Clinical UM Guideline

 

Subject: Cryosurgical Ablation of Solid Tumors Outside the Liver
Guideline #: CG-SURG-61 Publish Date:    12/27/2017
Status: New Last Review Date:    11/02/2017

Description

This document focuses on the use of cryosurgical ablation (cryosurgery) as a treatment of prostate cancer, renal tumors and other solid tumors outside the liver. Cryosurgery involves freezing of target tissues, most often by inserting into the tumor a probe through which coolant is circulated.

Note: This document does not address the treatment of skin lesions, including basal and squamous cell carcinoma.

Note: For additional information, see the following:

Clinical Indications

Medically Necessary:

Cryosurgical ablation of the prostate is considered medically necessary as a treatment of prostate cancer.

Cryosurgical ablation for clinically localized, suspected renal malignancy is considered medically necessary for individuals with peripheral lesions that are less than or equal to 4 cm in diameter when one or more of the following criteria are met:

Not Medically Necessary:

Cryosurgical ablation of tumors outside the liver is considered not medically necessary when the above criteria are not met and for all other indications including, but not limited to benign or malignant breast tumors and pancreatic cancer.

Coding

The following codes for treatments and procedures applicable to this guideline 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.

Prostate:

CPT

 

55873

Cryosurgical ablation of the prostate (includes ultrasonic guidance and monitoring)

 

 

ICD-10 Procedure

 

 

For the following codes when specified as cryosurgical ablation:

0V500ZZ-0V504ZZ

Destruction of prostate [by approach; includes codes 0V500ZZ, 0V503ZZ, 0V504ZZ]

 

 

ICD-10 Diagnosis

 

C61

Malignant neoplasm of prostate

C79.82

Secondary malignant neoplasm of genital organs

D07.5

Carcinoma in situ of prostate

Renal:

CPT

 

50250

Ablation, open, 1 or more renal mass lesion(s), cryosurgical, including intraoperative ultrasound guidance and monitoring, if performed

50542

Laparoscopy, surgical; ablation of renal mass lesion(s), including intraoperative ultrasound guidance and monitoring, when performed [when specified as cryosurgical ablation]

50593

Ablation, renal tumor(s), unilateral, percutaneous, cryotherapy

 

 

ICD-10 Procedure

 

 

For the following codes when specified as cryosurgical ablation:

0T500ZZ-0T514ZZ

Destruction of kidney [left or right, by approach; includes codes 0T500ZZ, 0T503ZZ, 0T504ZZ, 0T510ZZ, 0T513ZZ, 0T514ZZ]

0T530ZZ-0T544ZZ

Destruction of kidney pelvis [left or right, by approach; includes codes 0T530ZZ, 0T533ZZ, 0T534ZZ, 0T540ZZ, 0T543ZZ, 0T544ZZ]

 

 

ICD-10 Diagnosis

 

 

All diagnoses

Other tumors:

CPT

 

19105

Ablation, cryosurgical, of fibroadenoma, including ultrasound guidance, each fibroadenoma

20983

Ablation therapy for reduction or eradication of 1 or more bone tumors (eg, metastasis) including adjacent soft tissue when involved by tumor extension, percutaneous, including imaging guidance when performed; cryoablation

32994

Ablation therapy for reduction or eradication of 1 or more pulmonary tumor(s) including pleura or chest wall when involved by tumor extension, percutaneous, including imaging guidance when performed, unilateral; cryoablation

48999

Unlisted procedure, pancreas [ when specified as cryosurgical ablation of pancreas tumor(s)]

 

 

ICD-10 Procedure

 

 

For the following codes when specified as cryosurgical ablation:

0H5T0ZZ-0H5V3ZZ

Destruction of breast [right or left or bilateral, by approach; includes codes 0H5T0ZZ, 0H5T3ZZ, 0H5U0ZZ, 0H5U3ZZ, 0H5V0ZZ, 0H5V3ZZ]

 

 

ICD-10 Diagnosis

 

 

All diagnoses

Discussion/General Information

Background/Overview

Cryosurgery, also called cryotherapy or cryosurgical ablation, is the use of extreme cold produced by liquid nitrogen (or argon gas) to destroy abnormal tissue. Cryosurgery may be used to treat tumors on the skin (external tumors), such as basal cell carcinoma, or tumors inside the body (internal tumors), such as prostate cancer and renal tumors.

When cryosurgery is used to treat tumors inside the body, liquid nitrogen or argon gas is circulated through a hollow instrument called a cryoprobe, which is placed in contact with the tumor. Imaging procedures such as ultrasound or MRI are used to guide the cryoprobe to the tumor location and monitor the freezing process. The monitoring process is important so freezing of the cells is limited to the tumor and its immediate area, limiting the amount of damage to nearby healthy tissue. The cryoprobe may be inserted into the tumor during an open or laparoscopic surgical procedure or may be inserted through the skin (percutaneously) and guided to the tumor using an imaging technique. During a cryosurgical procedure a ball of ice crystals forms around the probe, freezing nearby cells and killing them. The probe is then removed from the tumor and the frozen tissue thaws. The dead tissue is then naturally absorbed by the body. Sometimes more than one probe is used to deliver the liquid nitrogen to various parts of the tumor.

Cryosurgery does have side effects; however, they may be less severe than those associated with conventional surgery or radiation therapy. Side effects depend on the location of the tumor but may include bleeding, and in the case of treatment for prostate cancer, incontinence and urinary retention. In rare cases, cryosurgery may interact adversely with certain types of chemotherapy.

Cryosurgery may offer advantages over other methods of cancer treatment. It can be less invasive than surgery, involving only a small incision or insertion of the cryoprobe through the skin. Consequently, complications of surgery such as pain and bleeding may be minimized. Cryosurgery may require a shorter recovery time and a shorter hospital stay, or no hospital stay at all. Sometimes cryosurgery can be done using only local anesthesia.

