Medical Policies - Surgery


Radiofrequency Ablation (RFA) of Solid Tumors, Excluding Liver

Number:SUR701.021

Effective Date:07-01-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Osteolytic Bone Metastases

Radiofrequency ablation (RFA) may be considered medically necessary to treat osteolytic bone metastases in patients who have failed or are poor candidates for standard treatment such as surgical intervention, radiation, chemotherapy, or opioids.

Osteoid Osteomas

RFA may be considered medically necessary to treat osteoid osteomas that cannot be managed successfully with medical treatment.

Renal Cell Carcinoma (RCC)

RFA may be considered medically necessary to treat localized RCC that is no more than 4 cm in size when either of the following criteria is met:

When it is necessary to preserve kidney function in patients with significantly impaired renal function (i.e., the patient has 1 kidney or renal insufficiency defined by a glomerular filtration rate of <60 mL/min/m2) and when the standard surgical approach (i.e., resection of renal tissue) is likely to worsen existing kidney function substantially; or

When the patient is not considered a surgical candidate.

Non-Small-Cell Lung Cancer (NSCLC) Primary Pulmonary Tumor(s)

RFA may be considered medically necessary to treat an isolated peripheral NSCLC (primary pulmonary) lesion(s) that are no more than 3 cm in size when the following criteria are met:

When surgical resection or radiotherapy with curative intent is considered appropriate based on stage of disease, however, medical comorbidity renders the patient unfit for those interventions; and

When the tumor is located at least 1 cm from the trachea, main bronchi, esophagus, aorta, aortic arch branches, pulmonary artery, and the heart.

Malignant Non-Pulmonary Tumor(s) Metastatic to the Lung

RFA may be considered medically necessary to treat malignant non-pulmonary tumor(s) metastatic to the lung that are no more than 3 cm in size when the following criteria are met (see NOTE 1 below for additional considerations when using RFA to treat metastatic tumors to the lung):

When it is necessary to preserve lung function because surgical resection or radiotherapy is likely to worsen pulmonary status substantially OR when the patient is not considered a surgical candidate; and

When there is no evidence of extrapulmonary metastases; and

When the tumor is located at least 1 cm from the trachea, main bronchi, esophagus, aorta, aortic arch branches, pulmonary artery, and the heart.

NOTE 1: Additional considerations when using RFA to treat metastatic tumors to the lung:

No more than 3 tumors per lung should be ablated;

Tumors should be amenable to complete ablation; and

Twelve months should elapse before a repeat ablation is considered.

Miscellaneous Solid Tumors

RFA is considered experimental, investigational and/or unproven as a technique for ablation of:

Painful bone metastases as initial treatment;

Osteoid osteomas that can be managed with medical treatment;

RCC not meeting the criteria above;

Lung cancer not meeting the criteria above; and

All other tumors outside the liver including, but not limited to, the breast, head and neck, thyroid, pancreas, adrenal gland, ovary, and pelvic/abdominal metastases of unspecified origin.

NOTE 2: See medical policy SUR709.029 for Radiofrequency Ablation (RFA) of Primary or Metastatic Liver Tumors.

Description:

In radiofrequency ablation (RFA), a probe is inserted into the center of a tumor; then, prong-shaped, non-insulated electrodes are projected into the tumor. Next, heat is generated locally by an alternating, high-frequency current that travels through the electrodes. The localized heat treats the tissue adjacent to the probe, resulting in a 3- to 5.5-cm (centimeter) sphere of dead tissue. The cells killed by RFA are not removed but are gradually replaced by fibrosis and scar tissue. If there is local recurrence, it occurs at the edge and can sometimes be retreated. RFA may be performed percutaneously, laparoscopically, or as an open procedure.

Background

RFA was developed to treat various tumors, including inoperable tumors. For some of these, RFA is being investigated as an alternative to surgery for operable tumors. Well-established local or systemic treatment alternatives are available for each of these malignancies. The hypothesized advantages of RFA for these cancers include improved local control and those common to any minimally invasive procedure (e.g., preserving normal organ tissue, decreasing morbidity, decreasing length of hospitalization).

Goals of RFA may include:

1. Controlling local tumor growth and preventing recurrence;

2. Palliating symptoms; and

3. Extending survival duration for patients with certain tumors.

The effective volume of RFA depends on the frequency and duration of applied current, local tissue characteristics, and probe configuration (e.g., single versus multiple tips). When RFA is performed, the procedure is accompanied with ultrasound or computed tomography (CT) guidance.

Potential complications associated with RFA include those caused by heat damage to normal tissue adjacent to the tumor (e.g., intestinal damage during RFA of kidney), structural damage along the probe track (e.g., pneumothorax as a consequence of procedures on the lung), and secondary tumors (if cells seed spread during probe removal).

Osteolytic Bone Metastases

After lung and liver, bone is the third most common metastatic site and is relatively frequent among patients with primary malignancies of the breast, prostate, and lung. Bone metastases often cause osteolysis (bone breakdown), resulting in pain, fractures, decreased mobility, and reduced quality of life.

Treatment

External-beam radiotherapy often is the initial palliative therapy for osteolytic bone metastases. However, pain from bone metastases is refractory to radiotherapy in 20% to 30% of patients, while recurrent pain at previously irradiated sites may be ineligible for additional radiation due to risks of normal tissue damage. Other alternatives include hormonal therapy, radiopharmaceuticals (e.g., strontium 89), and bisphosphonates. Less often, surgery or chemotherapy may be used for palliation, and intractable pain may require opioid medications. RFA has been investigated as an alternative for palliation of bone metastases.

Osteoid Osteomas

Osteomas are the most common benign bone tumor, comprising 10% to 20% of benign and 2% to 3% of all bone tumors. They are typically seen in children and young adults, with most diagnosed in patients between 5 and 20 years of age. Osteomas are most common in the lower extremity (usually the long bones, mainly the femur) and less common in the spine. These tumors typically have a characteristic clinical presentation and radiologic appearance, with pain, usually continuous and worse at night, and usually relieved by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). The natural history of the osteoid osteoma varies based on location, and although they rarely exceed 1.5 cm in diameter, may produce bone widening and deformation, limb length inequality, or angular deviations when near a growth plate. When located in the spine, these lesions may lead to painful scoliosis or torticollis. Most osteoid osteomas will disappear or heal spontaneously after 3 to 7 years.

Treatment

Initial treatment options include medical management with NSAIDs to provide pain relief as the tumor gradually disappears on their own. When medical management fails, surgical excision (wide/en bloc excision or curetting) or the use of CT- or magnetic resonance imaging (MRI)?guided minimally invasive procedures including core drill excision, laser photocoagulation, or RFA may become an option for some patients. For many years, complete surgical excision was the classic treatment of osteomas, usually performed in patients with pain, despite medical management. However, a substantial incision may be necessary, with the removal of a considerable amount of bone (especially in the neck of the femur). This increases the need for bone grafting plus internal fixation (which often necessitates a second procedure to remove the metal work). Other possible risks include avascular necrosis of the femoral head and postoperative pathologic fracture. In addition, surgical excision leads to a lengthier convalescence and postoperative immobilization. Anatomically inaccessible tumors may not be completely resectable and may recur. RFA of osteoid osteoma is done with a needle puncture, so no incision or sutures are needed; further, patients may immediately walk on the treated extremity and return to daily activities when the anesthetic effect wears off. The risk of recurrence with RFA of an osteoma is 5% to 10%, and recurrent tumors can be retreated with RFA. In general, RFA is not performed in many spinal osteomas because of possible thermal-related nerve damage.

Renal Cell Carcinoma (RCC)

Radical nephrectomy remains the principal treatment of localized RCC; however, partial nephrectomy or nephron-sparing surgery has been shown to be as effective as radical nephrectomy, with comparable long-term recurrence-free survival rates, in a select group of patients. Alternative therapy such as RFA is of interest in patients with small renal tumors when preservation of renal function is necessary (e.g., in patients with marginal renal function, a solitary kidney, bilateral tumors) and in patients with comorbidities that would render them unfit for surgery. Another consideration would be in patients at high risk of developing additional renal cancers (e.g., von Hippel-Lindau disease).

