Medical Policy

 

Subject: Locally Ablative Techniques for Treating Primary and Metastatic Liver Malignancies
Document #: SURG.00065 Publish Date:    06/28/2017
Status: Revised Last Review Date:    05/04/2017

Description/Scope

This document focuses on surgical excision, cryosurgical ablation, microwave ablation (MWA), radiofrequency ablation (RFA), and percutaneous ethanol injection (PEI) as ablative techniques to treat primary or metastatic cancer of the liver. 

Note: For related topics please see the following:

Position Statement

Medically Necessary:

  1. Surgical Excision*
    1. Surgical excision of primary hepatobiliary carcinoma (including but not limited to hepatocellular carcinoma and cholangiocarcinoma) is considered medically necessary when all of the following criteria are met:
      1. Complete excision of the carcinoma is anticipated; and
      2. Two contiguous hepatic segments are preserved; and
      3. At least 20% of the total estimated liver volume is anticipated to be preserved; and
      4. Extrahepatic disease, if present, has been or will be resected.
    2. Surgical excision of liver metastases from colorectal cancer or functioning neuroendocrine tumors is considered medically necessary when all of the following criteria are met:
      1. Complete excision of the carcinoma is anticipated; and
      2. Two contiguous hepatic segments are preserved; and
      3. At least 20% of the total estimated liver volume is anticipated to be preserved; and
      4. Extrahepatic disease, if present, has been or will be resected; and
      5. If a repeat procedure, at least 6 months have elapsed since the prior surgical resection or ablation.
    3. Surgical excision of liver metastases from other solid tumors is considered medically necessary when all of the following criteria are met:
      1. The presence of 3 lesions or less, as documented by MRI or computerized tomography (CT) scan; and
      2. Each lesion measures no more than 5 centimeters (cm) in diameter; and
      3. Complete excision of the carcinoma is anticipated; and
      4. Two contiguous hepatic segments are preserved; and
      5. At least 20% of the total estimated liver volume is anticipated to be preserved; and
      6. Extrahepatic disease, if present, has been or will be resected; and
      7. If a repeat procedure, at least 6 months have elapsed since the prior surgical resection or ablation.
  2. Other Local Ablative Techniques (specifically, percutaneous ethanol injection, radiofrequency, cryosurgical or microwave ablation):
    1. Other local ablative techniques (specifically, percutaneous ethanol injection [PEI], radiofrequency [RFA], cryosurgical, or microwave ablation) are considered medically necessary in individuals with hepatocellular carcinoma or liver metastases from colorectal cancer or functioning neuroendocrine tumors who meet all of the following criteria:
      1. The individual must be a poor candidate for surgical resection or unwilling to undergo surgical resection; and
      2. The presence of 3 lesions or less, as documented by MRI or computerized tomography (CT) scan; and
      3. Each lesion measures no more than 5 cm in diameter; and
      4. No evidence of extra-hepatic disease; and
      5. All foci of disease are amenable to ablative therapy; and
      6. If a repeat procedure, at least 6 months have elapsed since the prior surgical resection or ablation.
        *Note: When surgical excision and local ablative techniques are used together, the criteria for each technique should be considered.
  3. Bridge to Liver Transplantation
    1. PEI, RFA, or microwave ablation is considered medically necessary as a bridge to liver transplantation, when all of the following criteria are met:
      1. Preserved liver function defined as Childs-Turcotte-Pugh Class A or B; and
      2. Three or fewer encapsulated nodules and each nodule is less than or equal to 5 centimeters in diameter; and
      3. No evidence of extra-hepatic metastases; and
      4. No evidence of severe renal function impairment; and
      5. No evidence of portal vein occlusion.

Investigational and Not Medically Necessary:

Surgical Excision

Surgical excision of liver tumors is considered investigational and not medically necessary when the above criteria are not met.

Ablative Therapies

Ablation by radiofrequency ablation, cryosurgical ablation, microwave ablation, or percutaneous ethanol injection of metastatic lesions of the liver from tumor primaries other than colorectal or neuroendocrine cancer is considered investigational and not medically necessary.

Ablation by radiofrequency ablation, cryosurgical ablation, microwave ablation, or percutaneous ethanol injection of hepatocellular carcinoma or metastatic lesions of the liver is considered investigational and not medically necessary when the above criteria are not met.

Rationale

Surgical excision:

Surgical resection of isolated primary and metastatic tumors continues to be the gold standard for curative intent of colorectal, neuroendocrine and hepatocellular carcinoma (Berber, 2005; Bleicher, 2003; Bruix, 2010; Feng, 2013; Fong, 1999; Lermite, 2005; Solmi, 2006). Alternate ablative techniques may be considered when surgical excision is not feasible due to tumor location, size or residual liver function. Among the other treatment options, there is the greatest data regarding RFA and PEI, but cryosurgery and MWA may also be considered.

Feng and colleagues (2015) conducted a meta-analysis to compare percutaneous RFA and surgical resection as treatments of small hepatocellular carcinoma (HCC). A total of 15,482 individuals from three randomized controlled trials (RCTs) and 20 retrospective studies were included in the efficacy and safety analysis. There were 7524 individuals treated with surgical resection of the liver, and 7958 treated with RFA. At 1, 3 and 5 years, surgical resection had higher overall survival (OS) and recurrence-free rates compared to RFA. OS at 1 year was odds ratio (OR) 0.71 (95% confidence interval [CI], 0.52-0.96); at 3 years OR 0.62 (95% CI, 0.49-0.78) and at 5 years OR 0.55 (95% CI, 0.47-0.66). The surgical resection recurrence-free survival rate at 1 year was OR 0.58 (95% CI, 0.45-0.76); 3 years OR 0.52 (95% CI, 0.40-0.68) and 5 years OR 0.50 (95% CI, 0.34-0.76). There was no difference in mortality between the two groups (OR 0.80; 95% CI, 0.30-2.15). The RFA group had a significantly lower morbidity rate compared to the surgical resection group (OR 0.37; 95% CI, 0.24-0.58).

In a consensus statement by the Society of Surgical Oncology, American Hepato-Pancreato-Biliary Association and the Society for Surgery of the Ailmentary Tract on selecting individuals for resection of hepatic colorectal metastases (Charnsangavej, 2006), the authors concluded that individuals with primary colorectal tumors presenting with synchronous resectable liver metastases should be considered for aggressive curative-intent therapy when appropriate. The authors noted a "paradigm shift" in the definition of resectability noting 20% of the total liver volume "appears to be the minimum safe volume that can be left following extended resection in patients with normal underlying liver." The consensus was:

Feasibility of hepatic resection should also be based on three criteria related to the remaining liver following resection: (1) the ability to preserve two contiguous hepatic segments, (2) preservation of adequate vascular inflow and outflow as well as biliary drainage, and (3) the ability to preserve adequate future liver remnant (greater than 20% in a healthy liver).

The authors reported extrahepatic disease is considered a relative contraindication that requires careful selection when considering liver resection.