Because physicians can focus cryosurgical treatment on a limited area, they may be able to avoid the destruction of nearby healthy tissue. The treatment may be safely repeated and may be used along with standard treatments such as surgery, chemotherapy, hormone therapy, and radiation. Cryosurgery may offer an option for treating cancers that are considered inoperable or that do not respond to standard treatments. Furthermore, it may be used for individuals who are not good candidates for conventional surgery because of their age or other medical conditions.

Cryosurgery of prostate cancer

Treatment options for prostate cancer include watchful waiting, surgical prostatectomy, various forms of radiation therapy and cryosurgery. Cryosurgery of the prostate is a minimally invasive alternative for the management of prostate cancer. The goal of prostate cryoablation is the destruction of the entire gland.

Cryosurgery for breast fibroadenomas

Fibroadenomas of the breast are a common benign tumor, which may be palpated or discovered by imaging techniques. Fibroadenomas are often observed or may be surgically excised if causing concern or discomfort. Cryosurgery has been proposed as a surgical alternative.

Cryosurgery for renal cell carcinoma or other renal tumors

Localized renal cell carcinoma (RCC) is treated by radical nephrectomy or nephron-sparing surgery. Cryosurgery has been proposed as an alternative to surgical excision, with the potential advantage of preserving functioning renal tissue.

Rationale

Prostate Cancer

Cryosurgical ablation for treatment of prostate cancer has been demonstrated to be a safe and effective treatment modality. Data from many small nonrandomized uncontrolled trials have established that cryoablation of prostate tumors demonstrates similar complication rates as external beam radiation therapy (EBRT) in terms of erectile dysfunction, obstruction, incontinence, and urethral stricture. The efficacy of cryoablation, as noted by post-operative biopsy results and recurrence rates, is similar to EBRT when treating prostate cancer. In 2017, the American Urological Association (AUA) issued a guideline in conjunction with the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO) titled Clinically Localized Prostate Cancer, providing broad support for the use of cryotherapy in prostate cancer.

The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guideline® for Prostate Cancer (V.2.2017) recommends cryosurgery as a minimally invasive local option for individuals with prostate cancer. The guidelines note cryosurgery may be used as salvage therapy after failed radiation.

Cryosurgical ablation continues to be studied in combination with other therapeutic modalities. There are clinical trials of various phases, including a phase III randomized trial, that are ongoing and the data have not been published.

Renal Cell Carcinoma and Other Renal Tumors

Surgical excision of small renal masses remains the standard of care with 5-year survival approaching 97%. The use of minimally invasive techniques such as cryoablation and radiofrequency ablation continues to increase (Kunkle, 2008; Kutikov, 2009).

Tanagho (2013) compared cryoablation to robot assisted partial nephrectomy in subjects with contrast enhancing renal masses that were concerning for renal cell carcinoma (RCC). This retrospective nonrandomized controlled study involved 267 subjects who underwent either laparoscopic (n=149) or percutaneous (n=118) cryoablation versus 233 subjects who received treatment with robot-assisted partial nephrectomy. The authors reported no significant differences between the cryoablation and nephrectomy groups with regard to perioperative complication rates (8.6% vs. 9.4%, respectively; p=0.75). Biopsy results were reported in only 153 (57%) of the 267 subjects in the cryoablation group, with confirmed RCC in 52.3% (80/153) of subjects. Five-year Kaplan-Meier estimated disease-free survival (DFS) was 93.1%, cancer-specific survival (CSS) was 96.4%, and overall survival (OS) was 77.1%. In the nephrectomy group, all subjects had biopsy results and RCC was confirmed in 79.4%. In this group, DFS was 100%, CSS was 100%, and OS was 91.7%. Unfortunately, no intergroup comparative statistical data were provided for these data points. A statistically significant difference was noted in favor of the nephrectomy group versus the cryoablation group with regard to intraoperative complications (1.3% vs. 7.2%, respectively; p<0.01). This finding was reversed for postoperative complications (7.7% vs. 2.2%, respectively; p<0.01). Cancer recurrence was also significantly better with nephrectomy, with 12.7% of the cryoablation group experiencing recurrence versus 0% in the nephrectomy group (p<0.01). It should be noted that there were significant differences between groups preoperatively with regard to several factors, including mean tumor size (2.5 cm for the cryoablation vs. 2.9 cm for the nephrectomy group), the Charleston Comorbidity Index (6.5 vs. 2.1, respectively), and mean nephrectomy score (6.4 vs. 7.3, respectively).

Several nonrandomized and retrospective studies comparing nephrectomy with cryoablation have also been published that have demonstrated similar outcomes with regard to operative times, blood loss, and complication rates (Emara, 2014; Haramis, 2012; Panumatrassamee, 2013). Two of these studies (Emara, 2014; Panumatrassamee, 2013) reported significantly better post-operative renal function following cryoablation.

Atwell (2013) published the findings of a large retrospective review, which included 285 subjects with 445 tumors < 3 cm. Radiofrequency ablation (RFA) was used to treat 256 tumors in 222 subjects and cryoablation was used for 189 tumors in 163 subjects. In the RFA group, 59% (152/256) of tumors were biopsied and 54% (82/152) were identified as RCC. For the cryoablation group, 74% (140/189) of tumors were biopsied and 56% (79/140) were confirmed as RCC. Significant differences between groups at baseline were identified, with RFA subjects more likely to have had previous history of RCC (p=0.043) and more likely to have larger tumors than cryoablation subjects (2.3 cm vs. 1.9 cm; p<0.01). Overall, there were differences between groups with regard to technical failures (1 in the RFA group and 4 in the cryoablation group, p=0.17). No significant differences were noted with regard to rates of major complications (p=0.91). Follow-up of at least 3 months occurred in 60% of RFA tumors and only 40% of cryoablation tumors. For biopsy-proven RCC, estimated local recurrence-free survival rates at 1, 3, and 5 years after RFA were 100%, 98.1%, and 98.1%, respectively, compared with 97.3%, 90.6%, and 90.6%, respectively, after cryoablation (p=0.09).

