National Medical Policy

National Medical Policy Subject: Policy Number: Radiofrequency Ablation for Renal Cell Cancer NMP213 Effective Date*: March 2005 Updated: August 2015 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate Medicaid Manuals for coverage guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link National Coverage Determination (NCD) National Coverage Manual Citation X Local Coverage Determination (LCD)* Ablative Therapy: http://www.cms.gov/medicare-coveragedatabase/search/advanced-search.aspx Article (Local)* Other None Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. Radiofrequency Ablation for Renal Cell Cancer Aug 15 1

If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Policy Statement Health Net, Inc. considers radiofrequency ablation (RFA) therapy of renal tumors, up to 4 cm in size, medically necessary in a select group of patients who meet any of the following criteria: 1. Patients with solitary kidney, or with comprised renal function; 2. Patients who are high risk for surgical resection due to poor clinical status; 3. Patients with compromised renal function in whom preservation of renal function is necessary. Definitions RFA Radiofrequency ablation SMR Small renal masses RCC Renal cell Carcinoma PFS Progression-free survival Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures will be replaced by ICD-10 code sets. Health Net National Medical Policies will now include the preliminary ICD-10 codes in preparation for this transition. Please note that these may not be the final versions of the codes and that will not be accepted for billing or payment purposes until the October 1, 2015 implementation date. ICD-9 Codes 189.0 Malignant neoplasm of kidney, except pelvis 233.9 Carcinoma in situ; other and unspecified urinary organs ICD-10 Codes C64.9 Malignant neoplasm of unspecified kidney, except renal pelvis D09.10 Carcinoma in situ of unspecified urinary organ D09.19 Carcinoma in situ of other urinary organs CPT Codes 50592 Ablation, one or more renal tumor(s), percutaneous, unilateral, radiofrequency. HCPCS Codes N/A Scientific Rationale Update August 2015 Pieper et al (2015) analyzed the outcome of patients undergoing percutaneous CTguided radiofrequency ablation (RFA) of small renal masses (SRM) at a single center Radiofrequency Ablation for Renal Cell Cancer Aug 15 2

during a ten-year time period. Patient records of renal RFAs (07/2003-11/2013) were reviewed. Indications were SRM suspicious of malignancy on imaging and one of the following: severe comorbidity; old age; solitary kidney; impaired renal function; patient wish. Biopsy was performed at the time of RFA. Patients were excluded if no follow-up was available. Patient and procedural characteristics were recorded. Survival rates were calculated using the Kaplan-Meier's method and compared with log-rank or cox tests. 38 patients (16 females, mean age 70.0 years [range 52-87]) presenting with a solitary SRM were included in the study. Biopsy showed malignancy in 29 patients; 9 had benign tumors. 26 patients suffered from cardiovascular, respiratory or hepatic comorbidities. Technical success (complete ablation on first follow-up) was achieved in 95% of cases. Two major complications (bowel perforation; hematothorax) occurred. The 3- and 7-year overall survival (OS) [any cause] rates were 73.4±0.8% and 50.3±1.0%, respectively (mean follow-up 54.6 months, range 1-127). 4 recurrences and 2 metastases were observed. The presence of comorbidities was the only independent predictor of OS. There was no difference in survival between patients with benign and malignant tumors. The authors concluded RFA of SRM is successful in a large percentage of cases with a low complication rate and durable local control. As RFA is typically performed in multimorbid patients, overall survival seems to depend primarily on comorbidities rather than cancer progression. Cooper et al (2015) reported renal cell carcinoma (RCC) accounts for 3% of all cancers in adults. The indications for RFA for renal carcinomas include T1a (tumor 4 cm or less, limited to the kidney), elderly patients, renal impairment, comorbidities, poor surgical candidate, and multiple bilateral renal masses. The authors retrospectively reviewed medical records, specifically investigating the indications, complications and outcomes of RFA and nephrectomy for treatment of RCC in a tertiary medical center with a predominantly Hispanic patient population. Forty-nine patients with RCC were evaluated. Nine patients had RFA, 9 had partial nephrectomy and 31 had radical nephrectomy. All patients among the 3 groups had stage T1N0M0 RCC at diagnosis. Tumor recurrence was observed in 2 (22%) patients that had RFA, one (11%) patient that had partial nephrectomy and no patients that had radical nephrectomy. One patient had recurrence of the tumor at the opposite kidney pole from the initial RFA site 4 years later. This particular patient did not have any tumor recurrence at the site of the initial RFA. A second RFA was performed on the recurrent tumor with no recurrence upon subsequent follow up visits. The second patient had recurrence of the RCC on 1 year follow that was discovered to be sarcomatoid RCC, which is an aggressive type with a poor prognosis. The reviewers concluded the results support the clinical utility of RFA in patients with stage T1 RCC who are poor surgical candidates or those with reduced renal function. The clinical utility of RFA as an equally effective approach when compared to partial nephrectomy in patients with stage T1 RCC that meet strict indications for the procedure. The treatment choice should be individualized and based on the characteristics of the renal tumor such as size, location and histological type of RCC. We conclude that RFA presents a safe treatment choice for patients with RCC if long term follow up is maintained. Chang et al (2015) compared outcomes in patients treated with RFA and partial nephrectomy (PN) for clinical T1a RCC in a propensity-score matched cohort. The authors conducted a retrospective review of the records of all patients who underwent RFA or nephrectomy between February 2005 and December 2009 in a single institution. The Kaplan-Meier method was used to generate the survival curves that were compared with the log-rank test. Univariable and multivariable regression Radiofrequency Ablation for Renal Cell Cancer Aug 15 3

analyses were performed to determine predictors of survival. A total of 90 patients were included in the final study after being matched by propensity scores (RFA 45; PN 45). The 5-year overall survival (95% confidence interval [CI]) was 90.2% (78.6-98.8) vs 93.2% (85.8-98.9); 5-year cancer-specific survival (95% CI) was 95.6% (89.5-98.1) vs 97.7% (93.4-99.3); 5-year disease-free survival (95% CI) was 86.7% (89.5-96.7) and 88.5% (79.1-97.9); 5-year recurrence-free survival (95% CI) was 95.4% (89.3-98.1) vs 97.7% (93.3-99.2); and 5-year metastasis-free survival (95% CI) was 95.5% (89.4-98.0) vs 95.5% (89.4-98.0). Age was the only factor that could predict the disease-free survival (P=0.044). The percentage decrease in the glomerular filtration rate was significantly lower in the RFA group at the time of last follow-up (P=0.001). The authors concluded in the propensity-score matched cohort of patients with clinical T1a RCC, we observed that RFA was an effective treatment option that provided comparable 5-year oncologic outcomes and better preservation of renal function than PN. Miller et al (2015) evaluated outcomes of percutaneous ablation of small renal tumors in the elderly population. Using their tumor ablation database, the authors searched for percutaneous ablation procedures for clinical T1a renal masses in octogenarians and nonagenarians between June 2001 and May 2012. Altogether, 105 tumors from 99 procedures among 95 patients (mean age 84.0±3.0 years, range 80-92) were identified. Oncologic outcomes and major complications were evaluated. Assessment also included patient hospital stays and renal functional outcomes. Technical success was achieved in 60/61 (98.4%) tumors managed with cryoablation and 43/44 (97.7%) after radiofrequency ablation (RFA). Of 87 renal tumors with at least 3 months imaging follow-up, 2 (5.4%) tumors progressed at 1.2 and 2.2 years after RFA. None recurred after cryoablation. Estimated progressionfree survival rates at 1, 3, and 5 years after ablation were 99%, 97%, and 97%, respectively. Thirty-four patients died at a mean of 3.7 years after ablation (median 3.7; range 0.4-9.6). Estimated overall survival rates were 98%, 83%, and 61%, respectively. Among 33 patients with sporadic, biopsy-proven renal-cell carcinoma, estimated cancer-specific survival rates were 100%, 100%, and 86%, respectively. Five (8.6%) major complications developed after renal cryoablation with no (0%) major complication after RFA. Mean decrease in serum creatinine level within 1 week after ablation was 0.1mg/dL. Mean hospitalization was 1.2 days. The authors concluded percutaneous thermal ablation is safe and effective in the active management of clinical T1a renal masses in elderly patients. Cheng et al (2014) investigated clinical outcomes of ultrasound-guided percutaneous radiofrequency ablation (USG-RFA) in patients with renal clear cell carcinoma. Medical records of 34 patients who underwent USG-RFA of renal clear cell carcinoma at a single center from May 2009 to January 2014 were retrospectively reviewed, including 28 male and 6 female patients aged between 25 and 85 years (mean age 60.7 years). Of the included cases, 16 had tumors located in the left kidney, 16 in the right, 1 in the solitary kidney, and 1 in the bilateral kidney. There were 35 tumors in this study totally. The maximum diameter of the tumors was 1.8 to 5.0 cm (mean (2.7 ± 0.3) cm), of which 32 cases of renal tumors were 4.0 cm and 3 cases of renal tumors were > 4.0 cm to 5.0 cm. Pathological diagnosis were acquired by ultrasound-guided percutaneous biopsy after USG-RFA. Contrast-enhanced ultrasound was used to evaluate tumor outcomes at the time of the surgery, and multi-slice spiral CT enhanced scan and contrast-enhanced ultrasound were used to identify residues and recurrences after treatment. Treatments for all the patients were finished with short postoperative hospital stay about 3-5 days. No complications related to USG-RFA were encountered in any of the cases, such as Radiofrequency Ablation for Renal Cell Cancer Aug 15 4