Primary Pulmonary and Non-Pulmonary Tumors

Surgery is the current treatment of choice in patients with stage I primary non-small-cell lung cancer (NSCLC; stage I includes Ia [T1N0M0; refer to NOTE 3 below for TNM explanation] and 1b [T2N0M0]). Approximately 20% of patients present with stage I disease, although this number is expected to increase as a result of screening programs, advances in imaging modalities and widespread use of CT scans for other indications. Postsurgical recurrence rates of stage I NSCLC have been reported as between 20% and 30%, with most occurring at distant sites; locoregional recurrences occur in approximately 12%. Large differences in survival outcome are observed after surgery in stage 1 patients, with 5-year overall survival (OS) rates ranging from 77% for small T1 tumors to 35% for large T2 tumors. Untreated, stage I NSCLC has a 5-year overall survival rate range from 6% to 14%.

NOTE 3: The TNM is a classification system that describes the stage of a cancer which originates from a solid tumor with alphanumeric codes.

T describes the size of the original (primary) tumor and whether it has invaded nearby tissue,

N describes nearby (regional) lymph nodes that are involved,

M describes distant metastasis (spread of cancer from one part of the body to another).

Patients with early-stage NSCLC who are not surgical candidates may be candidates for radiotherapy with curative intent. In the 2 largest retrospective radiotherapy series, patients with inoperable disease treated with definitive radiotherapy achieved 5-year survival rates of 10% and 27%. In both studies, patients with T1N0 tumors had better 5-year survival rates of 60% and 32%, respectively.

Stereotactic body radiotherapy (SBRT) has gained more widespread use because it is a high-precision mode of therapy that delivers very high doses of radiation. Two- to 3-year local control rates of stage I NSCLC with SBRT have ranged from 80% to 95%. SBRT has been investigated in patients unfit to undergo surgery, with survival rates similar to surgical outcomes.

RFA also is being investigated in patients with small primary lung cancers or lung metastases who are deemed medically inoperable.

Miscellaneous Solid Tumors

RFA has been investigated for use in individuals with a number of different lesions in different anatomic sites. This includes, but is not limited to, breast, head and neck, and thyroid tumors.

Breast Tumors

The treatment of small cancers of the breast has evolved from total mastectomy to more conservative treatment options such as lumpectomy, with more acceptable cosmetic outcomes and preservation of the breast. The selection of surgical approach balances the patient’s desire for breast conservation and the need for tumor-free margins in resected tissue. Minimally invasive nonsurgical techniques such as RFA are appealing if they can produce local control and survival equivalent to breast-conserving surgical alternatives. Nonsurgical ablative techniques pose difficulties such as the inability to determine tumor size, complete tumor cell death, and local recurrence. Additionally, RFA can burn the skin and damage the muscle, possibly limiting use in patients with tumors near the skin or chest wall.

Head and Neck Cancer

In patients with head and neck cancer with recurrent disease, surgical salvage attempts are poor in terms of local control, survival, and quality of life; further, these recurrent tumors are often untreatable with standard salvage therapies. Palliative chemotherapy or comfort measures may be offered. The safety and efficacy of RFA has been investigated as an option for palliative treatment in these situations.

Thyroid Tumors

Surgical resection is the primary treatment choice for medically unresponsive, symptomatic benign thyroid tumors and thyroid carcinomas. However, techniques for ablation of thyroid tumors (e.g., RFA, microwave ablation) are being investigated.

Regulatory Status

The U.S. Food and Drug Administration (FDA) issued a statement in September 2008, concerning the regulatory status of RFA. FDA has cleared RFA devices for the general indication of soft tissue cutting, coagulation, and ablation by thermal coagulation necrosis. Under this general indication, RFA can be used to ablate tumors, including lung tumors. Some RFA devices have been cleared for additional specific treatment indications, including partial or complete ablation of nonresectable liver lesions and palliation of pain associated with metastatic lesions involving bone. The FDA has not cleared any RFA devices for the specific treatment indication of partial or complete ablation of lung tumors, citing lack of sufficient clinical data to establish safety and effectiveness for this purpose. The FDA has received reports of death and serious injuries associated with the use of RFA devices in the treatment of lung tumors.

Rationale:

This medical policy was originally created in 2007 and was regularly updated with searches of the MedLine database. The most recent literature review was performed through April 26, 2018. The following is a summary of key findings to date.

Assessment of efficacy for therapeutic intervention involves a determination of whether the intervention improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes, but are prone to biases such as noncomparability of treatment groups, placebo effect, and variable natural history of the condition.

Bone Tumors

Osteolytic Bone Metastases

Goetz et al. (2004) reported on an international study (n=43) conducted at 9 centers in which patients with painful osteolytic bone metastases were treated palliatively with radiofrequency ablation (RFA). (1) The study’s primary outcome measure was the Brief Pain Inventory?Short Form, a validated scale from 0 (no pain) to 10 (worst pain imaginable). Patient eligibility required baseline values of 4 or more from 2 or fewer painful sites. Thirty-nine (91%) of the patients had previously received opioids to control pain from the lesion(s) treated with RFA, and 32 (74%) had prior radiotherapy to the same lesion. The mean pain score at baseline was 7.9 (range, 4-10). At 4, 12, and 24 weeks after RFA, average pain scores decreased to 4.5, 3.0, and 1.4, respectively (all p<0.001). Forty-one (95%) patients achieved a clinically significant improvement in pain scores, prospectively defined as a decrease of 2 units from baseline. Investigators also reported statistically significant (p=0.01) decreases in opioid use at weeks 8 (by 59%) and 12 (by 54%).

An earlier case series (2002) showed that palliative RFA provided significant pain relief in 9 (90%) of 10 patients with unresectable, osteolytic spine metastases who had no other treatment options. (2) Pain was reduced by an average of 74%; back pain-related disability was reduced by an average of 27%. Neurologic function was preserved in 9 patients and improved in the other. An additional small case series (2006) of 24 patients with painful metastatic bone tumors who experienced pain-alleviating effects with RFA is consistent with other evidence. (3)

Section Summary: Osteolytic Bone Metastases

Case series have shown clinically significant pain relief and reduction in opioid use following treatment with RFA of osteolytic pain metastases in patients with no or limited treatment options.

Osteoid Osteomas

Systematic Reviews

Lanza et al. reported on a systematic review of various ablative techniques for osteoid osteomas in 2014. (4) Included in the review were 23 articles on RFA, 3 on interstitial laser ablation, and 1 with a combination of ablation techniques, totaling 27 articles (total n=1772 patients). The mean technical success was 100% and clinical success, defined as being pain-free, ranged from 94% to 98%, depending on length of follow-up. Complications occurred in 2% of patients and included skin or muscle burn in 9 patients, 4 infections, nerve lesions or tool breakage in 3 patients each, delayed skin healing, hematoma, and failure to reach target temperature in 2 patients each, and fracture, pulmonary aspiration, thrombophlebitis, and cardiac arrest in 1 patient each. Eighty-six patients had tumor recurrence.

Longer Term Follow-Up

An observational study published in 2015 evaluated long-term clinical outcomes after computed tomography (CT)?guided RFA in patients diagnosed with osteoid osteoma located in the upper and lower extremities. (5) The study population included 52 patients with a typical clinical history and radiologically confirmed osteoid osteoma who received CT-guided RFA treatment from 1998 to February 2014 at a Danish university hospital. The clinical outcome was evaluated based on patient-reported outcome measures and medical record review. The response rate was 52 (87%) of 60. After 1 RFA treatment, 46 (88%) of 52 patients experienced pain relief, and 51 (98%) of 52 patients had pain relief after repeat RFA. One patient underwent open resection after RFA. No major complications were reported; 4 patients reported minor complications including small skin burn, minor skin infection, and hypoesthesia at needle entry point. In all, 50 (96%) of 52 patients were reported to be "very satisfied" with the RFA treatment.

In 2012, Rimondi et al. reported on a retrospective study of 557 patients treated with CT-guided RFA as primary treatment for non-spinal osteoid osteomas. (6) All patients were followed for a mean of 3.5 years (range, 0.5-9 years). Pain relief occurred in all 557 patients within the first week after RFA and continued in 533 (96%) patients who remained asymptomatic through their last follow-up. Pain recurrence occurred in 24 (4%) patients. Complications occurred in 5 patients and included thrombophlebitis, skin burn, broken electrode, and 2 procedures in which the RFA generator failed to reach maximum temperature.

Rosenthal et al. (2003) reported their experience over an 11-year period with 271 RFA procedures for osteoid osteomas in 263 patients. (7) Short-term outcome was evaluated to detect procedure-related problems; by this definition, all procedures were considered technically successful. Long-term clinical success data (defined as being free of pain without the necessity of additional procedures) were available in 126 patients, with a complete clinical success observed in 89%. For procedures performed as the initial treatment, the success rate was 91%.