Several nonrandomized studies using cryosurgery have been reported. Two of these reported follow-up data at a mean of 20 months (Breen, 2013; Buy, 2013). The Breen study, which prospectively enrolled 147 subjects, reported that only tumor location in the upper pole was a predictive factor for complications. Only one case of recurrence was reported with the subset of 62 subjects with biopsy-proven RCC. The Buy study prospectively enrolled 95 subjects and reported a technical success rate of 94%. The 12-month OS rate was 96.7% and disease-free survival (DFS) rate was 96.4%.

A large nonrandomized comparative study investigating the outcomes between laparoscopic (n=275) and percutaneous (n=137) cryoablation of single renal masses was published by Zargar in 2015. The overall and major complication rates were similar (7.27% vs. 7.29% and 0.7% vs. 3.6%, respectively). Estimated probability of 5-year OS for laparoscopic and percutaneous cryoablation was 89% and 82%, respectively. The estimated probability of the 5-year recurrence-free survival (RFS) was 79% and 80%, respectively. There was no significant difference in OS or RFS at 5 years between the two groups. The authors noted that heart disease (hazard ratio [HR]=2.15; p=0.001) and history of disease recurrence (HR=2.49; p<0.0001) were predictors of death. The median follow-up time for the laparoscopic group was longer than the percutaneous group (mean 4.41 years vs. 3.15 years; p=0.0001). However, tumor size and anterior location affected local recurrence rates, and these factors should be taken into consideration when choosing the appropriate treatment plan.

Caputo and colleagues published the results of a retrospective case series in 2016 to better understand the long-term outcomes of cryoablation for renal tumors. This study involved 138 subjects with 142 renal tumors treated with laparoscopic cryoablation. Of the 142 tumors, 100 were diagnosed as RCC. In the subjects with renal carcinoma, at 3, 5 and 10 year follow-up time points, the estimated recurrence-free survival was 91.4%, 86.5% and 86.5%, respectively. Estimated cancer specific survival was 96.8%, 96.8% and 92.6%, respectively, and estimated OS was 88.7%, 79.1% and 53.8%, respectively. The mean follow-up was 98.8 ± 54.2 months in subjects diagnosed with RCC. The authors reported a mean time to recurrence of 2.3 years with the latest experienced recurrence occurring 4.4 years after the intervention. It was noted that 3 subjects experienced incomplete ablation, with 1 subject undergoing repeat cryoablation and the other 2 undergoing radical nephrectomy. There was a postoperative complication rate of 10.6% with a total of 15 complications; the most common were ileus (n=3), hypoxia (n=2), and hemorrhage (n=2). The authors concluded that laparoscopic cryoablation achieved good long-term oncologic outcomes for localized small renal masses.

A meta-analysis by El Dib and colleagues (2012) evaluated cryoablation compared to RFA as a treatment of small (less than 4 cm) RCC. Cryoablation had a pooled clinical efficacy rate of 89% in 457 cases versus 90% in 426 cases with RFA. The rate of complications between the ablation techniques was not statistically significant. The authors concluded both cryoablation and RFA were promising therapies to treat small renal tumors in individuals who were considered poor candidates for more involved surgery.

In a meta-analysis, Kunkle (2008) reviewed 1375 renal masses that were ablated by cryoablation (n=600) or RFA (n=775) in 47 studies. RCC was confirmed in 53.9% of all ablated lesions. Local tumor progression was significantly less with cryoablation 5.2% (31/600 lesions) versus 12.9% (100/775 lesions) with RFA (p<0.0001).

The available, peer-reviewed medical literature reveals that cryoablation is safe and effective for: managing small, undefined peripheral renal masses (less than 4 cm); treating solitary kidneys or situations where the contra-lateral kidney is functioning poorly; and treating individuals who have significant comorbidities and cannot tolerate nephrectomy.

The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guideline® for Kidney Cancer (V.1.2018) includes surgical resection as an effective therapy for clinically localized RCC with options including radical nephrectomy and nephron-sparing surgery. Individuals with stage I through III tumors, who are in satisfactory medical condition, are recommended to undergo surgical excision. Active surveillance or ablative techniques, such as cryoablation or radiofrequency ablation are alternative strategies for individuals with T1 renal lesions who are not surgical candidates (e.g., the elderly; those with competing health risk factors).

The National Institute for Health and Clinical Excellence (NICE, 2011) guidance on cryoablation for renal cancer states that current evidence suggests that cryotherapy for renal cancer ablates tumor tissue and that its safety is adequate. Cryoablation is described as a possible treatment option for small tumors (less than 4 cm), for maximum preservation of renal function in individuals with a solitary kidney or compromised renal function or for those unfit for or unwilling to undergo major surgery.

The AUA published 2017 guidelines addressing renal mass and localized renal cancer including the following recommendation:

Both radiofrequency ablation and cryoablation are options for patients who elect thermal ablation. (Conditional Recommendation; Evidence Level: Grade C)

Additionally, the AUA makes the following general statement regarding thermal ablation (TA):

A multitude of techniques/technologies have been investigated to ablate renal tumors, however radiofrequency ablation (RFA) and cryoablation have been most widely investigated and integrated into clinical practice. While the superiority of RFA or cryoablation remains controversial, it is generally accepted that oncologic outcomes are similar for both approaches.

Other Indications

Bone Cancer and Bone Metastases

The use of cryoablation as a treatment for painful bone metastases continues to be investigated. The published medical literature on cryoablative therapy is based on case reports, case series and review articles.

Callstrom and colleagues (2012) reported results from a prospective case series of 61 subjects investigating percutaneous cryoablation to treat painful bone metastases. The primary endpoints were worst pain and average pain scores on a visual analog scale. Participants completed questionnaires prior to therapy, a day after cryoablation, and thereafter via telephone interview on day 4 and then every 2 weeks for up to 6 months. During the 24 week follow-up period, a total of 45 participants (74%) dropped out of the study. There was no significant change in the worst-pain score from baseline (7.1/10) to the interview at day 1 (7.0/10). The worst pain dropped significantly at week 1 to 5.1/10 (p<0.0001). Out of the 35 participants who were followed for a minimum of 8 weeks, 5 participants (14%) had recurrent worst pain that was equal to or greater than the baseline pain level prior to cryoablation. Of note, study participants were a subset of individuals included in multiple radiation treatment trials.