perirenal fluid collection, perirenal hematoma, and peripheral organ damage. All the cases were diagnosed as clear cell carcinoma according to pathological results. The mean follow-up period was 29 ± 6 (range 3-59) months. Of the 35 USG-RFA-treated subjects, 32 tumors 4 cm reached the standard of complete treatment after one tumor was found with residue after the first month follow-up, and two tumors were noted recurrence at the 4 and 10 months follow-up after USG-RFA. Nonetheless, no residue or recurrence occurred after secondary treatment for these 3 tumors where pathological diagnosis were acquired again. The other 3 cases with tumors > 4.0 cm to 5.0 cm underwent USG-RFA twice or three times before reaching the standard of complete treatment, of which two had twice and one tumor had three times treatments. There was no carcinoma residue or recurrence during follow-up period. The authors concluded percutaneous ultrasound-guided RFA for SRM has satisfied clinical outcomes, with the advantage of less injury, lower complication rates and shorter recovery time for small size of renal clear cell carcinoma. USG-RFA may become the preferred treatment alternative for SRM. Scientific Rationale Update August 2013 Per the NCCN guidelines on Kidney Cancer (2013), Principles of Surgery: Observation or ablative techniques (eg. cryosurgery, radiofrequency ablation): Can be considered for patients with clinical stage T1 renal lesions who are not surgical candidates Biopsy of surgical lesions may be considered to obtain or confirm a diagnosis of malignancy and guide surveillance, cryosurgery, and radiofrequency ablation strategies. Randomized phase III comparison with surgical resection (i.e., radical or partial nephrectomy by open or laparoscopic techniques) have not been done. Ablative techniques are associated with a higher local recurrence rate than conventional surgery. Tsimafeyeu et al (2013) evaluated the role of cytoreductive radiofrequency ablation (crfa) in patients with metastatic renal cell carcinoma (RCC) with small primary tumors treated with immuno- or targeted therapy. To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumors. Three parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumor <5cm; good or intermediate prognosis according to the Memorial Sloan-Kettering Cancer Center model; and no previous therapy. Study 1: Patients were treated with percutaneous crfa under computed tomography guidance followed by interferon (IFN)-α, 9 MIU, s.c., three times per week. Study 2: Patients received crfa followed by sunitinib in repeated 6-week cycles of 50mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression-free survival (PFS). Baseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumor size) were similar in all three studies. Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively. Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P < 0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 Radiofrequency Ablation for Renal Cell Cancer Aug 15 5

months (P = 0.02). The median (95% CI) objective survival (OS) times were greater in study 2 (crfa/sunitinib) and study 3 (sunitinib-alone) than in study 1 (IFN-α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the crfa/sunitinib group compared with the sunitinib-alone group (HR = 0.71; P = 0.04). There were no unexpected toxicities of medical treatment or complications of crfa. Investigators concluded crfa is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. The crfa technique did not improve PFS in patients treated with sunitinib; crfa probably has impact on OS in these patients. This needs to be tested in a larger trial. Sunitinib was effective in patients with metastatic RCC with unresected small primary tumors. Karam et al (2013) evaluated their experience with radiofrequency ablation (RFA) for renal masses and to report on clinical, radiological and post-rfa biopsy results. The study collected clinical, radiological and pathological data from 150 consecutive patients who were treated with RFA of a renal mass between 2002 and 2008 at a tertiary referral centre. Post-ablation biopsies were performed in patients with noninvoluting lesions or suspicion of recurrence on imaging. Comparisons were performed using the Mann-Whitney U-test. Survival was estimated using the Kaplan- Meier method. Renal malignancy was found in 72.1% of patients based on the initial diagnostic biopsy. Median tumor size was 2.6 cm, 22.7% of patients had a solitary kidney, and most were central tumors. The mean follow-up period was 40.1 month. There was no recurrence in 96.7% of the entire cohort. Cancer-specific survival for 106 patients with sporadic, localized, biopsy proven renal malignancy was 100% at 38.5 months. Biopsies were obtained in 43 patients for a median of 21 months after RFA. Among 38 patients who had biopsy for non-involuting, non-enhancing zones of ablation, three (7.9%) were positive. Investigators concluded short-term cancerspecific survival after RFA remains excellent and most cases are successful based on a combination of imaging and post-ablation biopsies performed almost 2 years after treatment. There were four out of 150 (2.7%) patients who had recurrences with tissue confirmation; one of these patients was detected on imaging and three (2%) were radiologically occult. The absence of enhancement in the setting of noninvoluting lesions is not always a guarantee of a successful ablation. Atwell et al (2013) compared the efficacy and complication rates of percutaneous RFA and cryoablation in the treatment of renal masses measuring 3.0 cm and smaller. A retrospective review was performed of 385 patients with 445 tumors measuring 3.0 cm or smaller treated with thermal ablation from 2000 through 2010. Two hundred fifty-six tumors in 222 patients were treated with RFA (mean [± SD] tumor size, 1.9 ± 0.5 cm), and 189 tumors in 163 patients were treated with cryoablation (mean tumor size, 2.3 ± 0.5 cm). Major complications and efficacy as measured by technical success and local tumor recurrence rates were recorded. There were five (1.1%) technical failures, including one (0.4%) among tumors treated with RFA and four (2.1%) among tumors treated with cryoablation (p = 0.17). Of the 218 tumors treated with RFA and with follow-up beyond 3 months, seven (3.2%) developed local tumor recurrence, at a mean of 2.8 years after treatment (range, 1.2-4.1 years). Of the 145 tumors treated with cryoablation and with follow-up beyond 3 months, four (2.8%) developed local tumor recurrence at a mean of 0.9 years after treatment (range, 0.3-1.6 years). For biopsy-proven renal cell carcinoma, 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). Major complications Radiofrequency Ablation for Renal Cell Cancer Aug 15 6