Section Summary: Osteoid Osteomas

Numerous case series and a systematic review of case series have evaluated RFA for the treatment of painful osteoid osteomas. In a systematic review of thermal ablation techniques, clinical success (pain-free) was achieved in 94% to 98% of patients. Most patients (89%-96%) remained pain-free at longer term follow-up.

Renal Cell Carcinoma (RCC)

Systematic Reviews

In a 2014 systematic review and meta-analysis, Katsanos et al. reviewed 1 RCT and 5 cohort studies (total n=587 patients) assessing thermal ablation (RFA or microwave) or nephrectomy for small renal tumors with a mean size of 2.5 cm. (8) The local recurrence rate was 3.6% in both groups (relative risk [RR], 0.92; 95% confidence interval [CI], 0.4 to 2.14; p=0.79). Disease-free survival was also similar in both groups up to 5 years (hazard ratio [HR], 1.04; 95% CI, 0.48 to 2.24; p=0.92). However, the overall complication rate was significantly lower in the patients undergoing ablation (7.4%) versus nephrectomy (11.1%; pooled RR=0.55; 95% CI, 0.31 to 0.97; p=0.04).

In another 2014 systematic review and meta-analysis, Wang et al. reported on studies evaluating RFA and partial nephrectomy for stage I (no more than 7 cm across) renal tumors. (9) Reviewers selected 166 studies (total n=9565 patients). The rate of local progression was greater with RFA than with laparoscopic/robotic or open partial nephrectomy (4.6%, 1.2%, 1.9%, respectively; p<0.001). RFA had more frequent minor complications than laparoscopic/robotic or open partial nephrectomy (13.8%, 7.5%, 9.5%, respectively; p<0.001). However, the rate of major complications was greater with open partial nephrectomy than laparoscopic/robotic partial nephrectomy or RFA (7.9%, 7.9%, 3.1%, respectively, p<0.001).

In 2012, El Dib et al. conducted a meta-analysis evaluating RFA and cryoablation for small renal masses. (10) Selected were 11 RFA case series (426 patients) and 20 cryoablation case series (457 patients) published through January 2011. The mean tumor size was 2.7 cm (centimeter; range, 2-4.3 cm) in the RFA group and 2.5 cm (range, 2-4.2 cm) in the cryoablation group. Mean follow-up times for the RFA and cryoablation groups were 18.1 and 17.9 months, respectively. Clinical efficacy, defined as cancer-specific survival rate, radiographic success, no evidence of local tumor progression, or distant metastases, did not differ significantly between groups. The pooled proportion of clinical efficacy for RFA was 90% (95% CI, 86% to 93%) and 89% (95% CI, 83% to 94%) for cryoablation.

Kunkle and Uzzo (2008) conducted a comparative meta-analysis evaluating cryoablation and RFA as primary treatments for small renal masses. (11) Forty-seven case series representing 1375 renal tumors were analyzed. Of 600 lesions treated with cryoablation, 494 underwent biopsy before treatment and 482 of 775 treated with RFA. The incidence of renal cell carcinoma with known pathology was 71.7% in the cryoablation group and 90% in the RFA group. The mean duration of follow-up after RFA was 15.8 months. Local tumor progression was reported in 31 of 600 lesions after cryoablation and in 100 of 775 lesions after RFA, a difference that was statistically significant (p<0.001). Progression to metastatic disease was described in 6 (1%) of 600 lesions after cryoablation vs 19 (3%) of 775 after RFA (p=0.06).

Longer Term Follow-Up

Stern et al. (2007) retrospectively compared patients with stage T1a renal tumors, confirmed by pathology to be RCC, treated with partial nephrectomy (n=34) or RFA (n=34). (12) The mean follow-up for the partial nephrectomy group was 47 months (range, 24-93 months) and 30 months (range, 18-42 months) for the RFA group. The 3-year recurrence-free survival rate was 95.2% for partial nephrectomy and 91.4% for RFA (p=0.58). There were no disease-specific deaths in either group. In this small study, intermediate outcomes for patients with T1a RCCs were similar whether treated with partial nephrectomy or RFA.

A 2016 publication by Iannuccilli et al. reported a mean 34.1-month follow-up (range, 1-131 months) of RFA with intent to cure in 203 patients with renal tumors. (13) Patients who were referred for RFA were either high risk or had refused surgery. Smaller tumors were treated with a single electrode with a 2- or 3-cm active tip. Larger tumors were treated with a cluster electrode with 3 active tips. Patients were assessed annually for appearance of residual tumor at the treatment site, and 26 (13%) had residual disease. Treatment effectiveness was 87% during follow-up. The likelihood was increased for tumors 3.5 cm or larger, clear cell subtype, and treatment temperature of 70° or less. All-cause mortality increased with increasing tumor size. The median survival was 7 years for patients with tumors less than 4 cm, with 80% survival at 5 years. Major complications, including urinary stricture or urine leak, occurred in 8 (3.9%) treatments.

Section Summary: RCC

The evidence on RFA for renal tumors includes meta-analyses of an RCT, cohort studies, and case series that have compared RFA with nephrectomy or cryoablation. A 2014 meta-analysis that included 1 RCT and 5 cohort studies found that RFA was as effective as nephrectomy for small renal tumors, with a reduction in complications. Another 2014 meta-analysis, which included case series of stage I (no more than 7 cm across) renal tumors, found that the rate of local progression was greater with RFA than with nephrectomy, but the rate of major complications was lower with RFA. The conflicting results between these meta-analyses might be due to differences in tumor sizes in selected studies as well as selection bias when comparing case series. The correlation between tumor size and RFA efficacy has been reinforced by a large case series with a mean 34-month follow-up; it found that residual disease and mortality increased with tumors over 4 cm.

Primary Pulmonary Tumors and Non-Pulmonary Tumors

Non-Small-Cell Lung Cancer (NSCLC)/Primary Pulmonary Tumor(s)

Systematic Reviews

In 2013, the Agency for Healthcare Research and Quality (AHRQ) published A Comparative Effectiveness Review on Local Nonsurgical Therapies for stage I Non-Small-Cell Lung Cancer (NSCLC). (14) In this review, no comparative RFA studies were identified. The Agency report found that available evidence was insufficient to draw conclusions on the comparative effectiveness of local nonsurgical therapies for NSCLC, including RFA.

In a 2014 systematic review of RFA, surgery, and stereotactic body radiotherapy (SBRT) for colorectal cancer (CRC) lung metastases, no randomized trials were identified, and evidence was insufficient to draw conclusions on the comparative effectiveness of these therapies. (15)

In a 2012 review of 16 studies, Bilal et al. compared RFA with SBRT in patients with inoperable early-stage NSCLC. (16) Reviewers found that overall survival (OS) rates for RFA and SBRT were similar in patients at 1 year (68.2%-95% versus 81%-85.7%) and 3 years (36%-87.5% versus 42.7%-56%), all respectively. However, survival rates at 5 years were lower with RFA (20.1%-27%) than with SBRT (47%). These findings were drawn from comparisons of results of uncontrolled case series and retrospective reviews.

In a 2011 evidence-based review, 46 studies on RFA for lung tumors were evaluated, which included 2905 ablations in 1584 patients with a mean tumor size of 2.8 cm. (17) Twenty-four studies reported rates of local recurrence, which occurred in 282 (12.2%) cases at a mean follow-up time of 13 months (range, 3-45 months). Primary lung cancer rates of local recurrence did not differ significantly (22.2%) from metastases (18.1%). Twenty-one studies reported mean OS rates of 59.4% at a mean follow-up time of 17.7 months. The mean cancer-specific survival rate was 82.6%, at a mean follow-up of 17.4 months. The mean overall morbidity was 24.6% and most commonly included pneumothorax (28.3%), pleural effusion (14.8%), and pain (14.1%). Mortality related to the RFA procedure was 0.21%, overall.

Comparative Studies

In 2010, Zemlyak et al. prospectively compared 3 treatments for medically inoperable patients with stage I NSCLC: RFA in 12 patients, sublobar resection in 25 patients, and percutaneous cryoablation in 27 patients. (18) At 3-year follow-up, survival rates did not differ significantly between groups. OS and cancer-specific 3-year survival rates were 87.5%, 87.1%, and 77% and 87.5%, 90.6%, and 90.2%, respectively, in the 3 groups. The authors concluded that all 3 procedures were reasonable options for treatment of lung tumors in patients unfit for major surgery. The authors also noted that because surgeons chose the treatment option with patient input for this study, selection bias limited study interpretation.