In a small case series, Meftah (2013) evaluated the outcomes of curettage and cryosurgery of low-grade chondrosarcoma of the bone in 42 subjects comparing a cryoprobe to a modified Marcove pour technique. There were no differences between the cryoprobe and Marcove techniques with respect to the Musculoskeletal Tumor Society score, fracture, or local recurrence. A significant correlation between tumor recurrence and soft-tissue extension was found (r=0.79). Kaplan-Meier survivorship, with freedom from recurrence as the endpoint, was 90.7%.

The NCCN clinical practice guidelines for cancer pain (V.2.2017) do not include cryoablation therapy as a technique to treat painful bone metastases.

Breast Cancer

A systematic review of minimally invasive ablative techniques of early stage breast cancer by Zhao (2010) noted studies on cryoablation for breast cancer are primarily limited to pilot and feasibility studies in the research setting. Complete ablation of breast tumors was reported within a wide range of 36%-83%. Although the published data provided information on technical feasibility, large randomized controlled studies are required to evaluate the long-term outcomes of minimally invasive thermal ablation techniques compared with current breast conserving therapies (Zhao, 2010).

Three studies described the outcome of cryosurgery for advanced primary or recurrent breast cancer in 72 individuals. Cryosurgery was performed percutaneously with ultrasound guidance (n=15) or during an open surgical procedure (n=57). Individuals were treated for advanced primary disease (44%) or recurrent tumors (56%). Tanaka reported the largest retrospective series which included 9 individuals with advanced primary tumors and 40 with recurrent disease. The author reported 44% survival of individuals with primary breast cancer (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 and also were inadequate with respect to study design, analysis, and reporting of results. Furthermore, the pilot study by Pfleiderer (2002) evaluated the 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.

Littrup and colleagues (2009) reported results from a nonrandomized feasibility study investigating multiprobe cryoablation as a treatment of 22 breast cancer lesions in 11 individuals who refused surgery. Participants consented to subsequent therapy with radiation therapy and/or chemotherapy with or without hormone therapy. Mean pretreatment tumor diameter was 1.7 cm (range, 0.5 cm to 5.8 cm). Average clinical follow-up was 22.8 months and average imaging follow-up was 17.5 months. Three participants were lost to follow-up. Two individuals had post-procedure biopsies confirming no local recurrence. One participant had a distant malignant lesion develop. Local success rate at 18 months was 100%. Although technical feasibility of cryoablation as a treatment of breast cancer appears promising, safety and efficacy outcomes have not been established.

The NCCN Breast Cancer Clinical Practice Guidelines (V.2.2017) do not include cryoablation as a modality to treat breast cancer.

There continue to be ongoing, nonrandomized phase II and phase III clinical trials investigating the use of cryosurgical ablation of breast cancer.

The American Society of Breast Surgeons (ASBS, 2017) has provided recommendations for cryoablation of malignant tumors of the breast. Specifically, they state:

Percutaneous and/or transcutaneous treatments of malignant tumors of the breast are not specifically approved by the FDA, though some ablative technologies are approved for treatment of benign and malignant soft tissue tumors. Therefore, ablative and percutaneous excisional treatments for breast cancer are considered investigational and should not be performed outside the realm of a clinical trial.

Breast Fibroadenomas

One study described the use of office-based ultrasound-guided cryoablation as a treatment of breast fibroadenomas in 57 individuals 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 individuals 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. Additionally, uncontrolled case series published in 2004 (and funded by the device manufacturer) suggested that cryoablation may be safe and initially effective in treating breast fibroadenomas (Edwards, 2004; Kaufman, 2005). However, a 2005 analysis of 444 treated fibroadenomas from a multi-center registry cautioned that palpability of the treated site may persist for months after the procedure in a significant percentage of individuals, and urged that surgeons, especially in individuals with larger fibroadenomas, consider this factor carefully when deciding between cryoablation and open surgical removal of the lesion. The paper cautions that, even though individual satisfaction with the cosmetic outcome of the procedure appeared generally high, longer-term follow-up is necessary to better understand the time course for resolution of both radiographic and physical findings in such individuals (Nurko, 2005).

The American Society of Breast Surgeons (ASBS, 2017) has provided recommendations for cryoablation or percutaneous excision of fibroadenoma, which include: that the lesion should be sonographically visible, histologically confirmed to be a fibroadenoma, the diagnosis of fibroadenoma must be concordant with the imaging findings, patient history, and physical exam, and the lesions should less than 4 cm in size.

The use of cryosurgery as a treatment for breast fibroadenomas has been reported in small case series. Although technical feasibility of cryoablation appears promising, the safety and efficacy of cryoablation versus surgical excision has not been established, compared to alternative treatment options.

Pancreatic Cancer

Kovach (2002) reported 10 cryosurgical ablations in 9 individuals with unresectable pancreatic cancer using intraoperative ultrasound guidance during laparotomy. The authors report no intraoperative morbidity or mortality and that all individuals had adequate pain control postoperatively. At the time of publication, all individuals had expired 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 individuals, no conclusions are possible on effects of cryosurgery for pancreatic cancer.

The NCCN Pancreatic Cancer Clinical Practice Guideline (V.3.2017) does not include cryoablation as a therapeutic modality to treat pancreatic cancer.

There is an ongoing phase I, nonrandomized clinical trial investigating the use of cryosurgical ablation to treat pancreatic cancer. To date, the outcomes from this trial have not been published.