occurred after 4.3% (10/232) of RFAs and 4.5% (8/176) of cryoablation procedures (p = 0.91). Investigators concluded RFA and cryoablation are both effective in the treatment of renal masses measuring 3 cm or smaller. Major complications with either procedure are infrequent. Psutka et al (2013) assessed the oncologic effectiveness of RFA for the treatment of biopsy-proven RCC. Exclusion criteria included prior RCC or metastatic RCC, familial syndromes, or T2 RCC. Investigators retrospectively reviewed long-term oncologic outcomes for 185 patients with sporadic T1 RCC. Median follow-up was 6.43 yr (interquartile range [IQR]: 5.3-7.7). The chi-square test and Wilcoxon rank-sum tests were used to compare proportions and medians, respectively. Disease-specific survival and overall survival (OS) were calculated using Kaplan-Meier analysis, then stratified by tumor stage, and comparisons were made using log-rank analysis. The 5-yr disease-free survival (DFS) and OS rates are reported. A p value <0.05 was considered statistically significant. Median tumor size was 3 cm (IQR: 2.1-3.9 cm). Tumor stage was T1a: 143 (77.3%) or T1b: 42 (22.7%). Twenty-four patients (13%) were retreated for residual disease. There were 12 local recurrences (6.5%), 6 recurrences in T1a disease (4.2%) and 6 in T1b disease (14.3%) (p=0.0196). Median time to recurrence was 2.5 yr. Local salvage RFA was performed in six patients, of whom five remain disease free at 3.8-yr median follow-up. Tumor stage was the only significant predictor of DFS on multivariate analysis. At last follow-up, 164 patients (88.6%) were disease free (T1a: n=132 [92.3%]; T1b: n=32 [76.2%]; p=0.0038). OS was similar regardless of stage (p=0.06). Five patients developed metachronous renal tumors (2.7%). Four patients developed extrarenal metastases (2.2%), three of whom died of metastatic RCC (1.6%). Investigators concluded in poor surgical candidates, RFA results in durable local control and low risk of recurrence in T1a RCC. Higher stage correlates with a decreased disease-free survival. Long-term surveillance is necessary following RFA. Patient selection based on tumor characteristics, comorbid disease, and life expectancy is of paramount importance. Scientific Rationale Update August 2012 The 2012 National Comprehensive Care Network (NCCN) guidelines Kidney Cancer states, Active surveillance (with delayed intervention if indicated) or thermal ablation techniques such as cryo- or radiofrequency ablation are alternative strategies for selected patients, particularly the elderly and those with competing health risks. Tan et al (2012) reviewed their 10-year experience with RFA, focusing on the outcomes for the incidental benign renal tumor. All small renal masses (SRMs) treated with temperature-based radiofrequency ablation from 2001 to 2011 were reviewed. Of a total of 280 enhancing SRMs biopsied at radiofrequency ablation, 47 were confirmed as benign tumors. Ablation success was defined as the lack of enhancement on the initial postablation axial imaging. Recurrence was defined as tumor growth and enhancement on follow-up axial imaging. Of the 47 benign tumors, 32 were treated percutaneously and 15 laparoscopically. The histologic biopsy finding was angiomyolipoma in 10 and oncocytoma in 37. The median tumor size was 2 cm (range 1-3.6), and the mean follow-up was 45 months. No recurrences developed, and all lesions required only 1 treatment session. The median pre and postoperative glomerular filtration rate was 77 ml/min/1.73 m(2) (range 39-137) and 68 ml/min/1.73 m(2) (range 36-137). The present study was limited by its retrospective nature and small sample population. Authors concluded radiofrequency ablation of SRMs <3.5 cm found to be benign on concurrent biopsy Radiofrequency Ablation for Renal Cell Cancer Aug 15 7

can be efficaciously treated with a single treatment session. Long-term follow-up imaging might not be required if successful ablation is determined at the initial posttreatment cross-sectional imaging study. Nitta et al (2012) evaluated the clinical usefulness of percutaneous RFA. 24 renal tumors in 22 patients who had been diagnosed with T1 stage renal cell carcinoma (RCC) were treated by percutaneous RFA. A LeVeen Needle (Radiotherapeutics) was used with an RF3000 generator. The overlapping ablation method was applied to these tumors, which were larger than 3 cm or located close to the renal hilus. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging was routinely carried out to evaluate the post-treatment state. Maximum tumor diameters ranged from 1.0 to 4.5 cm (mean=2.4 cm). The follow-up period was 1-61 months (mean=18 months) after RFA treatment. Contrast enhancement completely disappeared immediately after this procedure in 23 tumors, the one exception being a 4.5-cm tumor. The tumor recurrence-free and overall survival rates were 85% and 79%, respectively, at two years after RFA. Investigators concluded percutaneous RFA is a feasible option for the treatment of RCCs, particularly for those less than 3 cm in diameter. Zhang et al (2012) reported experience of RFA on 12 patients with synchronous bilateral RCC. From March 2006 to September 2010, 12 patients with bilateral synchronous sporadic renal cell carcinoma (29 lesions overall) were identified from their kidney database. The mean age was 62.3 years (range 35-81). The mean tumor diameter was 4.5 cm (range 0.9-9.0). Three patients received unilateral RFA and contralateral radical nephrectomy, whereas nine patients received bilateral RFA. The oncological and functional outcomes were analyzed. Contrast-enhanced computed tomography examinations were carried out at day 7, and at 3 and 6 months after the procedure, and every 6 months thereafter. The mean follow-up period was 33 months (range 10-64). The local tumor control rate was 93.1% (27/29). Cancer-specific survival and the overall survival rates were 100%. No death or renal failure after the procedure was found. In patients who underwent bilateral RFA, the latest mean glomerular filtration rate had not significantly declined compared with preoperative levels (93.7 ± 13.0 ml/min/1.73 m(2) vs 96.9 ± 13.3 ml/min/1.73 m(2), respectively; P > 0.05). Investigators concluded RFA shows encouraging outcomes in the treatment of bilateral renal cell carcinoma. It can provide adequate local tumor control and cancer-specific survival compared with nephron-sparing surgery while not affecting the renal function. Joniau et al (2011) reviewed the complication rates and local ablative success and long-term oncologic outcomes of recent, larger RFA series. Twelve RFA studies including a minimum of 35 treated tumors, and representing 717 patients were identified and analyzed for local ablative success rates and complications. Reported complications were classified according to Dindo-Clavien. Another five studies representing 172 patients were identified to assess long-term oncologic outcomes. Final pathology revealed 82.3% biopsy-proven RCCs in 8 of the 12 evaluable RFA studies. Local ablative success rates after a first RFA session ranged from 67% to 100%. However, accepting a 8.8% repeat ablation rate, final success rates were 89.7-100%, with 7 of 12 studies showing final ablative success in >95%. These results demonstrate RFA to achieve adequate local tumor control regardless of histology. Risk of complications was 13.2%. Of complications, 10% were minor (grade I or II), while only 3.2% were major complications (grade III). Five papers were identified describing oncological outcome at a minimum follow-up of 53 months (range 53-61.2). Progression-free survival, cancer-specific survival and overall Radiofrequency Ablation for Renal Cell Cancer Aug 15 8