A systematic review by Lesurtel and associates (2015) reviewed the benefits and risks of hepatic resection in those with potentially resectable neuroendocrine tumors (NET) with liver metastases. A total of 38 retrospective reviews which included 3425 individuals were reviewed. The authors concluded that hepatic resection with or without ablation could be offered to patients with limited liver or NET. The studies upon which these recommendations were based were retrospective studies and case reviews. There were no randomized, controlled studies. While the studies were of lower quality, the systematic review supports earlier studies on the use of hepatic resection.

The American College of Gastroenterology (ACG) 2014 clinical guideline for the diagnosis and management of focal liver lesions notes that for localized HCC, hepatic resection and radiofrequency ablation are considered curative and have a 5-year survival rate of greater than 50%. The American Association for the Study of Liver Diseases (AASLD) (Bruix, 2011) updated practice guideline for management of HCC includes resection of HCC when a single lesion can be completely resected and the individual is non-cirrhotic or has cirrhosis but still has well preserved liver function, normal bilirubin and hepatic vein pressure gradient less than 10 mmHg.

A panel from the American Society of Clinical Oncology (ASCO) was convened to provide a systematic review of the literature and to provide clinical practice guidelines for the radiofrequency treatment of hepatic metastases from colorectal carcinoma (Wong, 2009). The reviewers determined there were no published randomized controlled trials and the data from 46 unique data sets were extracted from single-arm, retrospective and prospective studies. Therefore, the panel was unable to provide specific clinical practice guidelines, but was able to perform a review of the clinical evidence. Wong and colleagues reported there were a large number of studies demonstrating long-term survival with hepatic resection for approximately 40% of individuals with resectable colorectal hepatic metastases (CRHM). In selected studies, median survival after resection is greater than 40 months and the studies with long-term follow-up have 10-year survival rates of 20%. The panel determined the data demonstrated "extrahepatic disease predicts poor [disease-free survival] DFS and OS after hepatic resection."

Adam and colleagues (2006) reported the results of a retrospective study of 1452 individuals with noncolorectal nonendocrine liver metastases (NCNELM), all of whom received hepatic resection. The most frequent primary sources for the liver metastases were 32% breast, 16% gastrointestinal and 14% urologic. The overall 5-year and 10-year survival rates for all individuals were 36% and 23%, respectively. The median overall survival was 35 months. The median recurrence-free survival was 11 months, and 5 and 10 year recurrence-free survival was 14% and 10%, respectively. Major complications occurred at a rate of 21.5% with a 60-day mortality rate of 2.3%. Although the study data appeared to be encouraging, there was no analysis of how many other individuals with such metastases were refused or otherwise did not receive surgery, or the criteria used in making the decision to operate. Thus, while such a descriptive study showed that longer-term survival may be possible in some individuals and the authors assessed multivariate factors affecting survival, there was no comparison of variables between the surgical group and those with similar disease who never received surgery.

Although there are retrospective studies and case series for hepatic resection of liver metastases from primaries other than colorectal and neuroendocrine tumors, the outcome was generally limited to the feasibility of the resection with suggestion of improved progression-free survival. However, because of the limited data and heterogeneous clinical presentations, optimal selection criteria have not been identified and uniformly adopted. Various authors noted prospective trials are needed to confirm the results. Recommendations for routine hepatic metastasectomy are included in the National Comprehensive Cancer Network® (NCCN® ) Clinical Practice Guidelines (2017) for colorectal cancer, neuroendocrine cancers and solitary melanoma metastasis.

The NCCN Kidney Cancer clinical guideline practice (2017) recommends nephrectomy and surgical metastasectomy for surgical candidates with resectable primary renal cell carcinoma (RCC) and a solitary metastatic site (that is, lung, bone or brain). The majority of individuals will experience recurrence after resection of a solitary metastasis although long term progression-free survival has been reported.

Locally ablative techniques for hepatocellular carcinoma, liver metastases from colorectal carcinoma or neuroendocrine tumors:

The updated AASLD practice guideline (Bruix, 2011) for HCC notes the best treatment option for individuals with early stage HCC who are not suitable for resection or liver transplantation includes percutaneous ablation (injection of ethanol). Other modalities to achieve destruction of the malignant cells include RFA, microwave, laser, and cryotherapy. The guideline also notes "alcohol injection and radiofrequency are equally effective for tumors less than 2 cm." Necrosis rates of 90-100% in HCC smaller than 2 cm treated with PEI have been reported, with a reduction of 70% in tumors between 2-3 cm and 50% in HCC tumors between 3-5 cm (Bruix, 2011).

In a position statement for the Society of Interventional Radiology (SIR), Gervais and colleagues (2009) noted "HCCs 5 cm or less in diameter have a higher probability of having complete ablation compared to those greater than 5 cm in diameter." The authors also noted superior results with tumors smaller than 3 cm, acceptable (intermediate) results with tumors 3 to 5 cm, and "fairly dismal results for tumors larger than 5 cm."

Wong and colleagues (2010) noted 5 year survival rates for RFA of colorectal hepatic metastases varied between 14% to 55% and the local tumor recurrence rates varied between 3.6% to 60%. The reviewing ASCO panel (Wong, 2009) concluded:

There are no compelling data to guide use of RFA in patients with viable extrahepatic disease. Extrahepatic disease is a poor prognostic indicator for patients, predicting decreased disease-free survival (DFS) and overall survival (OS) compared with patients without extrahepatic disease.

The ASCO panel noted the use of palliative RFA when curative treatment was not feasible. However, there were no data to determine the effectiveness of this application. Therefore, the panel recommended future randomized controlled trials to study comparative effectiveness, safety and efficacy.

A 2015 Cochrane review (Weis) evaluated PEI and percutaneous acetic acid injection (PAI) as treatments for early HCC. There were a total of 261 eligible participants in three randomized trials eligible for inclusion in the study. The OS and recurrence-free survival between PEI and PAI were not significantly different as treatments for early HCC. However the authors noted the risk of bias was high in all trials as the number of individuals was limited. 

Lencioni and colleagues (2003) published a randomized comparison of RFA and PEI in 102 individuals with hepatocellular cancer. Tumors were fully ablated in 91% of the participants treated with RFA and 85% of the individuals treated with PEI; however, an average of 5.4 sessions were required for PEI versus 1.1 for RFA. Additionally, there was a significant difference in the local recurrence-free survival rate at 1 year of 83% and 62% at 2 years for the PEI group. In comparison, the RFA group had a local recurrence-free survival rate at 1 year of 96% and 95% at 2 years. The overall 2 year survival was similar in both groups. Additional nonrandomized comparative studies reporting survival data also support the equivalency of these two options (Ikeda, 2001; Livraghi, 1999).