Pulmonary Tumors

Cryosurgical ablation for the treatment of non-small cell lung cancer (NSCLC) has been studied in a limited number of small studies. The largest currently available was a case series study involving 47 subjects with NSCLC followed for a minimum of 5 years after treatment with cryoablation (Moore, 2015). The authors reported that the 5-year survival rate was 67.8% ± 15.3, the cancer-specific survival rate at 5 years was 56.6% ± 16.5, and the 5-year progression-free survival rate was 87.9%. The combined local and regional recurrence rate was 36.2%. Major complications were reported in 6.4% of subjects, with two cases of hemoptysis and a prolonged placement of a chest tube requiring mechanical sclerosis in 1 subject. No deaths occurred in the first 30 days after treatment. These results are promising, but results from a large, controlled, comparative trial are needed for a better understanding of the safety and efficacy of cryoablation for NSCLC.

The NCCN Clinical Practice Guideline for non-small cell lung cancer (V.7.2017) notes pulmonary resection is the preferred local treatment modality for non-small cell lung cancer. Cryoablation is listed as an off-label modality, but there is no evidence provided to support this approach. The guidelines do not include cryoablation to treat other primary tumors that have metastasized to the lung.

The American College of Chest Physicians (ACCP), in their 2012 consensus statement on the treatment of stage 1 NSCLC stated that cryoablation has limited efficacy compared to lobectomy (Donington, 2012)

The use of cryosurgical ablation has also been studied to treat metastatic disease to the lungs. At this time, the published literature includes case reports, case series and reviews. However, there is a paucity of comparative effectiveness data to determine if cryosurgical ablation of pulmonary metastases is as beneficial as the available alternatives.

The largest published peer-reviewed study currently addressing the use of cryoablation for the treatment of metastatic lung tumors was published by de Baere and colleagues in 2015. This prospective case series study involved 40 subjects with 60 treated metastatic lung tumors from a variety of primary origins. The most common origin was colorectal cancer (40%). Follow-up to 12 months was reported, involving 35 subjects (90%). At 12 months, the overall local tumor control, including stable disease, partial, and complete response, was seen in 49 of 52 metastases (94.2%) and 32 of 35 subjects (91.4%). Local failure was observed in 3 of 52 metastases (5.8%) at 6 and 12 months with increasing size of the ablation zone. Tumor diameter was not found to be a significant factor in the rate of tumor progression (p=0.41). Additional new treatments were administered to 15 of the 40 subjects (38%) including systemic treatment (chemotherapy: n=7 and immunotherapy: n=1) and other focal therapies for new metastatic disease (n=10), including six cryoablation procedures. One-year disease-specific survival and OS rates were 100% and 97.5% respectively. Pneumothorax requiring chest tube placement occurred in 9 of the 48 procedures (18.8%), and chest tubes were removed after 1 day (n=8) or 2 days (n=1). Common Terminology Criteria for Adverse Events (CTCAE) grade 3 adverse events within 30 days of the procedure occurred in 3 of 48 (6%) procedures including a delayed pneumothorax requiring pleurodesis, a thrombosis of a pre-existing hemodialysis access arterio-venous fistula requiring thrombectomy, and a non-cardiac chest pain which spontaneously resolved. No grade 4 or 5 procedure-related adverse events occurred. No procedural-related delayed adverse events were observed. While the safety and efficacy of cryoablation for NSCLC has not yet been shown to be equivalent or better that other available treatment options.

Soft Tissue Sarcoma

The evidence addressing the use of cryoablation for the treatment of soft tissue sarcoma is very limited. At this time, there are only two small case series studies listed in the National Library of Medicine’s PubMed database describing this treatment method (Menendez, 1999; Tappero, 1991). These studies involved 12 and 20 subjects each, respectively, and only followed subjects for short time frames. While the NCCN guideline for soft tissue sarcoma (V.2.2017) includes recommendations for cryoablation, they do not provide a substantive rationale to support this position, nor do they provide any citations. Thus, the use of cryoablation for soft tissue sarcoma has not been demonstrated to be equal to or better than alternative treatment options.

Definitions

Cryosurgical ablation (cryotherapy or cryoablation): A surgical procedure where cancerous or diseased cells are destroyed using extreme cold.

Solid tumors: Tumors that appear in body tissues other than blood, bone marrow, or the lymphatic system; examples include tumors of the liver, lung, or colon.

Tumor: An abnormal mass of tissue that results from excessive cell division that is uncontrolled and progressive, also called a neoplasm.

Unresectable: A property of a tumor that makes it unable to be removed surgically.

References

Peer Reviewed Publications:

  1. Aron M, Gill IS. Renal tumor ablation. Curr Opin Urol. 2005; 15(5):298-305.
  2. Atwell TD, Schmit GD, Boorjian SA, et al. Percutaneous ablation of renal masses measuring 3.0 cm and smaller: comparative local control and complications after radiofrequency ablation and cryoablation. AJR Am J Roentgenol. 2013; 200(2):461-466.
  3. Aus G, Pileblad E, Hugosson J. Cryosurgical ablation of the prostate: 5-year follow-up of a prospective study. Eur Urol. 2002; 42(2):133-138.
  4. Bhayani SB, Belani JS, Hidalgo J, et al. Trends in nephron-sparing surgery for renal neoplasia. Urology. 2006; 68(4):732-736.
  5. Breen DJ, Bryant TJ, Abbas A, et al. Percutaneous cryoablation of renal tumours: outcomes from 171 tumours in 147 patients. BJU Int. 2013; 112(6):758-765.
  6. Buy X, Lang H, Garnon J, et al. Percutaneous renal cryoablation: prospective experience treating 120 consecutive tumors. AJR Am J Roentgenol. 2013; 201(6):1353-1361.
  7. Callstrom MR, Dupuy DE, Solomon SB, et al. Percutaneous image-guided cryoablation of painful metastases involving bone: Multicenter trial. Cancer. 2013; 119(5):1033-1041.
  8. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009; 182(4):1271-1279.
  9. Caputo PA, Ramirez D, Zargar H, et al. Laparoscopic cryoablation for renal cell carcinoma: 100-month oncologic outcomes. J Urol. 2015; 194(4):892-896.
  10. Cestari A, Guazzoni G, dell’Acqua V, et al. Laparoscopic cryoablation of solid renal masses: intermediate term followup. J Urol. 2004; 172(4 Pt 1):1267-1270.
  11. Chin JL, Al-Zahrani AA, Autran-Gomez AM, et al. Extended followup oncologic outcome of randomized trial between Cryoablation and external beam therapy for locally advanced prostate cancer (T2c-T3b). J Urol. 2012; 188(4):1170-1175.
  12. Davol PE, Fulmer BR, Rukstalis DB. Long-term results of cryoablation for renal cancer and complex renal masses. Urology. 2006; 68(1 Suppl):2-6.
  13. Deane LA, Clayman RV. Review of minimally invasive renal therapies: needle-based and extracorporeal. Urology. 2006; 68(1 Suppl):26-37.
  14. de Baere T, Tselikas L, Woodrum D, et al. Evaluating cryoablation of metastatic lung tumors in patients - safety and efficacy: the ECLIPSE trial - interim analysis at 1-year. Cardiol Rev. 2015; 10(10):1468-1474.
  15. De la Taille A, Hayek O, Benson MC, et al. Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience. Urology. 2000; 55(1):79-84.
  16. Desai MM, Aron M, Gill IS. Laparoscopic partial nephrectomy versus laparoscopic cryoablation for the small renal tumor. Urology. 2005; 66(5 Suppl):23-28.
  17. Donnelly BJ, Saliken JC, Ernst DS, et al. Prospective trial of cryosurgical ablation of the prostate: five-year results. Urology. 2002; 60(4):645-649.
  18. Drachenberg DE. Treatment of prostate cancer: watchful waiting, radical prostatectomy, and cryoablation. Semin Surg Oncol. 2000; 18(1):37-44.
  19. Dumot JA, Vargo JJ 2nd, Falk GW, et al. An open-label, prospective trial of cryospray ablation for Barrett's esophagus high-grade dysplasia and early esophageal cancer in high-risk patients. Gastrointest Endosc. 2009; 70(4):635-644.
  20. Edwards MJ, Broadwater R, Tafra L, et al. Progressive adoption of cryoablative therapy for breast fibroadenoma in community practice. Am J Surg. 2004; 188(3):221-224.
  21. El Dib R, Touma NJ, Kapoor A. Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies. BJU Int. 2012; 110(4):510-516.
  22. Emara AM, Kommu SS, Hindley RG, Barber NJ. Robot-assisted partial nephrectomy vs laparoscopic cryoablation for the small renal mass: redefining the minimally invasive 'gold standard'. BJU Int. 2014; 113(1):92-99.
  23. Fergany A. Current status and advances in nephron-sparing surgery. Clin Genitourin Cancer. 2006; 5(1):26-33.
  24. Gage AA, Baust JG. Cryosurgery for tumors. J Am Coll Surg. 2007; 205(2):342-356.
  25. Georgiades CS, Hong K, Bizzell C, et al. Safety and efficacy of CT-guided percutaneous cryoablation for renal cell carcinoma. J Vasc Interv Radiol. 2008; 19(9):1302-1310.
  26. Gestaut MM, Cai W, Vyas S, et al. Low-dose-rate brachytherapy versus cryotherapy in low- and intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017; 98(1):101-107.
  27. Gill IS, Novick AC, Meraney AM, et al. Laparoscopic renal cryoablation in 32 patients. Urology. 2000; 56(5):748-753.
  28. Gill IS, Remer EM, Hasan WA, et al. Renal cryoablation: outcome at 3 years. J Urol. 2005; 173(6):1903-1907.
  29. Golatta M, Harcos A, Pavlista D, et al. Ultrasound-guided cryoablation of breast fibroadenoma: a pilot trial. Arch Gynecol Obstet. 2014; 291(6):1355-1360
  30. Hafron J, Kaouk JH. Ablative techniques for the management of kidney cancer. Nat Clin Pract Urol. 2007; 4(5):261-269.
  31. Hafron J, Kaouk JH. Cryosurgical ablation of renal cell carcinoma. Cancer Control. 2007; 14(3):211-217.
  32. Haramis G, Graversen JA, Mues AC, et al. Retrospective comparison of laparoscopic partial nephrectomy versus laparoscopic renal cryoablation for small (<3.5 cm) cortical renal masses. J Laparoendosc Adv Surg Tech A. 2012; 22(2):152-157.
  33. Hegarty NJ, Gill IS, Desai MM, et al. Probe-ablative nephron-sparing surgery: cryoablation versus radiofrequency ablation. Urology. 2006; 68(1 Suppl):7-13.
  34. Hruby G, Reisiger K, Venkatesh R, et al. Comparison of laparoscopic partial nephrectomy and laparoscopic cryoablation for renal hilar tumors. Urology. 2006; 67(1):50-54.
  35. Huston TL, Simmons RM. Ablative therapies for the treatment of malignant diseases of the breast. Am J Surg. 2005; 189(6):694-701.
  36. Johnson DB, Solomon SB, Su LM, et al. Defining the complications of cryoablation and radio frequency ablation of small renal tumors: a multi-institutional review. J Urol. 2004; 172(3):874-877.