survival ranged from 79.9 to 93.8%, 98 to 100% and 58.3 to 85%, respectively. The reviewers stated this literature review confirms that RFA can deliver durable local tumor control and excellent long-term oncological outcomes. They noted, however, in order to achieve this, a repeat ablation rate of 8.8% has to be accepted. Complication rates are low, with 10% grade I-II and only 3.2% grade >III. These observations render RFA an attractive alternative to surgery in an elderly or comorbid population. Kim et al (2011) reported their results of nephron-sparing RFA of renal tumors. Since August 2004, 49 patients with renal tumors were treated with either percutaneous or laparoscopic RFA. All patients underwent preoperative imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and were suspected to have renal cell carcinoma. The follow-up for each patient included a physical examination, chest radiography, liver function tests, and a contrast-enhanced CT or MRI. To confirm the pathologic criteria of complete ablation, 30 patients underwent 6-month or 1-year follow-up biopsy. Recurrence was defined as growth of the tumor or any new enhancing portions at 3 months after confirmed nonenhancement of the initial RFA lesion. Technical success was achieved in 46/49 cases (94%). The mean tumor size was 2.4 cm and the mean follow-up period was 31.7 months (range, 6-68 months). Of 49 patients, repeated RFA was necessary in 7 patients (14%). Three patients were found to have recurrence at various follow-up intervals. Twenty-three patients (47%) experienced complications, and all but one necessitated intervention. No distant metastasis was found in any cases, and all patients are alive and are being serially followed up. Investigators concluded percutaneous or laparoscopic RFA is considered to be a useful treatment for selected patients with small renal masses and for nephron-sparing. With a mean follow-up of 31.7 months, our intermediate data suggest excellent therapeutic outcome with RFA with effective local tumor control and preservation of renal function. The ultimate role of this modality will continue to evolve and warrants further studies. Gkialas et al (2011) evaluated the feasibility and safety of the minimally invasive percutaneous technique RFA in patients with small RCCs who were unfit for surgery. From January 2008 to November 2009, 7 patients (5 males and 2 females, median age 78 years) with small RCCs were treated with RFA. The indications for RFA were either inoperability due to high cardiovascular and pulmonary risk or a high probability of complete renal failure after nephrectomy. Exclusion criteria were tumor size larger than 6 cm and the localization of the tumor within the renal pelvis. All RFAs were technically successful in terms of complete tumor ablation and all procedures could be done under conscious sedation. Complications after RFA included transient rise in plasma creatinine in 2 patients and hydrocalyx at 18 months in one. The mean hospital stay was 3.14 days (range 2-5). Investigators concluded RFA has limitations such as an uncertain long-term oncological result and need for strict follow up. Physicians must be aware of these limitations and present them clearly to the patients. It is a safe treatment modality that, with longer followup, could play a more important role in the care of patients with renal masses due to its potential for decreased morbidity, shorter convalescence, and the ability to avert the higher risk of extirpative surgery in an aging patient population. Scientific Rationale Update September 2011 American Urological Association (AUA): This statement updated 12/08; now states (in part) "The AUA's National Carrier Advisory Workgroup believes that a 'noncovered decision' on the part of any carrier is neither reasonable nor clinically justifiable and, therefore, respectfully requests that CPT codes 50250, 50542, 50592, Radiofrequency Ablation for Renal Cell Cancer Aug 15 9

and 0135T (50593 in 2008) be found as 'medically reasonable and necessary' in the management and treatment of renal tumors." Scientific Rational Update November 2010 (2010) Per the Medicare LCD on Ablative Therapy (L30312): Although open partial nephrectomy has been the gold standard for excision of renal tumors, minimally invasive approaches offer excellent results with lower morbidity and sparing renal function. The ablative techniques, cryoablation and radiofrequency ablation, have been relatively safe. At present, radiofrequency ablation (RFA) is probably better suited for peripheral, exophytic masses in which higher blood flow and the collecting system are not problems. Indications: 1. Solid renal masses less than or equal to 3 cm. Larger masses would be appropriate in conjunction with vascular or chemical ablation. The larger masses can be devascularized shrinking them to an effective size for treatment. The scanned mass could still be larger than 3cm - (RFA of a renal mass may require multiple cycles of current application with the electrode placed at different sites within the mass. For renal tumors larger than 3 centimeters (cm), re-treatment may be required on a subsequent day with multiple cycles of renal tissue ablation on each day of treatment. In the months following RFA, patients undergo periodic evaluations by CT or magnetic resonance imaging (MRI) to monitor for regrowth of the ablated mass); and; 2. Lesions in solitary kidney or patients with increased surgical risk/renal insufficiency; and 3. A limit of 3 or less lesions; and 4. Biopsy proven or image documentation consistent with renal cell cancer, i.e. characteristics that are suspicious for malignancy. A substantial percentage of patients referred for percutaneous ablation of renal tumors had benign masses. If CT or MRI alone cannot be used to diagnose a benign entity, patients may need to undergo a biopsy before the treatment session. Better techniques for subtyping renal tumors (eg serologic, genetic and/or radiographic) are required to aid in selecting patients who need treatment and determining which of those may be most suitable for ablative therapy. Limitations: 1. Small centrally located lesions or lesions adjacent to the renal hilum should not be considered. 2. Due to risk of tumor spillage from cyst contents with puncture from a cryoprobe, not indicated for primarily cystic lesions. (2010) National Comprehensive Cancer Network (NCCN): Observation or emerging energy ablative techniques (e.g. Cryosurgery or radiofrequency ablation) can be considered for patients who are not surgical candidates. Emerging energy ablative techniques (e.g. Cryosurgery or radiofrequency ablation) are currently considered an option by some experts for selected small tumors. Though a rigorous comparison with surgical resection (i.e. total or partial Radiofrequency Ablation for Renal Cell Cancer Aug 15 10

nephrectomy by open or laparoscopic techniques) has not been done, biopsy of small lesions may be considered to confirm diagnosis of malignancy and guide surveillance strategies. Scientific Rationale Update February 2007 New cases of renal cell carcinoma occur in up to 30,000 people in the United States annually. Renal cancer can occur in one or both of the kidneys. The most common type of renal cancer in adults is renal cell carcinoma (RCC). There are few symptoms in the early stages of renal cancer. The first symptom is often blood in the urine; pain and flank mass are the other classic symptoms. Typically, symptoms develop as the disease progresses, with hematuria, pain, weight loss and a palpable abdominal mass. Some cases are linked to hereditary syndromes. The conventional treatment for renal cell carcinoma has been an open nephrectomy. However, recent advances in surgical techniques have led to the use of partial nephrectomy or laparoscopic nephrectomy in select patients. For some patients, a less invasive treatment would be desirable. For example, given the slow-growing nature of renal cell carcinoma, patients who are poor surgical candidates or have limited life expectancy could benefit from an effective minimally invasive procedure. In addition, a nonsurgical option could also benefit patients with an underlying predisposition to multiple renal cell carcinomas, such as patients with von Hippel- Lindau disease. With advances in computed tomography (CT) and ultrasonography (US) and the increasing use of these modalities, renal cell carcinomas are being detected incidentally at an increasing rate. Moreover, the incidence of renal cell carcinoma may be increasing. Miller et al (2004) Percutaneous radiofrequency ablation (RFA) is a relatively new treatment that is suitable for many patients for whom resection is not possible. The benefits of RFA over resection include reduced treatment related morbidity and mortality, preservation of more functional tissue in the organ, and outpatient treatment. Radiofrequency Ablation (RFA) is supported by the American Urological Association (AUA) as a possible treatment option for renal cancer patients who cannot tolerate a surgical procedure. They state tumor ablation may help to preserve kidney function when multiple tumors are involved. The long-term results are unknown (AUA, 2003). The National Institute for Clinical Excellence (NICE) has published an interventional guidance on RFA for renal cancer (2005). NICE states that RFA may be used in patients unsuitable for surgery who have small renal tumors, or are an anesthetic risk. Cryotherapy may also be a treatment option for patients in whom preservation of renal function is desired in as much as it is possible, for example in patients with a solitary kidney, or with compromised renal function. Even though the evidence is limited, RFA is adequately safe and reduces tumor bulk. NICE also recommends that RFA not be used without arrangements for consent and for audit or research. The Society of Interventional Radiologists (SIR) states RFA may be a treatment option for renal cancer. They state that RFA is especially promising for patients whose cancers cannot be treated surgically. RFA does not rule out other options, and it can be used before or after surgery or radiation therapy, or in addition to systemic treatments (SIR, 2006). Radiofrequency Ablation for Renal Cell Cancer Aug 15 11

