Surgery Section - Cryosurgical Ablation of Miscellaneous Solid Tumors

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Cryosurgical ablation (hereafter referred to as 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 renal cell carcinomas, breast cancer, and pancreatic cancer.

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 the 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.

Pancreatic Cancer

Pancreatic cancer is a relatively uncommon solid tumor that occurs almost exclusively in adults. Surgical resection of tumors contained entirely within the pancreas is currently the only potentially curative treatment. However the nature of the cancer is such that few tumors are found at such an early and potentially curable stage. Patients with more advanced local disease or metastatic disease may undergo chemotherapy with radiation following resection. This is rarely curative but rather seeks to retard tumor growth or palliate symptoms.

Renal Cell Carcinoma, Liver and Prostate tumors

Localized renal cell carcinoma (RCC) is treated by radical nephrectomy or nephron-sparing surgery. Prognosis drops precipitously if the tumor extends outside the kidney capsule, since chemotherapy is relatively ineffective against metastatic RCC.

Primary and metastatic tumors in the liver are difficult to treat. Although surgical resection is still the gold standard for treatment, some patients cannot tolerate resection for reasons including poor hepatic reserve. Hepatic cryotherapy, because of the new technological advances in ultrasonography and cryoprobe development, has become a viable, less invasive alternative for treatment of patients with hepatic tumors that are not amenable to surgical resection.

Cryoablation is one of several methods available for treating clinically localized prostate cancer and may be considered as an alternative to radical prostatectomy or radiation therapy. The proposed advantages of cryosurgical ablation are that the procedure is less invasive than surgery and recovery time is much shorter.

Note: A separate policy addresses radiofrequency ablation of tumors (RFA) (Surgery Policy No. 92).

Policy/Criteria

Cryosurgical ablation for the treatment of kidney, liver, and prostate tumors may be considered medically necessary.

Cryosurgical ablation is considered investigational as a treatment of all other solid tumors including but not limited to benign or malignant breast cancer and pancreatic cancer.

Position Summary

Cryosurgical ablation is considered an acceptable alternate treatment of kidney, liver, and prostate tumors. Various nationally recognized societies and associations are listing this treatment for these indications as part of their clinical guidelines. (23-28) Specifically the National Comprehensive Cancer Network (NCCN) and National Institute for Clinical Excellence (NICE) lists cryosurgical ablation for certain subsets of patients or after certain treatments have failed for all indications. (23-28)

The focus of this position summary is on the indications for which there is lack of evidence for use of cryosurgical ablation.All publications identified to date were uncontrolled case series with varied patient selection criteria, and all 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. (2)

The following sections summarize 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). (3) 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.

Breast Cancer

Three studies described the outcome of cryosurgery for advanced primary or recurrent breast cancer in 72 patients. (3-5) 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. (3) 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 outcomes 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. (4-6) Furthermore, the study by Pfleiderer and colleagues was a pilot trial to evaluate technical limitations of the procedure. (4) 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.

One case series by Sabel and colleagues explored the role of cryoablation as an alternative to surgical excision as a primary treatment of early stage breast cancer. (7) This phase 1 study included 29 patients who underwent cryoablation of primary breast cancers measuring less than 2 cm in diameter, followed 1 to 4 weeks later by standard surgical excision. Cryoablation was successful in patients with invasive ductal carcinoma less than 1.5 cm in diameter and with less than 25% ductal carcinoma in situ identified in a prior biopsy specimen.

A variety of case series have focused on the role of cryosurgery as an alternative to surgical excision of benign fibroadenomas. One study described the use of office-based ultrasound-guided cryoablation as a treatment of 57 breast fibroadenomas in 47 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 for six months after cryosurgery, and only 3 were followed for 12 months. A 2004 publication provides the 12 month follow-up data. (9) At one year, 75% of the fibroadenomas were non-palpable. A total of 91% of patients were satisfied at 12 months. The same group of authors published a case series of cryosurgical ablation of 78 benign lesions in 68 patients with one-year follow-up. (10) While this case series included patients with benign breast nodules or nodular fibrocystic disease, 85% of patients had biopsy-proven fibroadenomas; thus it is likely that this case series included overlapping patients with the above study. Similarly, 75% of fibroadenomas became non-palpable at one year. Finally, the same group of investigators published a third case series of 42 fibroadenomas in 29 patients. (11) Again, overlap of patients is likely, and similar results were reported. These three small case series from the same group of investigators are inadequate to permit scientific conclusions. Additionally, it is unclear whether the most appropriate health outcome is a nonpalpable breast fibroadenoma, as they are benign lesions with only a very remote chance of malignant conversion. Complete surgical excision may be recommended primarily to allay patients’ concerns regarding harboring a palpable lesion.

In 2005, the American Society of Breast Surgeons issued a consensus statement regarding management of fibroadenomas of the breast that states, “Several multi-institutional trials have demonstrated cryoablation to be a successful option for the resolution of fibroadenomas without surgical excision…Results of cryoablation have been followed out to 4 years and demonstrate the procedure to be safe, efficacious, and durable.”  (12)  The only multi-institutional  study referenced in the consensus statement is the 2002 case series by Kaufman (8); a literature search did not identify additional multi-institutional studies from other groups of investigators.  The consensus statement also states, “Both techniques, in the setting of this benign disorder, are considered low risk for patients who could, if required, undergo surgical resection for unsuccessful (incomplete excision) treatment. Subsequent published updates did not alter the conclusions reached in their 2005 statement. The Society will continue to monitor outcomes to provide updated guidance as future multi- and single institutional registry data are reported at meetings and in the breast surgery literature.”