In 2011, Huang et al. prospectively followed 329 consecutive patients treated with RFA for lung tumors (237 primary, 92 metastatic). (19) Complications were experienced by 34.3% (113) of patients, most commonly pneumothorax (19.1%). OS rates at 2 and 5 years were 35.3% and 20.1%, respectively. The risk of local progression did not differ significantly for tumors less than 4 cm but were statistically significant for tumors greater than 4 cm.

Inoperable Lung Tumors/Non-Pulmonary Tumor(s)

Clinical Trials

A prospective, single-arm, multicenter trial (2008) from 7 centers in Europe, the U.S., and Australia reported the technical success, safety, response of tumors, and survival in 106 patients with 183 lung tumors. (20) All patients were considered unsuitable for surgery and unfit for radiotherapy or chemotherapy. Tumors measured less than 3.5 cm (mean, 1.7 cm; SD=1.3) and included patients with NSCLC (n=22), colorectal metastases (n=41), and other metastases (n=16). Technical success rate was 99%. Patients were followed for 2 years, and a confirmed complete response lasting at least 1 year was observed in 88% of assessable patients, with no differences in response rate between patients with primary and metastatic tumors. OS rates in patients with NSCLC were 70% at 1 year (95% CI, 51% to 83%; cancer-specific survival, 92% [78% to 98%]), and 48% at 2 years (95% CI, 30% to 65%; cancer-specific survival, 73% [54% to 86%]). OS rates in patients with metastatic CRC were 89% at 1 year (95% CI, 76% to 95%; cancer-specific survival, 91% [78% to 96%]) and 66% at 2 years (95% CI, 53% to 79%; cancer-specific survival 68% [54% to 80%]). OS rates in patients with other metastases were 92% at 1 year (95% CI, 65% to 99%; cancer-specific survival, 93% [67% to 99%]) and 64% at 2 years (95% CI, 43% to 82%; cancer-specific survival, 67% [48% to 84%]). Patients with stage I NSCLC (n=13) had an OS rate of 75% (95% CI, 45% to 92%) at 2 years (cancer-specific, 92%; 95% CI, 66% to 99%). No differences in response were seen between patients with NSCLC or lung metastases.

Zhu et al. (2009) assessed the incidence and risk factors of various pulmonary neoplastic complications after RFA. (21) They prospectively evaluated the clinical and treatment-related data for 129 consecutive percutaneous RFA treatment sessions for 100 patients with inoperable lung tumors. There was no postprocedural mortality. The overall morbidity rate was 43% (55/129). The most common adverse effect was pneumothorax, occurring in 32% (41/129) of treatment sessions. Other significant complications included pleuritic chest pain (18%), hemoptysis (7%), pleural effusions (12%), and chest drain insertion (20%). Both univariate and multivariate analyses identified more than 2 lesions ablated per session as a significant risk factor for overall morbidity, pneumothorax, and chest drain insertion. The length of the ablation probe trajectory greater than 3 cm was an additional independent risk factor for overall morbidity and pneumothorax.

In 2009, Pennathur et al. reported on 100 patients with inoperable lung tumors. (22) Forty-six patients had primary lung neoplasm, 25 had recurrent cancer, and 29 had pulmonary metastases. The mean follow-up was 17 months. Median OS for all patients was 23 months. The probability of 2-year OS for primary lung cancer patients, recurrent cancer patients, and metastatic cancer patients were 50% (95% CI, 33% to 65%), 55% (95% CI, 25% to 77%), and 41% (95% CI, 19% to 62%), respectively.

Section Summary: Primary Pulmonary and Non-Pulmonary Tumors

The evidence on RFA for primary NSCLC and non-pulmonary tumor metastatic to the lung includes prospective and retrospective case series of patients with inoperable lung tumors with over 100 patients and systematic reviews of those studies. No RCTs identified compared treatment approaches. For inoperable lung tumors, a multicenter study found that RFA for tumors less than 3.5 cm can lead to a complete response in as many as 88% of patients for at least 1 year. Two-year survival has been reported to range from 41% to 75% in case series. Survival at 1 and 2 years appears to be similar, following treatment with RFA or stereotactic ablative radiotherapy in patients with inoperable lung tumors. Survival rates at 5 years were lower with RFA (20.1%-27%) than with stereotactic ablative radiotherapy (47%), but this finding was drawn from comparisons of uncontrolled case series and retrospective reviews. Prospective comparison in an RCT would permit greater certainty for this finding, but the studies are consistent with some effect of RFA on lung tumors.

Miscellaneous Solid Tumors

Breast Tumors

Systematic Reviews

In 2010, Zhao and Wu conducted a systematic review of 38 studies on ablation techniques for breast cancer treatment published from 1994 to 2009. (23) Nine studies focused on RFA. Reviewers included small breast tumors ranging in size from 0.5 to 7 cm. Tumor resection was performed immediately after ablation or up to 4 weeks after RFA. Complete coagulation necrosis rates of 76% to 100% were reported. The results suggested RFA for breast cancer tumors is feasible, but further studies with longer follow-up on survival, tumor recurrence, and cosmetic outcomes are needed to establish clinical efficacy.

In another 2010 review, Soukup et al. examined 17 studies on RFA for the treatment of breast tumors and found RFA is feasible and promising. (24) Even though few adverse events and complications occurred with breast RFA, incomplete tumor ablation remains a concern.

Clinical Studies

In 2012, Wilson et al. reported on 73 patients with invasive breast cancer who had a lumpectomy followed immediately by RFA to the lumpectomy bed. (25) The average breast tumor size was 1.0 cm (range, 0.2-2.6 cm) and follow-up averaged 51 months. Disease-free survival was 100%, 92%, and 86% at 1, 3, and 5 years, respectively. One patient had tumor recurrence within 5 cm of the lumpectomy site, and 3 patients had ipsilateral breast recurrences.

In a 2011 phase 1/2 study, 49 patients were treated with RFA for breast tumors (mean size, 1.70 cm) followed immediately with surgical resection. (26) Complete ablation was achieved in 30 (61%) patients as assessed by hematoxylin-eosin (H&E) staining and/or nicotinamide adenine dinucleotide (NADH) diaphorase staining. Complete ablation increased to 83% in 24 patients with tumor sizes of 2 cm or less in diameter. Adverse events related to the procedure included 3 muscle and 2 skin burns.

In 2009, Imoto et al. reported on a series of 30 patients with T1N0 breast cancer who had sentinel node biopsy followed by RFA and breast-conserving surgery. (27) Twenty-six patients showed pathologic degenerative changes in tumor specimens with H&E staining, and, in 24 of 26 cases, tumor cell viability was diagnosed as negative by NADH diaphorase staining. Two patients had skin burns, and seven had muscle burn related to RFA.

In a 2008 2-stage phase 2 clinical trial, patients with histologically confirmed noninflammatory and 3 cm or less ipsilateral breast tumor recurrence were treated with RFA followed by mastectomy. (28) The study was ended early due to lack of efficacy of the technique tested.

Section Summary: Breast Tumors

Systematic reviews and observational studies have reported varied and incomplete ablation rates as well as concerns about post-ablation tumor cell viability. Long-term improvements in health outcomes have not been demonstrated. Additionally, available studies have not compared RFA with conventional breast-conserving procedures. For small breast tumors, further study, with long-term follow-up, is needed to determine whether RFA can provide local control and survival rates comparable with conventional breast-conserving treatment.

Thyroid Tumors

Systematic Reviews

In 2014 Fuller et al. reported on a systematic review of studies on RFA for benign thyroid tumors. (29) Selected were 9 studies (5 observational studies, 4 randomized studies), totaling 306 treatments. After RFA, statistically significant improvements were reported in nodule size reduction (29.77 mL; 95% CI, -13.83 to -5.72 mL), combined symptom improvement and cosmetic scores on the 0 to 6 scale (mean, -2.96; 95% CI, -2.66 to -3.25), and withdrawal from methimazole (odds ratio, 40.34; 95% CI, 7.78 to 209.09). Twelve adverse events were reported, 2 of which were considered significant but did not require hospitalization. The interpretation of the meta-analysis is limited by the variability in the comparator arms (percutaneous ethanol injection, percutaneous laser ablation and, high-intensity focused ultrasound ablation. The only RCT included in the meta-analysis had a small sample size of 30.