In a study of 153 enrolled individuals with newly diagnosed HCC, Morimoto and colleagues (2007) described two cohorts of participants. A total of 110 individuals received RFA ablation while 43 participants received PEI. Of those, 102 participants had single HCC tumors and 51 participants had two or three HCC nodules with a maximum diameter of 5 cm or less. The overall survival at 3 years was 75% and 59% at 5 years. A total of 125 (82%) individuals had no local tumor at 6 months after initial treatment. Twenty-eight (18%) participants had residual tumor and were retreated. There was no significant difference in successful initial treatment outcomes between the treatment modalities; 90 (82%) of the 110 individuals treated with RFA, and 35 (81%) of 43 individuals treated with PEI, had no residual tumor by contrast enhanced computerized tomography (CT) at 6 months. Median follow-up of 34 months revealed 58 (53%) of 110 individuals treated with RFA and 25 (58%) of 43 individuals treated with PEI had tumor recurrence. Twenty-three participants died and 3 participants were lost to follow-up. Tumor size was one of the pre-treatment factors associated with survival. Overall, the significant predictor of survival was the response to initial treatment.

Taniguchi and colleagues (2008) reported long-term study results of 31 individuals with HCC lesions less than or equal to 15 mm treated with PEI. Overall survival rate at 3, 5, 7 and 10 years was 74.1%, 49.9%, 27.2% and 14.5%, respectively. A subset analysis noted a significant correlation between hepatic function and survival. Individuals with Child-Pugh class A had a higher survival rate compared with Child-Pugh class B (p=0.011).

In 1999, Fong and colleagues proposed a clinical risk score (CRS) as a tool to predict recurrence rates after hepatic resection for metastatic colorectal carcinoma. The CRS tool included multiple liver metastases, size of tumor greater than 5 cm, bilobar liver disease and extrahepatic disease as factors that predicted negative outcomes.

Other studies continue to report on the effects of tumor size and quantity and the impact on the results. Results from PEI on necrosis rates in HCC had a correlation to the tumor size. HCC smaller than 2 cm resulted in 90%-100% necrosis rates, while tumors between 2 cm to 3 cm had a 70% necrosis rate and tumors between 3 cm to 5 cm resulted in 50% necrosis (Bruix, 2005). Lermite and colleagues (2006) reported the significant risk factor that resulted in local recurrence was tumor size greater than 3 cm. In a study by Luo (2005), a lower complete necrosis rate of 23% was reported in a group with tumors larger than 3 cm versus 92.2% in a group with tumors ranging from 1-3 cm. Overall survival was also significant between the groups with an advantage in individuals with smaller tumors less than 3 cm with a 5 year survival of 33.3% compared to 0.4% in the group with tumors larger than 3 cm.

In a randomized controlled trial involving 285 individuals with HCC, the use of PEI treatment was compared to RFA. There were no statistically significant differences between the treatment modalities in the 1, 2, 3, 4 and 5 year survival rates of 95%, 83%, 78%, 70% and 68%, respectively in the PEI cohort, and in the RFA group 95%, 90%, 83%, 73% and 70%, respectively (Giorgio, 2011).

Ablation of larger tumors was more technically challenging as overlapping fields were required to ensure adequate ablation. Radiographic studies present challenges when used to accurately determine the defining margins for overlap. This has been postulated to have been an issue when earlier probes were capable of ablating a maximum of 3 cm (Bleicher, 2003; Muilier, 2005). However, newer probes, electrodes and energy generators are being used in clinical practice. Recent smaller, prospective or retrospective studies have shown some promising results in the treatment of larger lesions with locoregional therapies such as MWA or RFA (Abdelaziz , 2015; Dai, 2015; Veltri, 2015). However, long-term results from randomized studies of ablative therapies (that is, RFA, PEI, microwave ablation or cryosurgery) for treating more than 3 liver lesions or tumors larger than 5 cm are needed to determine safety and effectiveness.

The Agency for Healthcare Research and Quality (AHRQ) (Belinson, 2012) issued an evidence report on the comparative effectiveness and harms of the various local hepatic therapies (including RFA, cryoablation, microwave ablation, hepatic arterial infusion, radioembolization, RFA, stereotactic body radiotherapy, and transarterial chemoembolization [TACE]) for metastases to the liver from unresectable colorectal cancer. The report included 30 articles involving liver-directed therapies. The report states the strength of the evidence (all studies were case series) is insufficient to draw conclusions about overall survival, quality of life, or adverse events. Due to the absence of comparative data, the report is limited in drawing conclusions regarding the efficacy and effectiveness of local hepatic therapies, including RFA, cryoablation and microwave therapy, for individuals with unresectable colorectal cancer metastases to the liver who had no or only minimal evidence of extrahepatic disease, and whose disease was refractory to systemic therapy. Published data on clinical outcomes is limited by the "poor characterization of the patient populations (e.g., number and size of metastases, performance status) and variations in the delivery of the interventions." The report concludes that in the absence of comparative data, "conducting RCTs (ideally head-to-head comparisons) to answer many important questions is desirable, but challenging."

Treatment of neuroendocrine cancers is primarily palliative in nature, to reduce levels of functioning hormones, which may result in significant morbidity. One study reported that radiofrequency ablation resulted in successful treatment of 63% of individuals with functioning neuroendocrine tumors (Henn, 2003).

Locally Ablative Techniques For Metastases From Other Solid Tumors:

Bleicher and colleagues (2003) reported on the use of RFA in a variety of metastatic liver tumors from other primaries, including breast cancer. However the number of tumors other than HCC and colorectal cancer was small. There are multiple small case series reporting on resection or ablative therapies for metastatic liver tumors from other primary sites. However, the cohorts are small and lacking long term follow-up. Treatment may be performed with curative or palliative intent.

Retrospective studies and case series using a locally ablative technique to treat liver metastases from primaries other than colorectal and neuroendocrine tumors generally report the feasibility of the procedure and suggest improved progression-free survival. However, because of the limited data and heterogeneous clinical presentations, optimal selection criteria have not been identified and uniformly adopted. Various authors noted prospective trials are needed to confirm the results. Recommendations (category 1 or 2A) for routine local ablation of hepatic metastases are included in the NCCN clinical practice guidelines (2017) for colorectal cancer and neuroendocrine cancers. However, the treatments are not recommended for other metastatic tumors to the liver.

Large, randomized studies with long-term follow-up need to be completed to determine the safety and efficacy of ablative therapies for liver metastases from tumors other than neuroendocrine and colorectal cancer (Fairhurst, 2016; Kümler, 2015; Seidensticker, 2015).

Cryosurgical Ablation:

Neuroendocrine tumors with a high incidence of distant metastases frequently involve the liver (Bacchetti, 2013). While there is considerable literature regarding cryosurgery, the majority of studies include uncontrolled case series or papers describing technical aspects of this technique. A study compared outcomes between cryosurgery and RFA in individuals with either primary hepatocellular cancer or isolated colorectal metastases (Adam, 2002). Survival at 1 year did not differ between the two treatment modalities.