Park et al (2006) Studies have been performed at the Department of Urology at the University of Texas on radiofrequency ablation of renal tumors: intermediate-term results. All renal tumors treated using RFA since May 2001 have been recorded in a prospective database. During this time, 94 tumors (mean size 2.4 cm; range 1-4.2 cm) in 78 patients were treated using a temperature-based RFA generator by either a percutaneous (59%) or a laparoscopic approach. The patients followed with imaging at 6 weeks, 3 and 6 months, and every 6 months thereafter. Only patients with at least 12 months of follow-up were eligible for this analysis; the mean followup was 25 months. RESULTS: Of the 89% of masses that were biopsied, 77% were renal-cell carcinomas (RCC), of which 66% were Fuhrman grade 1, 31% were grade 2, and 3% were grade 3. (The Fuhrman system is a four tier nuclear grading scheme for renal cell carcinoma, most frequently used in North America. Grades 1 and 2 are considered low-grade tumors and grades 3 and 4 are regarded as high-grade tumors.) Three recurrences were noted, for an overall recurrence-free rate of 96.8%. In this patient population with numerous comorbid conditions, there were six deaths but only one related to renal cancer, for a cancer-specific survival rate of 98.5% and an overall survival rate of 92.3%. CONCLUSION: In the intermediate term (1-4 years), the oncologic effectiveness of RFA appears comparable to that of traditional treatments offered for small renal masses. Further studies of larger numbers of patients with longer follow-up are needed. Short-term results recorded in evidence-based literature support the use of radiofrequency ablation for the treatment of renal cell carcinoma in patients who are poor surgical candidates. RFA has been shown to be technically feasible and is associated with low morbidity in patients with small, early-stage tumors located primarily at the periphery of the kidney. Continued evaluation is needed to determine long-term outcomes and to compare RFA to partial or total nephrectomy. Although the studies included small sample sizes and short-term follow-ups, most of the literature agreed that RFA is a safe and effective treatment alternative for patients with RCC tumors who are poor surgical candidates. They also agreed that larger studies and randomized control trials are needed to determine the safety and efficacy of RFA compared to surgical intervention and to determine the true longterm oncological effect of RFA. Scientific Rationale - Initial Renal cell carcinoma is the most common form of kidney cancer that occurs among adults. Renal cell carcinomas, which originate within the renal cortex, are responsible for 80 to 85 percent of all primary renal neoplasms. Transitional cell carcinomas of the renal pelvis are the next most common (approximately 8 percent). Other parenchymal epithelial tumors, such as oncocytomas, collecting duct tumors, and renal sarcomas, occur infrequently. Nephroblastoma or Wilms' tumor is common in children (5 to 6 percent of all primary renal tumors), while renal medulla carcinoma appears to be a rare complication of sickle cell disease. Renal cell carcinoma occurs more commonly in men than in women, and as with most forms of cancer, the risk of getting renal cell carcinoma increases with age. Stages of RCC: Stage I: growth or tumor is no larger than 7 centimeters and found in the kidney only Stage II: tumor is larger than 7 centimeters and found in the kidney only Radiofrequency Ablation for Renal Cell Cancer Aug 15 12

Stage III: cancer is found in the kidney and in one nearby lymph node; or in an adrenal gland or in the fatty tissue layer around the kidney, and may be found in one nearby lymph node; or in the main blood vessels of the kidney and may be found in one nearby lymph node Stage IV: cancer has spread beyond the layer of fatty tissue around the kidney and may be found in one nearby lymph node; or to 2 or more nearby lymph nodes; or to other organs, such as the bowel, pancreas, or lungs, and may be found in nearby lymph nodes Radiofrequency ablation (RFA) is a minimally invasive technique that was developed initially to treat inoperable tumors of the liver. It has recently been used instead of partial nephrectomy for the treatment of malignant and benign renal masses. This technique can be performed through a laparoscopic or percutaneous approach and involves the passage of high-frequency electrical currents into the renal mass. Guided by images from intraoperative computed tomography (CT) or ultrasound (US), the surgeon inserts a small electrode into the renal mass. When a highfrequency electrical current is applied, heat generated within the renal mass ablates renal tissue around the electrode. Although heat is generated in the tissue around the electrode rather than in the electrode itself, some RFA systems circulate chilled water or saline through the electrode during thermoablation to minimize charring of renal tissue and to increase the heat-generating capacity of the targeted tissue. According to the American Cancer Society, it is estimated over 35,000 people in 2004 will be diagnosed with renal cell cancer and it will be the cause of death for approximately 12,500. Because the biopsies and imaging that is used to confirm the diagnosis often lead to false-negative or indeterminate results, radical or partial nephrectomy via an open or laparoscopic approach are usually performed. Minimally invasive, nephron-sparing surgical procedures have been developed for patients who are not surgical candidates due to age or comorbid conditions. The literature search identified 10 small studies that met the criteria for detailed review, including 7 prospective, uncontrolled clinical studies; 1 case series; and 2 retrospective studies. These studies evaluated the efficacy and safety of RFA in 8 to 34 patients with solid renal masses less than 3 to 4 cm in diameter. RFA was performed under CT or US guidance. Most patients received conscious sedation, but some patients elected general anesthesia. To assess patient outcomes, all but 1 study involved CT or MRI follow-up examinations at regular intervals after RFA to detect tumor recurrence. Follow-up duration averaged 9 to 17 months for most studies. None of the studies compared RFA with open partial nephrectomy. The use of different types of RFA devices and RFA procedures further complicated comparison of different clinical studies and interpretation of the overall results. In the studies selected for this evaluation, RFA successfully removed renal masses in 93% to 100% of patients. In most cases, a single treatment was sufficient to remove the tumor, but some patients required additional treatments. The results of one small, prospective study suggest that technical success rates may vary with tumor location. In this study, success rates of 100% were achieved for exophytic and parenchymal tumors compared with 25% and 57% for central and mixed tumors, respectively. 7 Treatment success was maintained for at least 12 months in 85% to 96% of patients. RFA was relatively safe and caused mostly mild transient side effects, including postoperative pain and nausea and perirenal hematomas. Some patients experienced more severe complications such as thermal injury to muscles Radiofrequency Ablation for Renal Cell Cancer Aug 15 13

and organs in proximity to the kidney (3.4% to 13%)or hematuria requiring treatment. The largest prospective study (n=34) assessed percutaneous RFA for renal cell carcinoma (RCC) tumors of varying sizes and locations, which were primarily small and exophytic. Based on imaging data from CT and MRI over 13 months of follow-up (range 3 to 43 months), all exophytic and parenchymal tumors were ablated successfully, as were 25% of central tumors and 57% of tumors in mixed locations. Overall, tumor ablation was successful in 82% of the patients. However, as with the other reviewed studies, RFA was evaluated in a small number of patients and there was no direct comparison with traditional surgical techniques. In the next largest prospective trial of RFA (n=29), 94% of lesions required only a single treatment. The remaining lesions were successfully removed during a second procedure. Residual enhancement or recurrence was observed in 2 of 13 lesions for which 12 months follow-up was available. In a retrospective study (n=20), none of the patients experienced tumor recurrence and none of the tumors showed enhancement at a mean follow-up of 9 months (range 1 to 23 months). However, it is not clear for how many patients intermediateto long-term follow-up data were available, and it is possible that most data were derived from short-term follow-up. In the second retrospective study (n=32), a single treatment successfully ablated renal tumors in 26 patients (81%). The remaining 6 patients required a second treatment at an average of 4 months following the first session. The second treatment was successful in 5 of 6 patients. However, the criteria for treatment success were not defined. It is also unclear whether the second treatment was required because of tumor recurrence or tumor regrowth secondary to incomplete ablation. In the 10 studies that met the criteria for detailed review (total patients, n=196), the following complications were reported on a per-patient basis: discomfort during ablation (38%), mild post-treatment discomfort (13%), small infarction in probe path (13%), thermal injury to the ipsilateral psoas and quadratus lumborum muscles (13%), post-treatment increase in serum creatinine (12%), pain during flexion of the hip (10%), ipsilateral numbness (10%), asymptomatic ureteropelvic junction obstruction requiring open surgical repair (6%), transient hypertension (6%), perinephric hematomas (3% to 28%), hematuria (6% to 12%), asymptomatic perirenal fluid collection (5%), proximal urinary stricture requiring nephrostomy (3%), skin metastasis (3%), dilated upper pole calyx (3%), burn injury to liver (3%), and 1 death from pulmonary compromise in a patient with a history of pulmonary compromise who died 3 days following RFA. Review History March 22, 2005 February 2007 November 2010 September 2011 August 2012 August 2013 August 2014 August 2015 Medical Advisory Council Added radiofrequency ablation (RFA) therapy as medically necessary for the treatment of renal masses, up to 4 cm in size, for select patients who meet specific criteria Added Medicare Table with Link to LCD. No revisions. Update. Added Revised Medicare Table with link to LCD. No revisions. Update no revisions Update no revisions. Code updates Update no revisions. Code updates Update no revisions Radiofrequency Ablation for Renal Cell Cancer Aug 15 14

