II Trial Exploring the Success of Cryoablation Therapy in the Treatment of Invasive Breast Carcinoma (NCT00723294) sponsored by the American College of Surgeons Oncology Group and the National Cancer Institute is ongoing.  In addition, the  Evaluation of Safety and Feasibility of the ICE-SENSE™, a Cryotherapy Device for Office-based Ultrasound-guided Treatment of Breast Fibroadenoma (NCT00910312) was identified.
 
This information does not prompt a change in the coverage statement.
 
2012 Update
A literature search conducted through September 2012 did not reveal any new randomized controlled trials that would prompt a change in the coverage statement.  One case series was identified in which 15 patients with breast cancer lesions that were 8 ± 4 mm in diameter had percutaneous cryoablation performed 30-45 days prior to surgical resection (Manenti, 2011).  Resection of the lesions confirmed complete necrosis occurred in 14 patients, but one lesion had residual disease considered to be probably due to incorrect probe placement.
 
Ongoing Clinical Trials
A search of the clinicaltrials.gov website in October 2012 found several ongoing studies assessing cryoablation for the treatment of breast tumors, including the following:
 
    • A phase II Trial Exploring the Success of Cryoablation Therapy in the Treatment of Invasive Breast Carcinoma (NCT00723294) sponsored by the American College of Surgeons Oncology Group and  the National Cancer Institute.
    • Evaluation of Safety and Feasibility of the ICE SENSE™, a Cryotherapy Device for Office-based Ultrasound –guided Treatment of Breast Fibroadenoma (NCT00910312).
    • A Pilot Study assessing Pre-Operative, Single-Dose Ipilimumab and/or Cryoablation in Early Stage/Resectable Breast Cancer (NCT01502592). This study is an open-label, non-randomized trial to study the safety, tolerability and efficacy of cryoablation alone versus Ipilimumab alone or Ipilimumab plus cryoablation.
 
Summary
The available evidence does not include control groups or compare outcomes of cryosurgery to alternative strategies for managing similar patients and no conclusions can be made on the net health outcomes of cryosurgery for breast cancer. Additionally, this treatment is still being studied in pilot and Phase II studies. Therefore, cryoablation for the treatment of benign or malignant breast tumors does not meet primary coverage criteria.
 
2013 Update
A literature search was conducted using the MEDLINE database through September 2013.  No new information was identified that would prompt a change in the coverage statement. One relevant study, summarized below, was identified.
 
Niu and colleagues reported on a 2013 retrospective study of 120 patients with metastatic breast cancer, including 30 metastases to the contralateral breast and other metastases to the lung, bone, liver and skin who were treated with either chemotherapy (n=29) or cryoablation (n=91,35 of whom also received immunotherapy) (Niu, 2013). After a 10-year follow-up, median overall survival of all study participants was 55 months in the cryoablation group versus 27 months in the chemotherapy group (p<0.0001). Median overall survival was also greater in patients receiving multiple cryoablations and in those receiving immunotherapy. Complications with cryotherapy to the breast were ecchymosis and hematoma, pain, tenderness and edema, all of which resolved within 1 week to 1 month.
 
2014 Update
A literature search conducted through June 2014 did not reveal any new information that would prompt a change in the coverage statement.
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement.  
 
2018 Update
A literature search was conducted through June 2018.  There was no new information identified that would prompt a change in the coverage statement.  

CPT/HCPCS:
19105Ablation, cryosurgical, of fibroadenoma, including ultrasound guidance, each fibroadenoma

References: Cryoablation for treatment of breast fibroadenomas. Hayes Assessment June 2002.

Cryoablation for treatment of breast fibroadenomas. Hayes Directory, Jan 2007.

Kaufman CS, Bachman B, et al.(2002) Office-based ultrasound-guided cryoablation of breast fibroadenoma. Am J Surg 2002; 184:384-400.

Kaufman CS, Bachman B, Littrup PJ, et al.(2004) Cyroablation treatment of benign breast lesions with 12 months follow up. Am J Surg 2004; 188(4):240-8.

Kaufman CS, Littrup PJ, Freeman-Gibb LA et al.(2005) Office-based cryoablation of breast fibroadenomas with long-term follow-up. Breast J 2005; 11(5):344-50.

Kaufman CS, Littrup PJ, Freman-Gibb LA, et al.(2004) Office-based cyroablation of breast fibroadenomas: 12-month followup. J Am Coll Surg 2004; 198(6): 914-23.

Littrup PJ, Freeman-Gibb L, Andea A, et al.(2005) Cryotherapy for breast fibroandenomas. Radiology 2005; 234(1):63-72.

Manenti G, Perretta T, Gaspari E et al.(2011) Percutaneous local ablation of unifocal subclinical breast cancer: clinical experience and preliminary results of cryotherapy. Eur Radiol 2011; 21(11):2344-53.

Niu L, Mu F, Zhang C et al.(2013) Cryotherapy protocols for metastatic breast cancer after failure of radical surgery. Cryobiology 2013.

Nurko J, Mabry CD, Whitworth P et al.(2005) Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg 2005; 190(4):647-51.

Pfleiderer SO, Freesmeyer MG, et al.(2002) Cryotherapy of breast cancer under ultrasound guidance: initial results and limitations. Eur Radiol 2002; 12:3009-14.

Pusztaszeri M, Vlastos G, Kinkel K et al.(2007) Histopathological study of breast cancer and normal breast tissue after magnetic resonance-guided cryotherapy ablation. Cryobiology 2007 June 2; epub ahead of print.

Simmons RM.(2003) Ablative techniques in the treatment of benign and malignant breast disease. J Am Col Surg 2003; 197:334-8.

Suzuki Y.(1995) Cryosurgical treatment of advanced breast cancer and cryoimmunological responses. Skin Cancer 1995; 10:19-26.

Tanaka S.(1995) Cryosurgical treatment of advanced breast cancer. Skin Cancer 1995; 10:9-18.

Tang K, Yao W, Li H, et al.(2014) Laparoscopic renal cryoablation versus laparoscopic partial nephrectomy for the treatment of small renal masses: a systematic review and meta-analysis of comparative studies. . J Laparoendosc Adv Surg Tech A. Jun 2014;24(6):403-410. PMID 24914926

The American Society of Breast Surgeons. Consensus Statement: Management of Fibroadenomas of the Breast. http://www.breastsurgeons.org/officialstmts/Management_of_Fibroadenomas_of_the_Breast_4-29-08.pdf

White RL Jr.(2008) Cryoablative therapy in breast cancer: no. J Surg Oncol 2008; 97(6):483-4.

Zhao Z, Wu F.(2010) Minimally-invasive thermal ablation of early-stage breast cancer: a systemic review. Eur J Surg Oncol 2010; 36(12):1149-55.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.