Bacchetti and colleagues (2013) reported results from a meta-analysis of surgical resection of hepatic metastases and other locally ablative therapies used to treat liver metastases from neuroendocrine tumors. The observational studies included had survival data for analysis. There were 374 individuals with neuroendocrine tumors metastatic to the liver who received conservative treatment and 161 individuals who received treatment for the liver metastases. Those treated with surgical hepatic resection had a significant increase in survival with a hazard ratio (HR) 0.45 (95% CI, 0.34-0.60) compared to the conservative treatment group HR 0.34 (95% CI, 0.21-0.55). The authors concluded hepatic resection of metastatic disease from neuroendocrine tumors resulted in improved overall survival for select individuals. Because the data used in the analysis was derived from observational studies, the authors also noted randomized trials are needed to achieve more evidence to support the role of hepatic resection.

The combined application of cryosurgery and hepatic resection was studied in 40 consecutive individuals with neuroendocrine tumors. The primary endpoint was progression-free survival (PFS) measured from the time of the combined procedures and OS. Individuals were evaluated monthly for the first 3 months and then followed every 6 months. Complete resection was achieved in 24/40 (60%) of the participants while the others had residual microscopic disease. The mean number of tumors ablated with cryosurgery was 2 (range 1-10). The largest lesions treated with cryosurgery had a mean size of 2.4 cm (range 0.3-4.5 cm). The median follow-up period was 61 months (range 1-162 months). The median PFS at 1, 3, 5 and 7 years was 68%, 28%, 17% and 14%, respectively, with a median time to progression of 22 months (range 2-101 months). Median OS was 95 months and 1, 3, 5 and 10 year survival of 92%, 73%, 61% and 40%. The authors noted that the presence of extra hepatic disease (EHD) had an impact on OS (27 months) compared to no EHD (98 months; p=0.004). EHD also had an impact on PFS when present compared to no EHD (9 months vs. 23 months; p=0.039). The authors concluded concomitant hepatic resection with cryosurgery is associated with improved survival outcomes in select individuals (Saxena, 2012).

While RFA appears to be the most common modality used in this country, the choice of ablative technique is often based on individual physician and institution experience and preference.

Microwave Ablation:

Zhang and colleagues (2008) reported on a retrospective study of 160 individuals treated with microwave ablation of liver tumors. Specific diagnoses included primary hepatic cancer (i.e., hepatoma/hepatocellular carcinoma [HCC]) in 97 individuals, and metastatic cancer to the liver from other primary sites in 63 individuals. A mean number of 2.2 microwave applications were performed per person. A second microwave treatment for recurrent disease was performed on 8 individuals, and 2 individuals required a third treatment. A total of 86 individuals were followed for more than 1 year and 96% of individuals treated for primary liver cancer were alive after 1 year versus 82.1% of individuals treated for metastases (p=0.022). One-year OS was 91.8%. Alfa-fetoprotein (AFP) levels in 25 individuals with primary liver cancer decreased from 104.2 ± 22.5 ng/ml to 24.6 ± 3.6 ng/ml (p<0.05) after microwave ablation. There were no operative deaths, and complications were medically managed. Fever was noted in 76.3% of individuals, and was managed with indomethacin. Increased transaminases occurred in 80% (128/160) of individuals, and resolved within a day or two without special treatment in individuals without pre-existing ascites. Pleural effusions were noted in 14 individuals with only 1 individual requiring a chest tube for drainage. The authors concluded microwave ablation therapy was safe and effective for liver tumors. In addition, specialty consensus opinion suggests microwave ablation therapy may be used for primary and secondary liver carcinomas.

Bridge to Liver Transplantation:

As the incidence of HCC continues to rise and availability of donor organs remains low, the waiting time for potentially curative therapy with orthotopic liver transplantation (OLT) increases. Heckman (2008) noted the incidence of disease progression while listed for transplant was 10-23%. Various technologies have been explored to maintain transplant eligibility by controlling disease progression, of which transcatheter arterial chemoembolization (TACE) and RFA were the most frequently studied. A "bridge" to liver transplant involves ablative techniques to minimize and control disease progression to allow individuals with limited HCC to remain eligible on the OLT waitlist. The goal of bridging is to prevent drop-off from the waiting list and to improve post-transplant survival (DuBay, 2011).

The current Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) allocation policy (2017) provides incentives to use loco-regional therapies to downsize tumors to T2 status and to prevent progression while on the transplant wait list. In addition, the OPTN/UNOS policy appears to implicitly recognize the role of loco-regional therapy in the pre-transplant setting. These indications are in part related to the current OPTN/UNOS liver allocation scoring system referred to as the Model for End-Stage Liver Disease (MELD), for adults ages 12 and older, and the Pediatric End-stage Liver Disease (PELD) scoring system for candidates younger than 12 years of age. The MELD score is a continuous disease severity scale incorporating serum bilirubin, prothrombin time (i.e., international normalized ratio-INR), and serum creatinine into an equation, producing a number ranging from 6 (less ill) to 40 (gravely ill). The MELD score estimates how urgently the individual needs a liver transplant within the next 3 months. PELD is similar to MELD but uses additional factors to recognize the specific growth and development needs of children. PELD scores may also range higher or lower than the range of MELD scores. The PELD scoring system includes measures of serum bilirubin, INR, albumin, growth failure, and whether the child is less than 1 year old. Candidates that meet the staging and imaging criteria specified in the OPTN/UNOS Allocation of Livers and Liver-Intestines Policy, Candidates with Hepatocellular Carcinoma (HCC) sections 9.3.G.iv-v may receive extra priority on the "Waiting List." A candidate with an HCC tumor that is stage T2 may be registered at a MELD/PELD score equivalent to a 15% risk of candidate death within 3 months if additional criteria are also met. OPTN/UNOS defines Stage T2 lesions as:

The largest dimension of each tumor is used to report the size of HCC lesions. Nodules less than 1 cm are indeterminate and cannot be considered for additional priority. Past loco-regional treatment for HCC (OPTN Class 5 [T2] lesion or biopsy proven prior to ablation) are eligible for automatic priority. 

The NCCN clinical practice guideline in Oncology for hepatocellular carcinoma (2017) states:

Liver transplantation is a curative option for select resectable patients. Bridge therapy can be considered for patients with HCC to decrease tumor progression and the dropout rate from the liver transplantation waiting list.

The AASLD (Gervais, 2011) lists the following recommendations:

Local ablation is safe and effective therapy for patients who cannot undergo resection, or as a bridge to transplantation. Alcohol injection and radiofrequency are equally effective for tumors <2 cm. However, the necrotic effect of radiofrequency ablation is more predictable in all tumor sizes and in addition its efficacy is clearly superior to that of alcohol injection in larger tumors.

The use of locally ablative techniques such as percutaneous ethanol injection, radiofrequency or microwave ablation may be used as a bridge technique to OLT.