This policy is based on the following evidence-based guideline: 1. National Institute for Clinical Excellence (NICE). Interventional procedures overview of cryotherapy for renal cancers. November 2005. 2. American Urological Association (AUA). Ablation of Renal Masses. Statement by Board of Directors. October 2006. Reaffirmed October 2013. Available at: http://www.auanet.org/about/policy-statements/ablation-of-renal-masses.cfm 3. Hayes. Health Technology Brief. Radiofrequency Ablation for Renal Tumors. January 3, 2009. Updated February 1, 2011. Archived February 3, 2012. 4. National Comprehensive Cancer Network (NCCN). NCCN Practice Guidelines in Oncology. Kidney Cancer. V.2.2010. V.2.2011. Update Version 2.2012. Update Version 1.2013. Version 3.2014. Update version 3.2015 References Update August 2015 1. Allard CB, Coret A, Dason S, et al. Urology. Contrast-Enhanced Ultrasound for Surveillance of Radiofrequency-Ablated Renal Tumors: A Prospective, Radiologist-blinded Pilot Study. Urology 2015 Jun 26. 2. Chang X, Liu T, Zhang F, et al. Radiofrequency ablation versus partial nephrectomy for clinical T1a renal-cell carcinoma: long-term clinical and oncologic outcomes based on a propensity score analysis. J Endourol. 2015 May;29(5):518-25. 3. Cheng X, Gan W, Xu L, et al. Ultrasound-guided percutaneous radiofrequency ablation treatment for renal clear cell carcinoma. Zhonghua Wai Ke Za Zhi. 2014 Nov;52(11):856-60 4. Eisenberg JD, Gervais DA, Singh S, et al. Radiation exposure from CT-guided ablation of renal masses: effects on life expectancy. AJR Am J Roentgenol. 2015 Feb;204(2):335-42. 5. Kim SH, Lee ES, Kim HH, et al. A propensity-matched comparison of perioperative complications and of chronic kidney disease between robotassisted laparoscopic partial nephrectomy and radiofrequency ablative therapy. Asian J Surg. 2015 Jul;38(3):126-33 6. McEachen JC, Leng S, Atwell TD, et al. Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation. Cardiovasc Intervent Radiol. 2015 Jul 10. 7. Miller AJ, Kurup AN, Schmit GD, et al. Percutaneous Clinical T1a Renal Mass Ablation in the Octogenarian and Nonagenarian: Oncologic Outcomes and Morbidity. J Endourol. 2015 Jun;29(6):671-6. 8. Monfardini L, Varano GM, Foà R, et al. Local Recurrence of Renal Cancer After Surgery: Prime Time for Percutaneous Thermal Ablation? Cardiovasc Intervent Radiol. 2015 Apr 23. 9. Pieper CC, Fischer S, Strunk H, et al. Percutaneous CT-Guided Radiofrequency Ablation of Solitary Small Renal Masses: A Single Center Experience. Rofo. 2015 Jul;187(7):577-583. 10. Regier M, Chun F. Thermal Ablation of Renal Tumors: Indications, Techniques and Results. Dtsch Arztebl Int. 2015 Jun 12;112(24):412-8. 11. Sommer CM, Stampfl U, Kauczor HU, Pereira PL. Percutaneous radiofrequency ablation of renal tumors: update 2015. Urologe A. 2015 Feb;54(2):219-30. 12. Tracy CR, Kogan P, Gupta A, et al. Radiation Exposure During Percutaneous Ablation of Small Renal Masses: A Multi-institutional, Multi-modality Analysis. J Endourol. 2015 Jun 23. Radiofrequency Ablation for Renal Cell Cancer Aug 15 15

13. Wagstaff P, Ingels A, Zondervan P, et al. Thermal ablation in renal cell carcinoma management: a comprehensive review. Curr Opin Urol. 2014 Sep;24(5):474-82. References Update August 2014 1. Forauer AR1, Dewey BJ2, Seigne JD3. Cancer-free survival and local tumor control after impendence-based radiofrequency ablation of biopsy-proven renal cell carcinomas with a minimum of 1-year follow-up. Urol Oncol. 2014 Jun 16. pii: S1078-1439(14)00103-3. References Update August 2013 1. 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 Feb;200 (2):461-6. 2. 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 Aug;110(4):510-6 3. Froger L, Neuzillet Y, Lebret T. Indications for ablative treatment in kidney cancer in the elderly. Prog Urol. 2012 Dec;22 (16):1004-9. 4. Karam JA, Ahrar K, Vikram R, et al. Radiofrequency ablation of renal tumours with clinical, radiographical and pathological results. BJU Int. 2013 May;111 (6):997-1005. 5. Psutka SP, Feldman AS, McDougal WS, et al. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol. 2013 Mar;63 (3):486-92. 6. Shah DR, Green S, Elliot A, et al. Current oncologic applications of radiofrequency ablation therapies. World J Gastrointest Oncol. 2013 Apr 15;5(4):71-80. 7. Tsimafeyeu I, Zart JS, Chung B. Cytoreductive radiofrequency ablation in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with sunitinib or interferon-α. BJU Int. 2013 Jul;112(1):32-8. References Update August 2012 1. Gkialas I, Kontraros M, Vassilakis P, et al. Radiofrequency ablation of renal tumors in patients unfit for surgery. Our experience. J BUON. 2011 Apr- Jun;16(2):304-8. 2. Joniau S, Tsivian M, Gontero P. Radiofrequency ablation for the treatment of small renal masses: safety and oncologic efficacy. Minerva Urol Nefrol. 2011 Sep;63(3):227-36. 3. Kim JH, Kim TH, Kim SD, et al. Radiofrequency ablation of renal tumors: our experience. Korean J Urol. 2011 Aug;52(8):531-7. 4. Nakasone Y, Kawanaka K, Ikeda O, et al. Sequential combination treatment (arterial embolization and percutaneous radiofrequency ablation) of inoperable renal cell carcinoma: single-center pilot study. Acta Radiol. 2012 May 1;53(4):410-4. 5. Nitta Y, Tanaka T, Morimoto K,et al. Intermediate oncological outcomes of percutaneous radiofrequency ablation for small renal tumors: initial experience. Anticancer Res. 2012 Feb;32(2):615-8. 6. Tan YK, Best SL, Olweny E, et al. Radiofrequency ablation of incidental benign small renal mass: outcomes and follow-up protocol. Urology. 2012 Apr;79(4):827-30. Epub 2012 Feb 4. Radiofrequency Ablation for Renal Cell Cancer Aug 15 16