  37. Kaouk JH, Aron M, Rewcastle JC, Gill IS. Cryotherapy: clinical end points and their experimental foundations. Urology. 2006; 68(1 Suppl):38-44.
  38. 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):344-350.
  39. Kaufman CS, Bachman B, Littrup PJ, et al. Office-based ultrasound-guided cryoablation of breast fibroadenomas. Am J Surg. 2002; 184(5):394-400.
  40. Kishida T. Renal cryoablation: still experimental? Int J Urol. 2006; 13(7):885.
  41. Koppie TM, Shinohara K, Grossfeld GD, et al. The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience. J Urol. 1999; 162(2):427-432.
  42. Korpan NN. A history of cryosurgery: its development and future. J Am Coll Surg. 2007; 204(2):314-324.
  43. Kovach SJ, Hendrickson RJ, Cappadona CR, et al. Cryoablation of unresectable pancreatic cancer. Surgery. 2002; 131(4):463-464.
  44. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer. 2008; 13(10):2671-2680.
  45. Lawatsch EJ, Langenstroer P, Byrd GF, et al. Intermediate results of laparoscopic cryoablation in 59 patients at the Medical College of Wisconsin. J Urol. 2006; 175(4):1225-1229.
  46. Littrup PJ, Freeman-Gibb L, Andea A, et al. Cryotherapy for breast fibroadenomas. Radiology. 2005; 234(1):63-72.
  47. Littrup PJ, Ahmed A, Aoun HD, et al. CT-guided percutaneous cryotherapy of renal masses. J Vasc Interv Radiol. 2007; 18(3):383-392.
  48. Littrup PJ, Jallad B, Chandiwala-Mody P, et al. Cryotherapy for breast cancer: a feasibility study without excision. J Vasc Interv Radiol. 2009; 20(10):1329-1341.
  49. Long JP, Bahn D, Lee F, et al. Five-year retrospective, multi-institutional pooled analysis of cancer-related outcomes after cryosurgical ablation of the prostate. Urology. 2001; 57(3):518-523.
  50. Lowry PS, Nakada SY. Renal cryotherapy: 2003 clinical status. Curr Opin Urol. 2003; 13(3):193-197.
  51. Meftah M, Schult P, Henshaw RM. Long-term results of intralesional curettage and cryosurgery for treatment of low-grade chondrosarcoma. J Bone Joint Surg Am. 2013; 95(15):1358-1364.
  52. Menendez LR, Tan MS, Kiyabu MT, Chawla SP. Cryosurgical ablation of soft tissue sarcomas: a phase I trial of feasibility and safety. Cancer. 1999; 86(1):50-57.
  53. Mohler DG, Chiu R, McCall DA, Avedian RS. Curettage and cryosurgery for low-grade cartilage tumors is associated with low recurrence and high function. Clin Orthop Relat Res. 2010; 468(10):2765-2773.
  54. Moon TD, Lee FT Jr, Hedican SP, et al. Laparoscopic cryoablation under sonographic guidance for the treatment of small renal tumors. J Endourol. 2004; 18(5):436-440.
  55. Moore W, Talati R, Bhattacharji P, Bilfinger T. Five-year survival after cryoablation of stage I non-small cell lung cancer in medically inoperable patients. J Vasc Interv Radiol. 2015; 26(3):312-319.
  56. Nadler RB, Kim SC, Rubenstein JN, et al. Laparoscopic renal cryosurgery: the Northwestern experience. J Urol. 2003; 170(4 Pt 1):1121-1125.
  57. Nurko J, Mabry CD, Whitworth P, et al. Interim results from the Fibro Adenoma Cryoablation Treatment Registry. Am J Surg. 2005; 190(4):647-651.
  58. Oakley NE, Hagarty NJ, McNeill A, Gill IS. Minimally invasive nephron-sparing surgery for renal cell cancer. BJU Int. 2006; 98(2):278-284.
  59. O’Malley RL, Berger AD, Kanofsky JA, et al. A matched-cohort comparison of laparoscopic cryoablation and laparoscopic partial nephrectomy for treating renal masses. BJU Int. 2007; 99(2):395-398.
  60. Panumatrassamee K, Kaouk JH, Autorino R, et al. Cryoablation versus minimally invasive partial nephrectomy for small renal masses in the solitary kidney: impact of approach on functional outcomes. J Urol. 2013; 189(3):818-822.
  61. Permpongkosol S, Link RE, Kavoussi LR, Solomon SB. Percutaneous computerized tomography guided cryoablation for localized renal cell carcinoma: factors influencing success. J Urol. 2006; 176(5):1963-1968.
  62. Permpongkosol S, Nielsen ME, Solomon SB. Percutaneous renal cryoablation. Urology. 2006; 68(1 Suppl):19-25.
  63. Pfleiderer SO, Freesmeyer MG, Marx C, et al. Cryotherapy of breast cancer under ultrasound guidance: initial results and limitations. Eur Radiol. 2002; 12(12):3009-3014.
  64. Pusztaszeri M, Vlastos G, Kinkel K, Pelte MF. Histopathological study of breast cancer and normal breast tissue after magnetic resonance-guided cryotherapy ablation. Cryobiology. 2007; 55(1):44-51.
  65. Rivoire M, De Cian F, Meeus P, et al. Cryosurgery as a means to improve surgical treatment of patients with multiple unresectable liver metastases. Anticancer Res. 2000; 20(5C):3785-3790.
  66. Robinson D, Halperin N, Nevo Z. Two freezing cycles ensure interface sterilization by cryosurgery during bone tumor resection. Cryobiology. 2001; 43(1):4-10.
  67. Robinson JW, Donnelly BJ, Saliken JC, et al. Quality of life and sexuality of men with prostate cancer 3 years after cryosurgery. Urology. 2002; 60(2 Suppl 1):12-18.
  68. Rodriguez R, Chan DY, Bishoff JT, et al. Renal ablative cryosurgery in selected patients with peripheral renal masses. Urology. 2000; 55(1):25-30.
  69. Rukstalis DB, Khorsandi M, Garcia FU, et al. Clinical experience with open renal cryoablation. Urology. 2001; 57(1):34-39.
  70. Russo P. Renal cryoablation: study with care—proceed with caution. Urology. 2005; 65(3):419-421.
  71. Russo P. Renal cryoablation: a new treatment in need of careful clinical investigation. Nat Clin Pract Oncol. 2006; 3(6):286-287.
  72. 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):542-549.
  73. Schwartz BF, Rewcastle JC, Powell T, et al. Cryoablation of small peripheral renal masses: a retrospective analysis. Urology. 2006; 68(1 Suppl):14-18.
  74. Silverman SG, Tuncali K, van Sonnenberg E, et al. Renal tumors: MR imaging-guided percutaneous cryotherapy—initial experience in 23 patients. Radiology. 2005; 236(2):716-724.