Background/Overview

Primary hepatobiliary carcinoma pertains to malignancies arising from the liver, bile ducts and/or gallbladder. Hepatic carcinoma can arise either as primary liver cancer or by metastasis to the liver from other tissue origins. Malignancies of the liver are comprised primarily of adenocarcinomas classified by hepatocellular and cholangiocarcinoma cell types (National Cancer Institute [NCI], 2017). Hepatocellular carcinoma is the most common form of hepatic malignancies. Gallbladder cancer is the most common type of biliary tract malignancies. Cholangiocarcinoma occurs throughout the biliary tree (NCCN, 2017).

Neuroendocrine tumors may also involve the liver, where hormone production can cause systemic symptoms. The most common neuroendocrine tumor is the carcinoid tumor where excessive hormone production is associated with the carcinoid syndrome, characterized by debilitating flushing, wheezing and diarrhea. Pancreatic endocrine tumors that produce gastrin, insulin or other pancreatic hormones are unusual types of neuroendocrine tumors. Pancreatic endocrine (i.e., islet cell) tumors must be distinguished from the more common pancreatic epithelial tumors that arise from the exocrine portion of the pancreas. Surgical resection is typically not possible for neuroendocrine tumors, and treatment may be focused on palliation of specific systemic symptoms.

Metastases develop in approximately 50-60% of those diagnosed with colorectal cancer and 80-90% of those present with unresectable metastatic liver disease. The extent of hepatic disease at presentation is used to predict disease outcomes. Treatment in those with resectable tumors can be curative. For those individuals who present with a solitary liver lesion 5 cm or less or 3 or less tumors which are 3 cm or less and undergo resection, the 5-year overall survival rate is estimated currently as 81%. (NCCN, 2017).

Local ablative therapy for hepatic metastasis is usually indicated when there is no extrahepatic disease, which rarely occurs for individuals with primary cancers other than colorectal carcinoma or certain neuroendocrine malignancies. Currently, surgical resection with adequate margins or liver transplantation is considered the treatments of choice. However, many individuals are not candidates for surgical resection due to the location or number of lesions, inadequate liver reserve or comorbid conditions. A variety of ablative techniques such as cryosurgical, RFA, MWA or PEI, has been investigated as options for these individuals.

Cryosurgery, also called cryotherapy or cryosurgical ablation, is the use of extreme cold produced by liquid nitrogen (or argon gas) to destroy abnormal tissue. Cryosurgical ablation is performed by inserting a hollow instrument called a cryoprobe into the lesion followed by circulation of coolant such as liquid nitrogen or argon gas through the hollow probe. The physician utilizes imaging procedures such as ultrasound or MRI to guide the cryoprobe to the tumor location and monitor the freezing process. The monitoring process is important so freezing of the cells is limited to the tumor and its immediate area, limiting the amount of damage to nearby healthy tissue. During a cryosurgical procedure, a ball of ice crystals forms around the probe, freezing nearby cells and killing them. The dead tissue is then naturally absorbed by the body. Sometimes more than one probe is used to deliver the liquid nitrogen to various parts of the tumor. Cryosurgical ablation is performed primarily as an open surgical technique; laparoscopic and percutaneous cryoablation have been described but are used infrequently. Cryosurgical ablation may also be performed in conjunction with surgical resection of other lesions or hepatic artery infusion. Cryosurgery does have side effects; however, they may be less severe than those associated with conventional surgery or radiation therapy. In rare cases, cryosurgery may interact adversely with certain types of chemotherapy.

RFA involves inserting an electrode into the center of the tumor with the delivery of alternating current with the intent to destroy tumor cells. Protein denaturation and coagulation is the ultimate cause of cell death. The procedure kills cells (cancerous and normal) by applying a heat-generating rapidly alternating current through probes inserted into the tumor. The effective volume of RFA depends on the frequency and duration of applied current, local tissue characteristics, and probe configuration (for example, single versus multiple tips). RFA can be performed as an open surgical procedure, laparoscopically, or percutaneously with ultrasound or computed tomography (CT) guidance.

MWA is a thermal ablative technique. Probes are percutaneously inserted into the tumor delivering microwave energy into the tumor and heating it to high temperatures and killing cancerous cells. One purported advantage of MWA over RFA is the ability to achieve higher temperatures and obtain a larger ablation zone (Abdelaziz, 2015; Veltri, 2015). For this reason, MWA has generated some interest as a potential therapy for larger lesions although the evidence does not currently support that use.

Percutaneous ethanol injection uses the injection of ethanol directly into tumor tissue, where it destroys the tumor tissue due to its dehydrative and protein degenerative effects. The relative hypervascularity of HCC ensures good penetration of the tumor with minimal spillover of ethanol into normal liver tissue. This treatment has been used more extensively in Italy and Japan where cirrhosis and hepatocellular cancer are endemic. In these countries, screening techniques, such as ultrasound and measurement of alpha-feto protein levels are able to detect small asymptomatic hepatocellular cancers arising in the cirrhotic livers.

Common complications of ablative therapies include abscess formation, infection, hemorrhage and injury to adjacent anatomical organs. There have also been reports of mortalities associated with the ablative procedures.

Definitions

Ablation: The destruction of a body part or tissue or its function, which may be achieved by surgery, hormones, drugs, radiofrequency, heat, or other methods.

Cholangiocarcinoma: A type of cancer developing in cells that line the bile ducts in the liver.

Extra-hepatic disease: Cancer that is located outside of the liver.

Hepatic metastases: Cancer that has spread from its original location to the liver.

Metastasis: The spread of cancer from one part of the body (the origin of the cancer) to another part of the body. A metastatic tumor contains cells that are like those in the original (primary) tumor and have spread.

Neuroendocrine tumor: Tumors arising from cells that produce hormones that can cause systemic symptoms such as flushing or wheezing. Examples of neuroendocrine tumors include, but are not limited to carcinoid tumors, islet cell tumors, medullary thyroid carcinoma, and pheochromocytoma.

Primary hepatocellular cancer: A cancer that originates within liver cells.

Unresectable: Refers to a tumor that cannot safely be removed surgically due to size or location.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Surgical Excision
When services may be Medically Necessary when criteria are met:

CPT  
47120 Hepatectomy, resection of liver; partial lobectomy
47122 Hepatectomy, resection of liver; trisegmentectomy
47125 Hepatectomy, resection of liver; total left lobectomy
47130 Hepatectomy, resection of liver; total right lobectomy
   
ICD-10 Procedure  
0FB00ZZ-0FB04ZZ Excision of liver [by approach; includes codes 0FB00ZZ, 0FB03ZZ, 0FB04ZZ]
0FB10ZZ-0FB14ZZ Excision of right lobe liver [by approach; includes codes 0FB10ZZ, 0FB13ZZ, 0FB14ZZ]
0FB20ZZ-0FB24ZZ Excision of left lobe liver [by approach; includes codes 0FB20ZZ, 0FB23ZZ, 0FB24ZZ]
0FT10ZZ-0FT14ZZ Resection of right lobe liver [by approach; includes codes 0FT10ZZ, 0FT14ZZ]
0FT20ZZ-0FT24ZZ Resection of left lobe liver [by approach; includes codes 0FT20ZZ, 0FT24ZZ]
   