In 2012, the Korean Society of Thyroid Radiology developed consensus recommendations for RFA of thyroid tumors after a review of the literature found few controlled studies. (30) The recommendations indicated RFA might be appropriate for the treatment of benign thyroid nodules, inoperable thyroid nodules, and recurrent thyroid cancers in the operation bed and lymph nodes. The Society’s recommendations also indicated RFA should not be used for primary thyroid cancers or follicular neoplasms, citing no evidence of treatment benefit.

Clinical Studies

In 2013, Lim et al. reported on a case series of 111 patients treated with RFA for 126 benign nonfunctioning thyroid nodules. (31) The mean duration of patient follow-up was 49.4 months. RFA significantly decreased the volume of the thyroid nodules from 9.8±8.5 mL to 0.9±3.3 mL (p<0.001), for a mean volume decrease of 93.4%. Tumors recurred in 7 (5.6%) patients. Complications occurred in 4 (3.6%) patients. There was also a significant improvement in thyroid symptom scores (p<0.001).

Baek et al. (2012) retrospectively reviewed RFA for 1543 benign thyroid nodules in 1459 patients at 13 thyroid centers. (32) Forty-eight (3.3%) complications occurred and included 20 major complications: voice changes (n=15), brachial plexus injury (n=1), tumor rupture (n=3), and permanent hypothyroidism (n=1). Twenty-eight minor complications included: hematoma (n=15), skin burn (n=4), and vomiting (n=9).

A 2009 case series of 94 elderly subjects with solid or mainly solid benign thyroid nodules was reported by an Italian center. (33) Thyroid nodule volume, compressive symptoms, and thyroid function were evaluated at baseline and 12 to 24 months post-treatment. All thyroid nodules significantly decreased in size after RFA. Compressive symptoms improved in all patients, disappearing completely in 88% of patients. Hyperthyroidism resolved in most patients, permitting complete withdrawal of methimazole therapy in 79% of patients with pretoxic and toxic thyroid nodules (100% with pretoxic and 53% with toxic thyroid nodules).

Section Summary: Benign Thyroid Tumors

Evidence on the treatment of benign thyroid nodules includes randomized trials, case series, and systematic reviews of these studies. A systematic review that included 1 RCT, 3 randomized studies, and 5 observational studies found significant reductions in nodule size and withdrawal from methimazole following treatment with RFA. Reports of complications vary. The most frequent major complication from a large multicenter series was voice changes. However, the comparators were variable and nonconventional. The single RCT had a small sample size of 30.

Thyroid Cancer

In 2016, Kim et al. reported on a comparative review of 73 patients with recurrent thyroid cancer smaller than 2 cm who had been treated with RFA (n=27) or repeat surgery (n=46). (34) RFA was performed in cases of patient refusal to undergo surgery or poor medical condition. Data were weighted to minimize potential confounders. The 3-year recurrence-free survival rates were similar for RFA (92.6%) and surgery (92.2%, p=0.681). Post-treatment hoarseness rate did not differ between the RFA (7.3%) and surgery (9.0%) groups. Post-treatment hypocalcemia occurred only in the surgery group (11.6%).

Section Summary: Thyroid Cancer

Evidence on the treatment of thyroid cancer is scant with 1 comparative review of RFA and repeat surgery. Outcomes were similar for both types of treatments. Further study is warranted to evaluate complications, particularly hoarseness rates and hypocalcemia before determination if RFA can local control and survival rates compared to conventional surgical procedures.

Head and Neck Cancer

In 2011, Owen et al. reported on RFA for 13 patients with recurrent and/or unresectable head and neck cancer who failed curative treatment. (35) Median patient survival was 127 days. While stable disease was reported in 8 patients after RFA, and quality of life scores improved, 3 deaths occurred (1 carotid hemorrhage, 2 strokes).

A case series of RFA for 14 patients with recurrent advanced head and neck malignancies was reported by Brook et al. (2008). (36) Tumor targeting and electrode deployment was successful in all cases, and 4 of 6 patients who completed quality of life assessments showed improvement. Three major complications (in 27 [11%] applications) occurred 7 days to 2 weeks post-procedure. They included stroke, carotid artery rupture leading to death, and threatened carotid artery rupture with subsequent stroke. Retrospective analysis of intraprocedural CT scans revealed that the retractable electrodes were within 1 cm of the carotid artery during ablation in these cases.

A 2004 case series showed palliative CT-guided RFA provided subjective improvement with regard to pain, appearance, and function in 12 patients who had recurrent and advanced head and neck malignancies and were not candidates for radiotherapy or surgery. (37) The procedure appeared reasonably safe and feasible for this indication.

Section Summary: Head and Neck Cancer

Three case series, totaling 31 patients, provided patient outcomes/complications with head and neck cancers treated with RFA. Complications reported were hemorrhage, strokes, with some leading to death. Palliative pain relief, appearance, and function were also assessed in 1 of the 3 studies. Further study is warranted to evaluate the outcomes/complicates before RFA is accepted as a viable treatment for head and neck cancers.

Other Miscellaneous Tumors

A large 2015 series evaluated the effectiveness and safety of RFA for uterine myomas in a 10-year retrospective cohort study. (38) From 2001 to 2011, a total of 1216 patients treated for uterine myomas were divided into 2 groups. Group A consisted of 476 premenopausal patients (average age, 36 years) who had an average of 1.7 myomas with an average diameter of 4.5 cm. Group B consisted of 740 menopausal patients (average age, 48 years) with an average of 2.6 myomas with an average diameter of 5.0±2.5 cm. Patients were followed for a mean of 36 months. At 1, 3, 6, 12, and 24 months after RFA, the average diameters of myomas in group A were 3.8, 3.0, 2.7, 2.4, and 2.2 cm, respectively; 48% (227/476) of patients had residual tumor at 12 months. In group B, myoma diameters were 4.7, 3.7, 3.3, 2.3, and 2.3 cm, respectively; 59% (435/740) of patients had trace disease at 12 months. Three months after RFA treatment, myoma volumes were significantly reduced in both the groups (p<0.01), although group B had a higher rate of residual tumor 12 months after RFA than group A (p<0.05). Clinical symptoms and health-related quality of life were significantly improved after RFA in both groups. The postoperative recurrence rate of uterine myomas was significantly higher in group A at 10.7% (51/476) than in group B at 2.4% (18/740; p<0.05).

One 2004 case series of 13 patients with adrenal neoplasms treated with RFA was identified. In this study, 11 of the 13 lesions were treated successfully with RFA, defined by follow-up CT scans and normalization of preprocedural biochemical abnormalities. (39)

A single-arm, retrospective, paired-comparison study (2004) evaluated the short-term efficacy of RFA in relation to pain and functional impact in patients with unresectable, painful soft tissue neoplasms recalcitrant to conventional therapies. (40) Patients had tumors located in a variety of sites including chest wall, pelvis, breast, perirectal, renal, aortocaval, retroperitoneal, and superficial soft tissues. All had failed conventional methods of palliation or experienced dose-limiting adverse events from pain medication. Although not all Brief Pain Inventory scores were statistically significant, all mean scores trended down with increased time after ablation. Complications from RFA were minor or insignificant in all but 1 patient who had skin breakdown and infection of an ablated superficial tumor site.

Additional research has addressed the use of RFA in solid malignancies (41, 42) and in the pancreas. (43-45) A 2015 systematic review has examined studies of ablative therapies, including RFA, in patients with locally advanced pancreatic cancer. (46) No RCTs were identified, and conclusions limited by the sparse evidence available on RFA in this setting.

Stereotactic radiofrequency thermocoagulation for epileptogenic hypothalamic hamartomas was described in a 2009 retrospective analysis of 25 patients with gelastic seizures (a rare type of seizure). (47) Other seizure types were exhibited in 22 (88.0%) patients, precocious puberty in 8 (32.0%), behavioral disorder in 10 (40.0%), and mental disability in 14 (56.0%). Gelastic seizures resolved in all but 2 patients. Complete seizure freedom was achieved in 19 (76.0%) patients. These patients experienced resolution of all seizure types and behavioral disorder and also demonstrated intellectual improvement.

Preliminary results of endoscopic RFA of rectosigmoid tumors have been described by Vavra et al. (2009). (48) Twelve patients were treated with the Endoblate RFA device, with 10 patients having surgical resection after ablation. Histology of the resected specimens showed that, on average, 82% (range, 60%-99%) of the tumor mass was destroyed in the ablation zone.