Published literature identified only 1 small series of 11 patients with tumors less than 2 cm was found using cryoablation for treatment of breast cancer. (20) In 6 cases, residual tumor was noted during follow-up lumpectomy about 4 weeks later.

While no comparative studies have been completed using cryoablation for breast fibroadenoma, 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. (21) 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. (22) 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) needs additional study.

Pancreatic Cancer

Kovach and colleagues reported on 10 cryosurgical ablations in 9 patients with unresectable pancreatic cancer using intraoperative ultrasound guidance during laparotomy. (18) The authors reported no intraoperative morbidity or mortality and that all patients had adequate pain control postoperatively. At the time of publication, all patients were dead at an average of 5 months postoperatively (range: 1–11 months). Because this pilot feasibility study did not include a control group or compare outcomes of cryosurgery to alternative strategies for managing similar patients, no conclusions are possible on the effects of cryosurgery for pancreatic cancer.

Published literature related to use of cryoablation in pancreatic cancer and other cancers either involved small numbers of patients or limited follow-up. There was no new published data that would alter the current policy criteria.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.92
2. Tanaka S. Looking back on cryosurgery in the 20th century in Japan: a review. Skin Cancer 2002;17(3):117-31
3. Tanaka S. Cryosurgical treatment of advanced breast cancer. Skin Cancer 1995;10:9-18
4. Pfleiderer SO, Freesmeyer MG, Marx C et al. Cryotherapy of breast cancer under ultrasound guidance: initial results and limitations. Eur Radiol 2002;12(12):3009-14
5. Suzuki Y. Cryosurgical treatment of advanced breast cancer and cryoimmunological responses. Skin Cancer 1995;10:19-26
6. Morin J, Traore A, Dionne G et al. Magnetic resonance-guided percutaneous cryosurgery of breast carcinoma: technique and early clinical results. Can J Surg 2004;47(5):347-51
7. Sabel MS, Kaufman CS, Whitworth P et al. Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial. Ann Surg Oncol 2004;11(5):542-49
8. Kaufman CS, Bachman B, Littrup PJ et al. Office-based ultrasound-guided cryoablation of breast fibroadenomas. Am J Surg 2002;184(5):384-400
9. Kaufman CS, Littrup PJ, Freman-Gibb LA et al. Office-based cryoablation of breast fibroadenomas: 12 month follow up. J Am Coll Surg 2004;198(6):914-23
10. Kaufman CS, Bachman B, Littrup PJ et al. Cryoablation treatment of benign breast lesions with 12 months follow up. Am J Surg 2004;188(4):340-48
11. Littrup PJ, Freeman-Gibb L, Andrea A e tal. Cryotherapy for breast fibroadenomas. Radiol 2005:234(1):63-72
12. The American Society of Breast Surgeons.  Consensus statement: management of fibroadenomas of the breast. www.breastsurgeons.org(Verified  07/15/08)
13. Rukstalis DB, Khorsandi M, Garcia FU et al. Clinical experience with open renal cryoablation. Urology 2001;57(1):34-9
14. Gill IS, Novick AC, Soble JJ et al. Laparoscopic renal cryoablation: initial clinical series. Urology 1998;52(4):543-51
15. Gill IS, Novick AC, Meraney AM et al. Laparoscopic renal cryoablation in 32 patients. Urology 2000;56(5):748-53
16. Gill IS, Remer EM, Hasan WA et al.  Renal cryoablation: outcome at 3 years.  J Urol  2005;173(6):1903-7
17. Nadler RB, Kim SC, Rubenstein JN et al. Laparoscopic renal cryosurgery: the Northwestern experience. J Urol 2003;170(4 Pt 1):1121-5
18. Shingleton WB, Sewell PE Jr. Cryoablation of renal tumours in patients with solitary kidneys. BJU Int 2003;92(3):237-9
19. Kovach SJ, Hendrickson RJ, Cappadonna CR et al. Cryoablation of unresectable pancreatic cancer. Surgery 2002;131(4):463-4
20. Pusztaszeri M, Vlastos G, Kinkel K et al. Histopathological study of breast cancer and normal breast tissue after magnetic resonance-guided cryotherapy ablation. Cryobiology 2007 June 2; epub ahead of print
21. Kaufman CS, Littrup PJ, Freeman-Gibb LA et al. Office-based cryoablation of breast fibroadenomas with long-term follow-up. Breast J 2005; 11(5):344-50
22. Nurko J, Mabry CD, Whitworth P et al. Interim results from the Fibroadenoma Cryoablation Treatment Registry. Am J Surg 2005; 190(4):647-51
23. http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf (verified 07/25/08)
24. http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf (verified 07/25/08)
25. http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf (verified 07/25/08)
26. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11084 (verified 07/25/08)
27. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11269 (verified 07/25/08)
28. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11125 (verified 07/25/08)

Cross References

Radiofrequency Ablation of Tumors (RFA), Regence Medical Policy Manual, Surgery, Policy No. 92

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