ICD-10 Diagnosis  
C00.0-C96.9 Malignant neoplasms
D01.5 Carcinoma in situ of liver, gallbladder and bile ducts
E34.0 Carcinoid syndrome

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Ablative Techniques
When services may be Medically Necessary when criteria are met:

CPT  
47370 Laparoscopy, surgical, ablation of 1 or more liver tumor(s); radiofrequency
47371 Laparoscopy, surgical, ablation of 1 or more liver tumor(s); cryosurgical
47380 Ablation, open, of 1 or more liver tumor(s); radiofrequency
47381 Ablation, open, of 1 or more liver tumor(s); cryosurgical
47382 Ablation, 1 or more liver tumor(s), percutaneous, radiofrequency
47383 Ablation, 1 or more liver tumor(s), percutaneous, cryoablation
47399 Unlisted procedure, liver [when specified as microwave ablation or percutaneous ethanol injection]
   
ICD-10 Procedure  
0F500ZZ-0F504ZZ Destruction of liver [by approach; includes codes 0F500ZZ, 0F503ZZ, 0F504ZZ]
0F510ZZ-0F514ZZ Destruction of right lobe liver [by approach; includes codes 0F510ZZ, 0F513ZZ, 0F514ZZ]
0F520ZZ-0F524ZZ Destruction of left lobe liver [by approach; includes codes 0F520ZZ, 0F523ZZ, 0F524ZZ]
   
ICD-10 Diagnosis  
C18.0-C18.9 Malignant neoplasm of colon
C19 Malignant neoplasm of rectosigmoid junction
C20 Malignant neoplasm of rectum
C21.0-C21.8 Malignant neoplasm of anus and anal canal
C22.0-C22.9 Malignant neoplasm of liver and intrahepatic bile ducts
C25.4 Malignant neoplasm of endocrine pancreas
C73 Malignant neoplasm of thyroid gland
C74.00-C74.92 Malignant neoplasm of adrenal gland
C75.0-C75.9 Malignant neoplasm of other endocrine glands and related structures
C7A.00-C7A.8 Malignant neuroendocrine tumors
C7B.00-C7B.8 Secondary neuroendocrine tumors
C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct
D01.5 Carcinoma in situ of liver, gallbladder and bile ducts
E34.0 Carcinoid syndrome

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Ablative Techniques for Bridge to Liver Transplant
When services may be Medically Necessary when criteria are met: 

CPT  
47370 Laparoscopy, surgical, ablation of 1 or more liver tumor(s); radiofrequency
47380 Ablation, open, of 1 or more liver tumor(s); radiofrequency
47382 Ablation, 1 or more liver tumor(s), percutaneous, radiofrequency
47399 Unlisted procedure, liver [when specified as microwave ablation or percutaneous ethanol injection]
   
ICD-10 Procedure  
  For the following when specified as PEI, RFA or microwave ablation:
0F500ZZ-0F504ZZ Destruction of liver [by approach; includes codes 0F500ZZ, 0F503ZZ, 0F504ZZ]
0F510ZZ-0F514ZZ Destruction of right lobe liver [by approach; includes codes 0F510ZZ, 0F513ZZ, 0F514ZZ]
0F520ZZ-0F524ZZ Destruction of left lobe liver [by approach; includes codes 0F520ZZ, 0F523ZZ, 0F524ZZ]
   
ICD-10 Diagnosis  
C22.0-C22.9 Malignant neoplasm of liver and intrahepatic bile ducts
C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct
D01.5 Carcinoma in situ of liver, gallbladder and bile ducts
Z76.82 Awaiting organ transplant status