Small case series on RFA for colorectal and rectal carcinoma have demonstrated a debulking role for RFA. (49, 50) These case series did not permit comparison with an available alternative.

Section Summary: Other Miscellaneous Tumors

Evidence on the use of RFA to treat other types of solid tumors consists of a low number of case series or retrospective comparative studies for each tumor type. Reporting on outcomes is limited. The evidence base does not support conclusion on the effects of RFA.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT Number

Trial Name

Planned

Enrollment Completion Date

Ongoing

NCT01051037

Phase II Study Evaluating Safety and Efficacy of Stereotactic Body Radiotherapy and RFA for Medically Inoperable and Recurrent Lung Tumors Near Central Airways.

35

August 2017 (ongoing)

Unpublished

NCT00776399

RFA in Resectable Colorectal Lung Metastasis: A Phase-II Clinical Trial

70

August 2017

(completed)

Table Key:

NCT: national clinical trial;

RFA: Radiofrequency ablation (RFA)

Clinical Input From Physician Specialty Societies and Academic Medical Centers

In 2010 the Blue Cross Blue Shield Association (BCBSA) obtained input from 2 physician specialty societies (4 reviewers) and 2 academic medical centers (4 reviewers). Support for the use of RFA in lung tumors was less than it was in 2009 (only 1 respondent indicated this was an option in tumors metastatic to lung). One respondent also indicated potential use for adrenal tumors. Comments on the specific role for RFA in renal tumors were again mixed.

In 2009 the Blue Cross Blue Shield Association (BCBSA) obtained input from 1 physician specialty society (4 reviews) and from 2 academic medical centers (3 reviews) while this policy was under review for February 2009. All reviewers supported the use of RFA in the treatment of painful bone metastases that have failed standard treatment and in the treatment of osteoid osteomas. The reviewers were divided with regards to the use of RFA for lung tumors, although several agreed that while it may be useful in a select population of patients, it should be used in the setting of a clinical trial. The reviewers were also split with regards to RFA in the treatment of renal tumors, with some supporting its use in a select population of patients. With the exception of 1 disagreement and 1 nonresponse, the reviewers agreed to the investigational statement regarding the use of RFA in all other tumors outside the liver that are addressed in this policy.

Practice Guidelines and Position Statements

American College of Chest Physicians (ACCP)

The ACCP guidelines (2013) on the treatment of stage I and II NSCLC have indicated RFA has been used effectively in clinical stage I NSCLC. (51) Therefore, in medically inoperable patients, peripheral NSCLC tumors less than 3 cm may be treated with RFA. The College also collaborated with the Society of Thoracic Surgeons (STS) to develop consensus guidelines on the treatment of high-risk patients with stage I NSCLC. (52) These 2012 consensus guidelines indicated RFA is an alternative treatment option in patients who are not surgical candidates due to severe medical comorbidity.

National Comprehensive Cancer Network (NCCN)

The NCCN practice guidelines for the treatment of NSCLC (v.4.2018) state, “Resection is the preferred local treatment modality (other modalities include radiofrequency ablation, cryotherapy and SABR [stereotactic ablative radiotherapy]).” (53)

The NCCN guidelines for thyroid carcinoma (v.2.2017) indicate that local therapies such as RFA may be considered for locoregional recurrence of thyroid carcinoma-papillary carcinoma. (54)

The NCCN guidelines for kidney cancer (v.4.2018) indicate that ablative techniques such as RFA “can be considered for selected patients with clinical stage T1 renal disease.” (55) The guidelines note that ablative techniques are associated with higher rates of local recurrence than traditional surgery.

Current NCCN guidelines do not address the utilization/management of RFA for the following indications:

Breast cancer (v.1.2018), (56)

Head and neck cancer (v.1.2018), (57)

Colon (colorectal) cancer (v.2.2018), (58) and

Bone cancer (v.2.2018). (59)

National Institute for Clinical Excellence (NICE)

The NICE guidance (2004) for osteoid osteoma indicated that “current evidence on the safety and efficacy of computed tomography (CT)-guided thermocoagulation of osteoid osteoma appears adequate to support its use…” (60)

The NICE guidance (2010) for renal cancer indicated that “evidence on the safety and efficacy of percutaneous radiofrequency ablation (RFA) for renal cancer in the short and medium term appears adequate to support the use of this procedure provided that patients are followed up in the long term.” (61)

The NICE guidance (2010) for primary and secondary lung cancers stated that “[C]urrent evidence on the efficacy of percutaneous radiofrequency ablation (RFA) for primary or secondary lung cancers is adequate in terms of tumor control.” (62) NICE also indicated RFA might “be used in patients with small, early-stage lung cancers or small numbers of lung metastases who are unsuitable for, or prefer not to undergo, surgery. It may also have a place in multi-modality treatment of more advanced primary lung cancers.” The guidance warned of serious complications (e.g., pneumothorax) among lung cancer patients.

The NICE guidance (2016) for benign thyroid nodules stated that “Current evidence on the safety and efficacy of ultrasound?guided percutaneous radiofrequency ablation for benign thyroid nodules is adequate to support the use of this procedure….” (63)

Summary of Evidence

Osteolytic Bone Metastases

For individuals who have painful osteolytic bone metastases who have failed or are poor candidates for standard treatments who receive radiofrequency ablation (RFA), the evidence includes case series. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. Case series have shown clinically significant pain relief and reduction in opioid use following treatment of painful osteolytic metastases. The population is comprised of patients with few or no treatment options, for whom short-term pain relief is an appropriate clinical outcome. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Osteoid Osteomas

For individuals who have painful osteoid osteomas who receive RFA, the evidence includes numerous observational studies and a systematic review of these studies. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. In a systematic review of thermal ablation techniques, clinical success (pain-free) was achieved in 94% to 98% of patients. Most patients (89%-96%) remained pain-free when assessed during longer term follow-up. Although no randomized trials of RFA for osteoid osteomas have been performed, the uncontrolled studies have demonstrated RFA can provide adequate symptom relief with minimal complications, for a population for whom short-term symptom relief and avoidance of invasive procedures are appropriate clinical outcomes. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Renal Cell Carcinoma

For individuals who have localized renal cell carcinoma (RCC) that is no more than 4 cm in size who receive RFA, the evidence includes a randomized controlled trial (RCT), a large number of observational studies, and systematic reviews of these studies. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related morbidity. A recent meta-analysis that included only an RCT and cohort studies found that RFA was as effective as nephrectomy for small renal tumors, with a reduction in complications. Another recent meta-analysis, which included case series of stage I (≤7 cm across) renal tumors, found that the rate of local progression was greater with RFA than with nephrectomy. The differing meta-analytic results may be due to differences in tumor size in selected studies as well as potential selection bias when evaluating case series. Although inconsistent, the evidence does suggest that, for small renal tumors, RFA may result in a similar rate of disease progression with a lower complication rate than nephrectomy. However, comparative trials are needed to determine with greater certainty the effects of these treatments in the same patient population. The evidence is insufficient to determine the effects of the technology on health outcomes.

Primary Pulmonary Tumor(s) or Malignant Non-Pulmonary Tumor(s) Metastatic to the Lung

For individuals who have primary pulmonary tumors or non-pulmonary tumors metastatic to the lung who receive RFA, the evidence includes observational studies and systematic reviews of these studies. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related morbidity. A multicenter study found that, for tumors less than 3.5 cm in size, RFA can lead to a complete response in as many as 88% of patients for at least 1 year. Two-year survival rates have been reported to range from 41% to 75% in case series, with 5-year survival rates of 20% to 27%. In general, the evidence suggests that RFA results in adequate survival and tumor control in patients who are not surgical candidates, with low morbidity rates. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Miscellaneous Solid Tumors

Breast Tumors

For individuals who have breast tumors who receive RFA, the evidence includes observational studies and systematic reviews of these studies. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related morbidity. Evidence has reported varied and incomplete ablation rates with concerns about post-ablation tumor cell viability. Long-term improvements in health outcomes have not been demonstrated. Additionally, available studies do not permit comparisons with conventional breast-conserving procedures. Further studies, with long-term follow-up, should focus on whether RFA of the breast for small tumors can provide local control and survival rates comparable with conventional breast-conserving treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.