7. Zhang S, Zhao X, Ji C, et al. Radiofrequency ablation of synchronous bilateral renal cell carcinoma. Int J Urol. 2012 Mar;19(3):241-7 References Update September 2011 1. Van Poppel H, Becker F, Cadeddu JA, et al. Treatment of Localised Renal Cell Carcinoma. Eur Urol. 2011 Jun 29. [Epub ahead of print] 2. Popovic P, Surlan-Popovic K, Lukic S, et al. Percutaneous imaging-guided radiofrequency ablation of small renal cell carcinoma: techniques and outcomes of 24 treatment sessions in 18 consecutive patients. J BUON. 2011 Jan- Mar;16(1):127-32. 3. Karam JA, Ahrar K, Wood CG, et al. Radio frequency ablation of renal tumors in patients with metastatic renal cell carcinoma. J Urol. 2010 Nov;184(5):1882-7. Epub 2010 Sep 17. 4. Tracy CR, Raman JD, Donnally C, et al. Durable oncologic outcomes after radiofrequency ablation: experience from treating 243 small renal masses over 7.5 years. Cancer. 2010 Jul 1;116(13):3135-42. References Update November 2010 1. Hines-Peralta A, Goldberg SM. Radiofrequency ablation and cryoablation for renal cell carcinoma. UpToDate. April 6, 2009. 2. CMS. Centers for Medicare & Medicaid. LCD for Ablative Therapy (L30312). 10/18/2010. 3. Hui, GC, Tuncali, K, Tatli, S, et al. Comparison of percutaneous and surgical approaches to renal tumor ablation: metaanalysis of effectiveness and complication rates. J Vasc Interv Radiol 2008; 19:1311. 4. Finley, DS, Beck, S, Box, G, et al. Percutaneous and laparoscopic cryoablation of small renal masses. J Urol 2008; 180:492. 5. Liang, P, Wang, Y, Zhang, D, et al. Ultrasound guided percutaneous microwave ablation for small renal cancer: initial experience. J Urol 2008; 180:844. 6. Klingler, HC, Susani, M, Seip, R, et al. A novel approach to energy ablative therapy of small renal tumours: laparoscopic high-intensity focused ultrasound. Eur Urol 2008; 53:810. 7. Beemster, P, Phoa, S, Wijkstra, H, et al. Follow-up of renal masses after cryosurgery using computed tomography; enhancement patterns and cryolesion size. BJU Int 2008; 101:1237. 8. Kunkle, DA, Uzzo, RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer 2008; 113:2671. References Update - February 2007 1. Boss A, Clasen S, Kuczyk M, et al. Image-guided radiofrequency ablation of renal cell carcinoma. Eur Radiol. 2006. 2. Bastide C, Garcia S, Anfossi E, et al. Histologic evaluation of radiofrequency ablation in renal cancer. Eur J Surg Oncol. 2006 Sep 2. 3. Hayes Brief. Radiofrequency ablation for renal tumors. Dec 6, 2005. Lansdale, PA. 4. Ahrar K, Matin S, Wood CG, et al. Percutaneous radiofrequency ablation of renal tumors: technique, complications, and outcomes. J Vasc Interv Radiol 2005;16(5):679-88. 5. Chiou YY, Hwang JI, Chou YH, et al. Percutaneous radiofrequency ablation of renal cell carcinoma. J Chin Med Assoc. 2005;68(5):221-5. 6. Mahnken AH, Rohde D, Brkovic D, et al. Percutaneous radiofrequency ablation of renal cell carcinoma: preliminary results. Acta Radiol. 2005;46(2):208-14. Radiofrequency Ablation for Renal Cell Cancer Aug 15 17

7. Matsumoto ED, Johnson DB, Ogan K, et al. Short-term efficacy of temperaturebased radiofrequency ablation of small renal tumors. Urology 2005. May;65(5):877-81. 8. McDougal WS, Gervais DA, McGovern FJ, et al. Long-term followup of patients with renal cell cardinoma treated with radiofrequency ablation with curative intent. J Urol. 2005;174(1):61-3. 9. Merkle EM, Nour SG, Lewin JS. MR imaging follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: findings in 18 patients during first 6 months. Radiology 2005;235(3):1065-71. 10. Varkarakis IM, Allaf ME, Inagaki T, et al. Percutaneous radiofrequency ablation of renal masses: results at a 2-year mean followup. J Urol. 2005;174(2):456-60. 11. Weizer AZ, Raj GV, O'Connell M, et al. Complications after percutaneous radiofrequency ablation of renal tumors. Urology 2005;66(6):1176-80. 12. Pavlovich CP, Walther MM, Choyke PL, et al. Percutaneous radio frequency ablation of small renal tumours: initial results. J Urol 2002; 167: 10 15. Canadian Cancer Society, et al. Canadian cancer statistics 2005. Toronto: The Society; 2005. 13. Hwang JJ, Walther MM, Pautler SE, et al. Radio frequency ablation of small renal tumors:: intermediate results. J Urol 2004;171(5):1814-8. 14. Lewin JS, Nour SG, Connell CF et al. Phase II clinical trial of interactive MR imaging-guided interstitial radiofrequency thermal ablation of primary kidney tumors: initial experience. Radiology 2004;232(3):835-45. 15. Matsumoto ED, Watumull L, Johnson DB, et al. The radiographic evolution of radio frequency ablated renal tumors. J Uro. 2004;172(1):45-8. 16. Veltri A, De Fazio G, Malfitana V, et al. Percutaneous US-guided RF thermal ablation for malignant renal tumors: preliminary results in 13 patients. Eur Radiol. 2004;14(12):2303-10. 17. Zagoria RJ, Hawkins AD, Clark PE et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR 2004;183(1):201-07. 18. Journal of Vascular and Interventional Radiology 15:97-99 (2004). The Society of Interventional Radiology. Treatment of Renal Cell Carcinoma-associated Dermatomyositis with Renal Arterial Embolization and Percutaneous Radiofrequency Heat Ablation. 19. Gervais, DA, McGovern, FJ, Arellano, RS, et al. (2003) Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiology 226: 417-24. 2004. 20. Mueller PR, Saltalamacchia C, Martino JA, et al. The role of interventional nurses and clinic space in increasing radiofrequency ablation patient volume (liver and kidney) in a busy clinical practice. Radiology 2004; 233(P): 593. 21. Wah TM, Arellano RS, Saltalamacchia C, et al. Image-guided percutaneous radiofrequency ablation and incidence of post-rfa syndrome: A prospective survey. Radiology 2004; 233(P): 655. 22. American Urological Association (AUA). Adult conditions: Kidney cancer. August 2003. 23. Bhayani SB, Clayman RV, Sundaram CP, et al. Surgical treatment of renal neoplasia: evolving toward a laparoscopic standard of care. Urology. 2003;62(5):821-6. 24. Desai MM, Gill IS. Current status of cryoablation and radiofrequency ablation in the management of renal tumors. Curr Opin Urol. 2002;12(5):387-393 25. Linehan WM, Zbar B, Klausner R. Renal Carcinoma. Vogelstein B, Kinzler K, eds. The genetic basis of human cancer. New York: McGraw-Hill, 2002. 26. Kondo K, Yao M, Yoshida M, et al. Comprehensive mutational analysis Radiofrequency Ablation for Renal Cell Cancer Aug 15 18

of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 2002; 34: 58 68. 27. Maranchie JK, Vasselli JR, Riss J, et al. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 2002; 1: 247 55. 28. Linehan WM, Zbar B, Klausner R. Renal carcinoma. The metabolic and molecular basis of inherited disease. 8th edn. New York: McGraw-Hill, 2001:907 References 1. HAYES Technology Assessment Brief Radiofrequency Ablation of Renal Masses Volume VII, Number 7 - July 2004 Accessed: February 22, 2005 2. American Cancer Society (ACS) [Web site]. Estimated New Cancer Cases and Deaths by Sex for All Sites, US, 2004. 2004. Available at: http://www.cancer.org/downloads/med/page4.pdf. Accessed June 21, 2004. 3. National Institute of Clinical Excellence http://www.nice.org.uk/page.aspx?o=73601 Accessed: March 2, 2005 4. Bhayani SB, Clayman RV, Sundaram CP, et al. Surgical treatment of renal neoplasia: evolving toward a laparoscopic standard of care. Urology. 2003;62(5):821-826. 5. Gattinoni L, Alu M, Ferrari L, et al. Renal cancer treatment: a review of the literature. Tumori. 2003;89(5):476-484. 6. National Institutes of Health (NIH). National Cancer Institute (NCI) [Web site]. What You Need to Know About Kidney Cancer. March 30, 2004. Available at: http://www.cancer.gov/cancerinfo/wyntk/kidney. Accessed February 21, 2005. 7. Johnson DB, Cadeddu JA. Radiofrequency ablation of small renal tumors. Expert Rev Anticancer Ther. 2004;4(1):77-83. 8. National Institutes of Health (NIH). National Cancer Institute (NCI) [Web site]. PDQ Cancer Information Summary. National Cancer Institute; Bethesda, MD. Renal Cell Cancer (PDQ?): Treatment?Health Professional. Updated June 6, 2003. Available at: http://www.cancer.gov/cancerinfo/pdq/treatment/renalcell/healthprofessional. Accessed February 21, 2005. 9. Gervais DA, McGovern FJ, Arellano RS, et al. Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiology. 2003;226(2):417-424. 10. Hwang JJ, Walther MM, Pautler SE, et al. Radio frequency ablation of small renal tumors: intermediate results. J Urol. 2004;171(5):1814-1818. 11. Roy-Choudhury SH, Cast JE, Cooksey G, et al. Early experience with percutaneous radiofrequency ablation of small solid renal masses. AJR Am J Roentgenol. 2003;180(4):1055-1061. 12. Ogan K, Jacomides L, Dolmatch BL, et al. Percutaneous radiofrequency ablation of renal tumors: technique, limitations, and morbidity. Urology. 2002;60(6):954-958. 13. Pavlovich CP, Walther MM, Choyke PL, et al. Percutaneous radio frequency ablation of small renal tumors: initial results. J Urol. 2002;167(1):10-15. 14. Rendon RA, Kachura JR, Sweet JM, et al. The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy. J Urol. 2002;167(4):1587-1592. 15. Farrell MA, Charboneau WJ, DiMarco DS, et al. Imaging-guided radiofrequency ablation of solid renal tumors. AJR Am J Roentgenol. 2003;180(6):1509-1513. Radiofrequency Ablation for Renal Cell Cancer Aug 15 19