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Abdelaziz AO, Nabeel MM, Elbaz TM, et al. Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis. Scand J Gastroenterol. 2015; 50(4):479-484.
  2. Adam R, Chiche L, Aloia T, et al. Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1452 patients and development of a prognostic model. Ann Surg. 2006; 244(4):524-535.
  3. Adam R, Hagopian EJ, Linhares M, et al. A comparison of percutaneous cryosurgery and percutaneous radiofrequency for unresectable hepatic malignancies. Arch Surg. 2002; 137(2):1332-1339.
  4. Bacchetti S, Bertozzi S, Londero AP, et al. Surgical treatment and survival in patients with liver metastases from neuroendocrine tumors: a meta-analysis of observational studies. Int J Hepatol. 2013; 2013:235040.
  5. Berber E, Felsher N, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastasis. World J Surg. 2002; 26(8):985-990.
  6. Berber E, Pelley R, Siperstein AE. Predictors of survival after radiofrequency thermal ablation of colorectal cancer metastases to the liver: a prospective study. J Clin Oncol. 2005; 23(7):1358-1364.
  7. Berber E, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases. Problems in General Surgery. 2003; 20(3):134-142.
  8. Bergenfeldt M, Jensen BV, Skjoldbye B, Nielsen D. Liver resection and local ablation of breast cancer liver metastases – a systematic review. Eur J Surg Oncol. 2011; 37(7):549-557.
  9. Bleicher RF, Allegra DP, Nora DT, et al. Radiofrequency ablation in 447 complex unresectable liver tumors: lessons learned. Ann Surg Oncol. 2003; 10(1):52-58.
  10. Cassera MA, Hammill CW, Ujiki MB, et al. Surgical management of breast cancer liver metastases. HPB (Oxford). 2011; 13(4):272-278.
  11. Charalampoudis P, Mantas D, Sotiropoulos GC, et al. Surgery for liver metastases from breast cancer. Future Oncol. 2015;11(10):1519-1530.
  12. Cho YK, Rhim H, Noh S. Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: a systematic review. J Gastroenterol Hepatol. 2011; 26(9):1354-1360.
  13. Dai WC, Cheung TT, Chok KS, et al. Radiofrequency ablation versus transarterial chemoembolization for unresectable solitary hepatocellular carcinomas sized 5-8 cm. HPB (Oxford). 2015; 17(3):226-231.
  14. Derek E, Matsuoka L, Alexopoulos S, et al. Combined surgical resection and radiofrequency ablation as treatment for metastatic ocular melanoma. Surg Today. 2013; 43(4):367-371.
  15. DuBay D, Sandroussi C, Kachura JR, et al. Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB (Oxford). 2011; 13(1):24-32.
  16. Fairhurst K, Leopardi L, Satyadas T, Maddern G. The safety and effectiveness of liver resection for breast cancer liver metastases: A systematic review. Breast. 2016; 30:175-184.
  17. Fegrachi S, Besselink MG, van Santvoort HC, et al. Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review. HPB (Oxford). 2014; 16(2):119-123.
  18. Feng K, Yan J, Li X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012; 57(4):794-802.
  19. Feng Q, Chi Y, Liu Y, et al. Efficacy and safety of percutaneous radiofrequency ablation versus surgical resection for small hepatocellular carcinoma: a meta-analysis of 23 studies. J Cancer Res Clin Oncol. 2015; 141(1):1-9.
  20. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999; 230(3):309-321.
  21. Giorgio A, Di Sarno A, De Stefano G, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma compared to percutaneous ethanol injection in treatment of cirrhotic patients: an Italian randomized controlled trial. Anticancer Res. 2011; 31(6):2291-2295.
  22. Gomez D, Malik HZ, Al-Mukthar A, et al. Hepatic resection for metastatic gastrointestinal and pancreatic neuroendocrine tumours: outcome and prognostic predictors. HPB (Oxford). 2007; 9(5):345-351.
  23. Heckman J, Devera M, Marsh J, et al. Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol. 2008; 15(11):3169-3177.
  24. Henn AR, Levine EA, McNulty W, Zagoria RJ. Percutaneous radiofrequency ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol. 2003; 181(4):1005-1010.
  25. Kümler I, Parner VK, Tuxen MK, et al. Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer. Radiol Med. 2015; 120(6):536-541.
  26. Ikeda M, Okada S, Ueno H, et al. Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: a comparative study. Jpn J Clin Oncol. 2001; 31(7):322-326.
  27. Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radiofrequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003; 228(1):235-240.
  28. Lermite E, Lebigot J, Oberti F, et al. Radiofrequency thermal ablation of liver carcinoma. Prospective study of 82 lesions. Gastroenterol Clin Biol. 2006; 30(1):130-135.
  29. Lesurtel M, Nagorney DM, Mazzaferro V, et al. When should a liver resection be performed in patients with liver metastases from neuroendocrine tumours? A systematic review with practice recommendations. HPB (Oxford). 2015; 17(1):17-22.
  30. Li L, Zhang J, Liu X, et al. Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2012; 27(1):51-58.
  31. Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000; 214(3):761-768.
  32. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: treatment with radiofrequency ablation versus ethanol injection. Radiology. 1999; 210(3):655-661.
  33. Lu DS, Yu NC, Raman SS, et al. Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver. Radiology. 2005; 234(3):954-960.
  34. Martin RC, Scoggins CR, McMasters KM. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol. 2010; 17(1):171-178.
  35. Mazzaglia PJ, Berber E, Milas M, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery. 2007; 142(1):10-19.
  36. Meloni MF, Andreano A, Laeseke PF, et al. Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation--intermediate and long-term survival rates. Radiology. 2009; 253(3):861-869.
  37. Morimoto M, Numata K, Sugimori K, et al. Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma. World J Gastroenterol. 2007; 13(7):1003-1009.
  38. Mulier S, Ni Y, Jamart J, et al. Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg. 2005; 242(2):158-171.
  39. Pawlik T, Schulick RD, Choti M. Expanding criteria for resectability of colorectal liver metastases. Oncologist. 2008; 13(1):51-64.
  40. Peng ZW, Zhang YJ, Chen MS, et al. Radiofrequency ablation as first-line treatment for small solitary hepatocellular carcinoma: long-term results. Eur J Surg Oncol. 2010; 36(11):1054-1060.
  41. Petrelli F, Coinu A, Cabiddu M, et al. Hepatic resection for gastric cancer liver metastases: a systematic review and meta-analysis. J Surg Oncol. 2015; 111(8):1021-1027.
  42. Pulitanò C, Bodingbauer M, Aldrighetti L, et al. Liver resection for colorectal metastases in presence of extrahepatic disease: results from an international multi-institutional analysis. Ann Surg Oncol. 2011; 18(5):1380-1388.
  43. Sarmiento JM, Heywood G, Rubin J, et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003; 197(1):29-37.
  44. Saxena A, Chua TC, Chu F, et al. Optimizing the surgical effort in patients with advanced neuroendocrine neoplasm hepatic metastases: a critical analysis of 40 patients treated by hepatic resection and cryoablation. Am J Clin Oncol. 2012; 35(5):439-445.
  45. Saxena A, Chua TC, Chu RC, et al. Impact of treatment modality and number of lesions on recurrence and survival outcomes after treatment of colorectal cancer liver metastases. J Gastrointest Oncol. 2014; 5(1):46-56.
  46. Seidensticker M, Garlipp B, Scholz S, et al. Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study). BMC Cancer. 2015; 15:517.
  47. Siperstein AE, Berber E. Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg. 2001; 25(6):693-696.
  48. Solmi L, Nigro G, Roda E. Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle elect rode in hepatocellular carcinoma. World J Gastroenterol. 2006; 12(7):1098-1104.
  49. Stippel DL, Brochhagen HG, Arenja M, et al. Variability of size and shape of necrosis induced by radiofrequency ablation in human livers: a volumetric evaluation. Ann Surg Oncol. 2004; 11(4):420-425.
  50. Taniguchi M, Kim SR, Imoto S, et al. Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma. World J Gastroenterol. 2008; 14(13):1997-2002.
  51. Tateishi R, Shiina S, Teratani, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1000 cases. Cancer. 2005; 103(6):1201-1209.
  52. Veltri A, Gazzera C, Calandri M, et al. Percutaneous treatment of hepatocellular carcinoma exceeding 3 cm: combined therapy or microwave ablation? Preliminary results. Radiol Med. 2015; 120(12):1177-1183.
  53. Virani S, Michaelson JS, Hutter MM, et al. Morbidity and mortality after liver resection: results of the patient safety in surgery study. J Am Coll Surg. 2007; 204(6):1284-1292.
  54. Yun BL, Lee JM, Baek JH, et al. Radiofrequency ablation for treating liver metastases from a non-colorectal origin. Korean J Radiol. 2011; 12(5):579-587.
  55. Zhang X, Chen B, Hu S, et al. Microwave ablation with cooled-tip electrode for liver cancer: an analysis of 160 cases. Hepatogastroenterology. 2008; 55(88):2184-2187.
  56. Zhang CS, Zhang JL, Li XH, et al. Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis. J BUON. 2015; 20(1):223-230.
  57. Zhong JH, Rodríguez AC, Ke Y, et al. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore). 2015; 94(3):e396.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Gastroenterology. ACG Clinical Guideline: The Diagnosis and Management of Focal Liver Lesions (2014). Available at: http://gi.org/wp-content/uploads/2014/08/ACG_Guideline_Focal_Liver_Lesions_September_2014.pdf. Accessed on March 20, 2017.
  2. American College of Radiology. ACR Appropriateness Criteria®. Radiologic Management of Hepatic Malignancy. Last review date 2015. Available at: https://acsearch.acr.org/list . Accessed on March 15, 2017.
  3. Bala MM, Riemsma RP, Wolff R, Kleijnen J. Cryotherapy for liver metastases. Cochrane Database Syst Rev. 2013;(6):CD009058.
  4. Bala MM, Riemsma RP, Wolff R, Kleijnen J. Microwave coagulation for liver metastases. Cochrane Database Syst Rev. 2013;(10):CD010163.
  5. Belinson S, Chopra R, Yang Y, et al. Local hepatic therapies for metastases to the liver from unresectable colorectal cancer. Comparative Effectiveness Review No. 93. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center under Contract No. 290-2007-10058-I.) AHRQ Publication No. 13-EHC014-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2012. Archived. Available at: http://effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1355. Accessed on March 14, 2017.
  6. Bruix J, Sherman M. American Association for the Study of Liver Disease (AASLD) Practice Guideline: Management of hepatocellular carcinoma. Hepatology. 2005; 42(5):1208-1235.
  7. Bruix J, Sherman M. American Association for the Study of Liver Disease (AASLD) Practice Guideline: Management of hepatocellular carcinoma: an update. Hepatology. 2011; 53(3):1020-1058.
  8. Charnsangavej C, Clary B, Fong, Y, et al. Selection of patients for resection of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006; 13(10):1261-1268.
  9. Cirocchi R, Trastulli S, Boselli C, et al. Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst Rev. 2012;(6):CD006317.
  10. Fedorowicz Z, Lodge M, Al-Asfoor A, Carter B. Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases. Cochrane Database Syst Rev. 2008;(2):CD006039.
  11. Gervais DA, Goldberg SN, Brown DB, et al. Society of Interventional Radiology position statement on percutaneous radiofrequency ablation for the treatment of liver tumors. J Vasc Interv Radiol. 2009; 20(7 Suppl):S342-S347.
  12. Gurusamy KS, Ramamoorthy R, Sharma D, Davidson BR. Liver resection versus other treatments for neuroendocrine tumours in patients with resectable liver metastases. Cochrane Database Syst Rev. 2009;(2):CD007060.
  13. National Cancer Institute (NCI). Adult Primary Liver Cancer Treatment (PDQ® ). Last modified January 31, 2017. Available at: https://www.cancer.gov/publications/pdq/information-summaries . Accessed on March 21, 2017.
  14. National Comprehensive Cancer Network® (NCCN) Practice Guidelines in Oncology™. © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org. Accessed on March 14, 2017.
    • Cervical Cancer (V.1.2017). Revised October 10, 2016.
    • Colon Cancer (V.2.2017). Revised March 13, 2017.
    • Hepatobiliary Cancer (V.1.2017). Revised March 15, 2017.
    • Neuroendocrine Tumors (V.1.2017). Revised February 21, 2017.
    • Rectal Cancer (V.3.2017). Revised March 13, 2017.
    • Soft Tissue Sarcoma (V.2.2017). Revised February 8, 2017.
  15. Organ Procurement and Transplantation Network. United Network for Organ Sharing (UNOS). Policy: 9 Allocation of Livers and Liver-Intestines. Revised March 1, 2017. Available at: http://optn.transplant.hrsa.gov/governance/policies/. Accessed on March 13, 2017.
  16. Riemsma RP, Bala MM, Wolff R, Kleijnen J. Electro-coagulation for liver metastases. Cochrane Database Syst Rev. 2013;(5):CD009497.
  17. Riemsma RP, Bala MM, Wolff R, Kleijnen J. Percutaneous ethanol injection for liver metastases. Cochrane Database Syst Rev. 2013;(5):CD008717.
  18. Weis S, Franke A, Berg T, et al. Percutaneous ethanol injection or percutaneous acetic acid injection for early hepatocellular carcinoma. Cochrane Database Sys Rev. 2015;(1):CD006745.
  19. Weis S, Franke A, Mössner J, et al. Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma. Cochrane Database Sys Rev. 2013;(12):CD003046.
  20. Wong SL, Mangu PB, Choti MA, et al. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010; 28(3):493-508.
Websites for Additional Information
  1. American Cancer Society. Available at: www.cancer.org. Accessed on March 14, 2017.
  2. National Cancer Institute. Adult Primary Liver Cancer (PDQ® ): Treatment. Last modified January 31, 2017. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/adult-primary-liver/healthprofessional/. Accessed on March 14, 2017.
Index