Thyroid Tumors

For individuals who have benign thyroid tumors who receive RFA, the evidence includes RCTs, case series, and systematic reviews of these studies. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. A systematic review that included 4 RCTs and 5 observational studies found significant reductions in nodule size and withdrawal from methimazole following treatment with RFA when compared to a variety of local treatment. Reports of complications have varied. The most frequent major complication in a large multicenter series of specialty centers was voice change. The evidence is insufficient to determine the effects of the technology on health outcomes.

Other Miscellaneous Tumors

For individuals who have miscellaneous tumors (e.g., head and neck, thyroid cancer, pancreas, adrenal, soft tissue neoplasms, colorectal) who receive RFA, the evidence includes a few case series and retrospective comparative studies. Relevant outcomes are overall survival, change in disease status, quality of life, and treatment-related morbidity. There is a limited evidence base for each tumor type. Reporting on outcomes or comparisons with other treatments is limited. These studies do not permit conclusions on the health benefits of RFA. The evidence is insufficient to determine the impact of the technology on health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage versus non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

20982, 32998, 50541, 50542, 50592, 76940, 77013, 77022.

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Goetz MP, Callstrom MR, Charboneau JW, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol. Jan 15 2004; 22(2):300-6. PMID 14722039

2. Gronemeyer DH, Schirp S, Gevargez A. Image-guided radiofrequency ablation of spinal tumors: preliminary experience with an expandable array electrode. Cancer J. Jan-Feb 2002; 8(1):33-9. PMID 11898806

3. Kojima H, Tanigawa N, Kariya S, et al. Clinical assessment of percutaneous radiofrequency ablation for painful metastatic bone tumors. Cardiovasc Intervent Radiol. Nov-Dec 2006; 29(6):1022-6. PMID 16988875

4. Lanza E, Thouvenin Y, Viala P, et al. Osteoid osteoma treated by percutaneous thermal ablation: when do we fail? A systematic review and guidelines for future reporting. Cardiovasc Intervent Radiol. Dec 2014; 37(6):1530-9. PMID 24337349

5. Knudsen M, Riishede A, Lucke A, et al. Computed tomography-guided radiofrequency ablation is a safe and effective treatment of osteoid osteoma located outside the spine. Dan Med J. May 2015; 62(5). PMID 26050823

6. Rimondi E, Mavrogenis AF, Rossi G, et al. Radiofrequency ablation for non-spinal osteoid osteomas in 557 patients. Eur Radiol. Jan 2012; 22(1):181-8. PMID 21842430

7. Rosenthal DI, Hornicek FJ, Torriani M, et al. Osteoid osteoma: percutaneous treatment with radiofrequency energy. Radiology. Oct 2003; 229(1):171-5. PMID 12944597

8. Katsanos K, Mailli L, Krokidis M, et al. Systematic review and meta-analysis of thermal ablation versus surgical nephrectomy for small renal tumours. Cardiovasc Intervent Radiol. Apr 2014; 37(2):427-37. PMID 24482030

9. Wang S, Qin C, Peng Z, et al. Radiofrequency ablation versus partial nephrectomy for the treatment of clinical stage 1 renal masses: a systematic review and meta-analysis. Chin Med J (Engl). Jul 2014; 127(13):2497-503. PMID 24985591

10. 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. Aug 2012; 110(4):510-516. PMID 22304329

11. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer. Nov 15 2008; 113(10):2671-80. PMID 18816624

12. Stern JM, Svatek R, Park S, et al. Intermediate comparison of partial nephrectomy and radiofrequency ablation for clinical T1a renal tumours. BJU Int. Aug 2007; 100(2):287-90. PMID 17617136

13. Iannuccilli JD, Dupuy DE, Beland MD, et al. Effectiveness and safety of computed tomography-guided radiofrequency ablation of renal cancer: a 14-year single institution experience in 203 patients. Eur Radiol. Jun 2016; 26(6):1656-64. PMID 26373755

14. Ratko TA, Vats V, Brock J, et al. Local Nonsurgical Therapies for Stage I and Symptomatic Obstructive Non- Small-Cell Lung Cancer (Comparative Effectiveness Review No. 112) (2013). Rockville, (MD): Agency for Healthcare Research and Quality. Available at <https://www.ahrq.gov> (accessed April 25, 2018).

15. Schlijper RC, Grutters JP, Houben R, et al. What to choose as radical local treatment for lung metastases from colo-rectal cancer: Surgery or radiofrequency ablation? Cancer Treat Rev. Jun 12 2013; 40(1):60-7. PMID 23768754

16. Bilal H, Mahmood S, Rajashanker B, et al. Is radiofrequency ablation more effective than stereotactic ablative radiotherapy in patients with early stage medically inoperable non-small cell lung cancer? Interact Cardiovasc Thorac Surg. Aug 2012; 15(2):258-65. PMID 22581864

17. Chan VO, McDermott S, Malone DE, et al. Percutaneous radiofrequency ablation of lung tumors: evaluation of the literature using evidence-based techniques. J Thorac Imag. Feb 2011; 26(1):18-26. PMID 20829720

18. Zemlyak A, Moore WH, Bilfinger TV. Comparison of survival after sublobar resections and ablative therapies for stage I non-small cell lung cancer. J Am Coll Surg. Jul 2010; 211(1):68-72. PMID 20610251

19. Huang L, Han Y, Zhao J, et al. Is radiofrequency thermal ablation a safe and effective procedure in the treatment of pulmonary malignancies? Eur J Cardiothorac Surg. Mar 2011; 39(3):348-51. PMID 20663679

20. Lencioni R, Crocetti L, Cioni R, et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol. Jul 2008; 9(7):621-8. PMID 18565793

21. Zhu JC, Yan TD, Glenn D, et al. Radiofrequency ablation of lung tumors: feasibility and safety. Ann Thorac Surg. Apr 2009; 87(4):1023-8. PMID 19324122

22. Pennathur A, Abbas G, Gooding WE, et al. Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients by a thoracic surgical service. Ann Thorac Surg. Nov 2009; 88(5):1601-6; discussion 1607-8. PMID 19853119

23. Zhao Z, Wu F. Minimally-invasive thermal ablation of early-stage breast cancer: a systemic review. Eur J Surg Oncol. Dec 2010; 36(12):1149-55. PMID 20889281

24. Soukup B, Bismohun S, Reefy S, et al. The evolving role of radiofrequency ablation therapy of breast lesions. Anticancer Res. Sep 2010; 30(9):3693-7. PMID 20944155

25. Wilson M, Korourian S, Boneti C, et al. Long-term results of excision followed by radiofrequency ablation as the sole means of local therapy for breast cancer. Ann Surg Oncol. Oct 2012; 19(10):3192-8. PMID 22911363

26. Kinoshita T, Iwamoto E, Tsuda H, et al. Radiofrequency ablation as local therapy for early breast carcinomas. Breast Cancer. Jan 2011; 18(1):10-7. PMID 20072824

27. Imoto S, Wada N, Sakemura N, et al. Feasibility study on radiofrequency ablation followed by partial mastectomy for stage I breast cancer patients. Breast. Apr 2009; 18(2):130-4. PMID 19324550

28. Garbay JR, Mathieu MC, Lamuraglia M, et al. Radiofrequency thermal ablation of breast cancer local recurrence: a phase II clinical trial. Ann Surg Oncol. Nov 2008; 15(11):3222-6. PMID 18709415

29. Fuller CW, Nguyen SA, Lohia S, et al. Radiofrequency ablation for treatment of benign thyroid nodules: systematic review. Laryngoscope. Jan 2014; 124(1):346-53. PMID 24122763.