  75. Simmons RM, Ballman KV, Cox C, et al.; ACOSOG investigators. A Phase II trial exploring the success of cryoablation therapy in the treatment of invasive breast carcinoma: results from ACOSOG (Alliance) Z1072. Ann Surg Oncol. 2016; 23(8):2438-2445.
  76. Tanagho YS, Bhayani SB, Kim EH, Figenshau RS. Renal cryoablation versus robot-assisted partial nephrectomy: Washington University long-term experience. J Endourol. 2013; 27(12):1477-1486.
  77. Tappero JW, Berger TG, Kaplan LD, et al. Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. J Acquir Immune Defic Syndr. 1991; 4(9):839-846.
  78. van der Geest IC, de Valk MH, de Rooy JW, et al. Oncological and functional results of cryosurgical therapy of enchondromas and chondrosarcomas grade 1. J Surg Oncol. 2008; 98(6):421-426.
  79. Van Poppel H, Becker F, Cadeddu JA, et al. Treatment of localised renal cell carcinoma. Eur Urol. 2011; 60(4):662-672.
  80. Warlick CA, Lima GC, Allaf ME, et al. Clinical sequelae of radiographic iceball involvement of collecting system during computed tomography-guided percutaneous renal tumor cryoablation. Urology. 2006; 67(5):918-922.
  81. Weld KJ, Figenshau RS, Venkatesh R, et al. Laparoscopic cryoablation for small renal masses: three-year follow-up. Urology. 2007; 69(3):448-451.
  82. Weld KJ, Landman J. Comparison of cryoablation, radiofrequency ablation and high-intensity focused ultrasound for treating small renal tumours. BJU Int. 2005; 96(9):1224-1229.
  83. Whitworth PW, Rewcastle JC. Cryoablation and cryolocalization in the management of breast disease. J Surg Oncol. 2005; 90(1):1-9.
  84. Zargar H, Samarasekera D, Khalifeh A, et al. Laparoscopic vs percutaneous cryoablation for the small renal mass: 15-year experience at a single center. Urology. 2015; 85(4):850-855.
  85. Zhao Z, Wu F. Minimally-invasive thermal ablation of early-stage breast cancer: a systemic review. Eur J Surg Oncol. 2010; 36(12):1149-1155.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Society of Breast Surgeons. Use of transcutaneous and percutaneous methods for the treatment of benign and malignant tumors of the breast. May 15, 2017. Available at: https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Transcutaneous_Percutaneous.pdf. Accessed on September 15, 2017.
  2. American Urological Association. Ablation of renal masses. 2013. Available at: http://www.auanet.org/guidelines/renal-masses-ablation-of. Accessed on September 15, 2017.
  3. American Urological Association. Clinically localized prostate cancer: AUA/ASTRO/SUO Guideline. 2017. Available at: http://www.auanet.org/guidelines/clinically-localized-prostate-cancer-new-(aua/astro/suo-guideline-2017). Accessed September 15, 2017.
  4. American Urological Association. Renal mass and localized renal cancer: AUA guideline. 2017 Available at: http://www.auanet.org/guidelines/renal-mass-and-localized-renal-cancer-new-(2017). Accessed on September 15, 2017.
  5. Campbell SC, Novick AC, Belldegrun A, et al.; Practice Guidelines Committee of the American Urological Association. Guideline for management of the clinical T1 renal mass. J Urol. 2009; 182(4):1271-1279.
  6. Centers for Medicare and Medicaid Services. National Coverage Determination for Cryosurgery of Prostate. NCD #230.9. Effective July 1, 2001. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd#PC. Accessed on September 15, 2017.
  7. Donington J, Ferguson M, Mazzone P, et al.; Thoracic Oncology Network of American College of Chest Physicians; Workforce on Evidence-Based Surgery of Society of Thoracic Surgeons. American College of Chest Physicians and Society of Thoracic Surgeons consensus statement for evaluation and management for high-risk patients with stage I non-small cell lung cancer. Chest. 2012; 142(6):1620-1635.
  8. NCCN Clinical Practice Guidelines in Oncology®: 2016 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on August 31, 2016.
    • Adult Cancer Pain (V.2.2017). Revised May 10, 2017
    • Basal Cell Skin Cancer V.1.2017. Revised October 3, 2016.
    • Bone Cancer (V.1.2018). Revised August 29, 2017.
    • Breast Cancer (V.2.2016). Revised May 6, 2016.
    • Esophageal and Esophagogastric Junction Cancers (V.2.2017). Revised August 7, 2017.
    • Kidney Cancer (V.1.2018). Revised September 7, 2017.
    • Non-Small Cell Lung Cancer. (V.8.2017). Revised July 14, 2017.
    • Pancreatic Adenocarcinoma (V.3.2017). Revised September 11, 2017.
    • Prostate Cancer (V.2.2017). Revised February 21, 2017.
    • Soft Tissue Sarcoma (V.2.2017). February 8, 2017.
  9. Wilt TJ, Shamliyan T, Taylor B, et al. Comparative effectiveness of therapies for clinically localized prostate cancer. Comparative effectiveness review No. 13. (Prepared by Minnesota Evidence-based Practice Center under Contract No. 290-02-0009). Rockville, MD: Agency for Healthcare Research and Quality. February 2008. Available at: https://www.ncbi.nlm.nih.gov/books/NBK43147/. Accessed on September 15, 2017.
Websites for Additional Information
  1. American Cancer Society. Available at: http://www.cancer.org. Accessed on September 15, 2017.
  2. National Cancer Institute. Cancer Facts. Cryosurgery in Cancer Treatment: Questions and Answers. September 10, 2003. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/cryosurgery. Accessed on September 15, 2017.
Index

Cryoablation
Cryosurgery
Cryosurgical Ablation

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development. Moved content of SURG.00025 Cryosurgical Ablation of Solid Tumors Outside the Liver to new clinical utilization management guideline document with the same title.  Updated Rationale section.  Updated Coding section with 01/01/2018 CPT changes; removed 0340T deleted 12/31/2017.