16. Jacomides L, Ogan K, Watumull L, Cadeddu JA. Laparoscopic application of radio frequency energy enables in situ renal tumor ablation and partial nephrectomy. J Urol. 2003;169(1):49-53. 17. Mayo-Smith WW, Dupuy DE, Parikh PM, et al. Imaging-guided percutaneous radiofrequency ablation of solid renal masses: techniques and outcomes of 38 treatment sessions in 32 consecutive patients. AJR Am J Roentgenol. 2003;180(6):1503-1508. 18. Su LM, Jarrett TW, Chan DY, et al. Percutaneous computed tomographyguided radiofrequency ablation of renal masses in high surgical risk patients: preliminary results. Urology. 2003;61(4 suppl 1):26-33. 19. Friedman, M., et al. Radiofrequency Ablation of Cancer. CardioVasc. and Intervent. Radiol. 2004; 27:427-434 and. Decadt, B. and Siriwardena, A. K. Radiofrequency ablation of liver tumours: systematic review. Lancet Oncol 2004;5: 550-560 20. Livraghi, T., et al. Treatment of Focal Liver Tumors with Percutaneous Radiofrequency Ablation: Complications Encountered in a Multicenter Study. Radiology 2003;226:441-451 21. http://www.cc.nih.gov/drd/rfa/frame-doc.html Accessed: March 1, 2005 Important Notice General Purpose. Health Net's National Medical Policies (the "Policies") are developed to assist Health Net in administering plan benefits and determining whether a particular procedure, drug, service or supply is medically necessary. The Policies are based upon a review of the available clinical information including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the drug or device, evidence-based guidelines of governmental bodies, and evidence-based guidelines and positions of select national health professional organizations. Coverage determinations are made on a case-by-case basis and are subject to all of the terms, conditions, limitations, and exclusions of the member's contract, including medical necessity requirements. Health Net may use the Policies to determine whether under the facts and circumstances of a particular case, the proposed procedure, drug, service or supply is medically necessary. The conclusion that a procedure, drug, service or supply is medically necessary does not constitute coverage. The member's contract defines which procedure, drug, service or supply is covered, excluded, limited, or subject to dollar caps. The policy provides for clearly written, reasonable and current criteria that have been approved by Health Net s National Medical Advisory Council (MAC). The clinical criteria and medical policies provide guidelines for determining the medical necessity criteria for specific procedures, equipment, and services. In order to be eligible, all services must be medically necessary and otherwise defined in the member's benefits contract as described this "Important Notice" disclaimer. In all cases, final benefit determinations are based on the applicable contract language. To the extent there are any conflicts between medical policy guidelines and applicable contract language, the contract language prevails. Medical policy is not intended to override the policy that defines the member s benefits, nor is it intended to dictate to providers how to practice medicine. Policy Effective Date and Defined Terms. The date of posting is not the effective date of the Policy. The Policy is effective as of the date determined by Health Net. All policies are subject to applicable legal and regulatory mandates and requirements for prior notification. If there is a discrepancy between the policy effective date and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. * In some states, prior notice or posting on the website is required before a policy is deemed effective. For information regarding the effective dates of Policies, contact your provider representative. The Policies do not include definitions. All terms are defined by Health Net. For information regarding the definitions of terms used in the Policies, contact your provider representative. Policy Amendment without Notice. Health Net reserves the right to amend the Policies without notice to providers or Members. In some states, prior notice or website posting is required before an amendment is deemed effective. No Medical Advice. The Policies do not constitute medical advice. Health Net does not provide or recommend treatment to members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Radiofrequency Ablation for Renal Cell Cancer Aug 15 20

No Authorization or Guarantee of Coverage. The Policies do not constitute authorization or guarantee of coverage of particular procedure, drug, service or supply. Members and providers should refer to the Member contract to determine if exclusions, limitations, and dollar caps apply to a particular procedure, drug, service or supply. Policy Limitation: Member s Contract Controls Coverage Determinations. Statutory Notice to Members: The materials provided to you are guidelines used by this plan to authorize, modify, or deny care for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract. The determination of coverage for a particular procedure, drug, service or supply is not based upon the Policies, but rather is subject to the facts of the individual clinical case, terms and conditions of the member s contract, and requirements of applicable laws and regulations. The contract language contains specific terms and conditions, including pre-existing conditions, limitations, exclusions, benefit maximums, eligibility, and other relevant terms and conditions of coverage. In the event the Member s contract (also known as the benefit contract, coverage document, or evidence of coverage) conflicts with the Policies, the Member s contract shall govern. The Policies do not replace or amend the Member s contract. Policy Limitation: Legal and Regulatory Mandates and Requirements The determinations of coverage for a particular procedure, drug, service or supply is subject to applicable legal and regulatory mandates and requirements. If there is a discrepancy between the Policies and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. Reconstructive Surgery CA Health and Safety Code 1367.63 requires health care service plans to cover reconstructive surgery. Reconstructive surgery means surgery performed to correct or repair abnormal structures of the body caused by congenital defects, developmental abnormalities, trauma, infection, tumors, or disease to do either of the following: (1) To improve function or (2) To create a normal appearance, to the extent possible. Reconstructive surgery does not mean cosmetic surgery," which is surgery performed to alter or reshape normal structures of the body in order to improve appearance. Requests for reconstructive surgery may be denied, if the proposed procedure offers only a minimal improvement in the appearance of the enrollee, in accordance with the standard of care as practiced by physicians specializing in reconstructive surgery. Reconstructive Surgery after Mastectomy California Health and Safety Code 1367.6 requires treatment for breast cancer to cover prosthetic devices or reconstructive surgery to restore and achieve symmetry for the patient incident to a mastectomy. Coverage for prosthetic devices and reconstructive surgery shall be subject to the co-payment, or deductible and coinsurance conditions, that are applicable to the mastectomy and all other terms and conditions applicable to other benefits. "Mastectomy" means the removal of all or part of the breast for medically necessary reasons, as determined by a licensed physician and surgeon. Policy Limitations: Medicare and Medicaid Policies specifically developed to assist Health Net in administering Medicare or Medicaid plan benefits and determining coverage for a particular procedure, drug, service or supply for Medicare or Medicaid members shall not be construed to apply to any other Health Net plans and members. The Policies shall not be interpreted to limit the benefits afforded Medicare and Medicaid members by law and regulation. Radiofrequency Ablation for Renal Cell Cancer Aug 15 21