30. Na DG, Lee JH, Jung SL, et al. Radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: consensus statement and recommendations. Korean J Radiol. Mar-Apr 2012; 13(2):117-25. PMID 22438678

31. Lim HK, Lee JH, Ha EJ, et al. Radiofrequency ablation of benign non-functioning thyroid nodules: 4-year follow-up results for 111 patients. Eur Radiol. Apr 2013; 23(4):1044-9. PMID 23096937

32. Baek JH, Lee JH, Sung JY, et al. Complications encountered in the treatment of benign thyroid nodules with US guided radiofrequency ablation: a multicenter study. Radiology. Jan 2012; 262(1):335-42. PMID 21998044

33. Spiezia S, Garberoglio R, Milone F, et al. Thyroid nodules and related symptoms are stably controlled two years after radiofrequency thermal ablation. Thyroid. Mar 2009; 19(3):219-25. PMID 19265492

34. Kim JH, Yoo WS, Park YJ, et al. Efficacy and safety of radiofrequency ablation for treatment of locally recurrent thyroid cancers smaller than 2 cm. Radiology. Sep 2015; 276(3):909-18. PMID 25848897

35. Owen RP, Khan SA, Negassa A, et al. Radiofrequency ablation of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg. May 2011; 137(5):493-8. PMID 21576561

36. Brook AL, Gold MM, Miller TS, et al. CT-guided radiofrequency ablation in the palliative treatment of recurrent advanced head and neck malignancies. J Vasc Interv Radiol. May 2008; 19(5):725-35. PMID 18440462

37. Owen RP, Silver CE, Ravikumar TS, et al. Techniques for radiofrequency ablation of head and neck tumors. Arch Otolaryngol Head Neck Surg. Jan 2004; 130(1):52-6. PMID 14732768

38. Yin G, Chen M, Yang S, et al. Treatment of uterine myomas by radiofrequency thermal ablation: a 10-year retrospective cohort study. Reprod Sci. May 2015; 22(5):609-14. PMID 25355802

39. Mayo-Smith WW, Dupuy DE. Adrenal neoplasms: CT-guided radiofrequency ablation--preliminary results. Radiology. Apr 2004; 231(1):225-30. PMID 14990812

40. Locklin JK, Mannes A, Berger A, et al. Palliation of soft tissue cancer pain with radiofrequency ablation. J Support Oncol. Sep-Oct 2004; 2(5):439-45. PMID 15524075

41. Rosenthal DI. Radiofrequency treatment. Orthop Clin North Am. Jul 2006; 37(3):475-84, viii. PMID 16846772

42. Liapi E, Geschwind JF. Transcatheter and ablative therapeutic approaches for solid malignancies. J Clin Oncol. Mar 10 2007; 25(8):978-86. PMID 17350947

43. Spiliotis JD, Datsis AC, Michalopoulos NV, et al. Radiofrequency ablation combined with palliative surgery may prolong survival of patients with advanced cancer of the pancreas. Langenbeck's Arch Surg. Jan 2007; 392(1):55-60. PMID 17089173

44. Zou YP, Li WM, Zheng F, et al. Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer. World J Gastroenterol. Oct 28 2010; 16(40):5104-10. PMID 20976848

45. Cantore M, Girelli R, Mambrini A, et al. Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma. Br J Surg. Aug 2012; 99(8):1083-8. PMID 22648697

46. Rombouts SJ, Vogel JA, van Santvoort HC, et al. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. Br J Surg. Feb 2015; 102(3):182-93. PMID 25524417

47. Kameyama S, Murakami H, Masuda H, et al. Minimally invasive magnetic resonance imaging-guided stereotactic radiofrequency thermocoagulation for epileptogenic hypothalamic hamartomas. Neurosurgery. Sep 2009; 65(3):438-49; discussion 449. PMID 19687687

48. Vavra P, Dostalik J, Zacharoulis D, et al. Endoscopic radiofrequency ablation in colorectal cancer: initial clinical results of a new bipolar radiofrequency ablation device. Dis Colon Rectum. Feb 2009; 52(2):355-8. PMID 19279436

49. Mylona S, Karagiannis G, Patsoura S, et al. Palliative treatment of rectal carcinoma recurrence using radiofrequency ablation. Cardiovascul Intervent Radiol. Aug 2012; 35(4):875-82. PMID 22167304

50. Ripley RT, Gajdos C, Reppert AE, et al. Sequential radiofrequency ablation and surgical debulking for unresectable colorectal carcinoma: thermo-surgical ablation. J Surg Oncol.
Feb 2013; 107(2):144-7. PMID 22927225

51. Howington JA, Blum MG, Chang AC, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. May 2013; 143(5 Suppl):e278S-313S. PMID 23649443

52. Donington J, Ferguson M, Mazzone P, et al. 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. Dec 2012; 142(6):1620-35. PMID 23208335

53. NCCN – Non-Small Cell Lung Cancer. V.4.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Available at <http://www.nccn.org> (accessed April 26, 2018).

54. NCCN – Thyroid Cancer V.2.2017. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Available at <http://www.nccn.org>. (accessed April 26, 2018).

55. NCCN – Kidney Cancer V.4.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Available at <http://www.nccn.org>. (accessed April 26, 2018).

56. NCCN – Breast Cancer V.1.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Available at <http://www.nccn.org>. (accessed April 26, 2018).

57. NCCN – Head and Neck Cancer V.1.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Available at <http://www.nccn.org>. (accessed April 26, 2018).

58. NCCN – Colon Cancer V.2.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Available at <http://www.nccn.org>. (accessed April 26, 2018).

59. NCCN – Bone Cancer V.2.2018. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Colon Cancer. Available at <http://www.nccn.org>. (accessed April 26, 2018).

60. NICE – Computed Tomography-Guided Thermocoagulation of Osteoid Osteoma (2004). National Institute for Clinical Excellence. Available at <http://www.nccn.org>. (accessed April 26, 2018).

61. NICE – Percutaneous Radiofrequency Ablation of Renal Cancer (2010). National Institute for Clinical Excellence. Available at <http://www.nccn.org> (accessed April 26, 2018).

62. NICE – Percutaneous Radiofrequency Ablation for Primary and Secondary Lung Cancers (2010). National Institute for Clinical Excellence. Available at <http://www.nccn.org> (accessed April 26, 2018).

63. NICE – Ultrasound-Guided Percutaneous Radiofrequency Ablation for Benign Thyroid Nodules (2016). National Institute for Health and Care Excellence. Available at <https://www.nice.org.uk> (accessed April 26, 2018).

64. Radiofrequency Ablation of Miscellaneous Solid Tumors Excluding Liver Tumors. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (September 2017) Surgery 7.01.95.

Policy History:

DateReason
7/1/2018 Document updated with literature review. Osteoid Osteomas or Bony Metastases split into 2 separate coverage statements: 1) Radiofrequency ablation (RFA) may be considered medically necessary to treat osteolytic bone metastases in patients who have failed or are a poor candidate for standard treatment such as surgical intervention, radiation, chemotherapy, or opioids; and 2) RFA may be considered medically necessary to treat osteoid osteomas that cannot be managed successfully with medical treatment. Numerous wording changes to coverage, but intent of coverage remained unchanged. The following NOTE was added: NOTE 2: See medical policy SUR709.029 for Radiofrequency Ablation (RFA) of Primary or Metastatic Liver Tumors. The following references have been added: 8, 13, 34, and 63; numerous references removed.
4/15/2017 Reviewed. No changes.
8/1/2016 Policy updated with literature review. The following changes were made to Coverage: 1) Removed “only when determined to be indicated by the treating physician” from the osteoid osteoma or bony metastases coverage criteria; 2) Removed “palliative treatment of medically or surgically inoperable tumor(s)” and added “that is no more than 4 cm in size” to the renal cell carcinoma coverage criteria; 3) Revised bullet from “patients who have failed, or are a poor candidate for standard treatment such as surgical intervention, radiation, chemotherapy and opioids” to now state “the patient is not considered a surgical candidate” in the renal cell carcinoma coverage criteria; 4) Removed “radiofrequency ablation may be considered medically necessary for treatment of primary and metastatic neoplasms when removal of the neoplasm may be curative but the patient has been determined by the treating physician to be unable to tolerate surgical resection.” 5) Removed “Primary and metastatic neoplasms when the patient has been determined by the treating physician to be able to tolerate surgical resection” from the EIU coverage section.
5/15/2015 Reviewed. No changes.
7/1/2014 Document updated with literature review. Coverage of osteomas, bony metastases, and inoperable tumors is unchanged. In addition, the following changes were made: 1) Coverage of renal cell carcinoma (RCC) was moved to this policy from SUR710.017 (Radiofrequency Ablation [RFA] and Cryoablation of Renal Cell Carcinoma [RCC]) and SUR710.017 was deleted; coverage of RCC is unchanged. 2) Coverage of pulmonary tumors was moved from SUR706.012 (Radiofrequency Ablation [RFA] of Pulmonary Tumors) and SUR706.012 was deleted; 3) New detailed coverage criteria were added for isolated peripheral non-small-cell lung cancer and for malignant nonpulmonary tumors metastatic to the lung.
6/1/2013 Document updated with literature review. Coverage unchanged. Rationale was revised.
7/1/2011 Document updated with literature review. Coverage unchanged.
8/15/2009 Revised/updated entire document with literature search. No change in coverage position.
6/1/2007 Revised/updated entire document
1/1/2007 New medical document

Archived Document(s):

Back to Top