Cryoablation
Hepatic Tumors
Liver Tumors
Microwave Ablation
Percutaneous Ethanol Injection (PEI)
Radiofrequency Ablation (RFA)
Surgical Ablation

Document History
Status Date Action
Revised 05/04/2017 Medical Policy & Technology Assessment Committee (MPTAC) review.
Revised 05/03/2017 Hematology/Oncology Subcommittee review. Updated Rationale, Background, References and Websites sections. Spelled out centimeters in the position statement. Updated formatting in Position Statement section.
Reviewed 05/05/2016 MPTAC review.
Reviewed 05/04/2016 Hematology/Oncology Subcommittee review. Updated Description, Rationale, Background, References and Websites. Removed ICD-9 codes from Coding section.
Revised 05/07/2015 MPTAC review.
Revised 05/06/2015 Hematology/Oncology Subcommittee review. Clarified bridge to transplant nodule size in medically necessary criteria. Updated Rationale, Coding, References and Websites.
  01/01/2015 Updated Coding section with 01/01/2015 CPT changes.
Revised 05/15/2014 MPTAC review.
Revised 05/14/2014 Hematology/Oncology Subcommittee review. Clarified number and nodule size in medically necessary criteria addressing PEI, RFA or microwave ablation as a bridge to liver transplantation. Updated Rationale, References and Websites.
Revised 11/14/2013 MPTAC review.
Revised 11/13/2013 Hematology/Oncology Subcommittee review. Clarified abbreviation in Position Statement. Added medically necessary indication for bridge to liver transplant when criteria are met. Updated Rationale, Coding, References and Websites.
Reviewed 11/08/2012 MPTAC review.
Reviewed 11/07/2012 Hematology/Oncology Subcommittee review. Updated Rationale, References and Websites.
Reviewed 11/17/2011 MPTAC review.
Reviewed 11/16/2011 Hematology/Oncology Subcommittee review. Updated Rationale, References and Websites.
Revised 11/18/2010 MPTAC review.
Revised 11/17/2010 Hematology/Oncology Subcommittee review. Updated Rationale, References and Websites. Rephrased resection criteria. Deleted from resection statements, the criterion for "adequate biliary drainage, vascular inflow, and vascular outflow will be preserved." Reformatted the investigational and not medically necessary statements. Added "hepatocellular carcinoma" into the last investigational and not medically necessary statement.
Reviewed 05/13/2010 MPTAC review.
Reviewed 05/12/2010 Hematology/Oncology Subcommittee review. Updated Rationale, References and Websites.
  10/01/2009 Updated Coding section with 10/01/2009 ICD-9 changes.
Revised 05/21/2009 MPTAC review.
Revised 05/20/2009 Hematology/Oncology Subcommittee review. Fixed formatting in criteria. Added microwave ablation as an example of locally ablative technique. Removed examples of treatment modalities from the title. Updated rationale, references and coding.
Revised 11/20/2008 MPTAC review.
Revised 11/19/2008 Hematology/Oncology Subcommittee review. Revised surgical excision of primary hepatobiliary carcinoma or liver metastases from colorectal cancer and functioning neuroendocrine tumors. Added medically necessary criteria for surgical excision of liver metastases from other solid tumors. Updated references, rationale and coding section.
  10/01/2008 Updated Coding section with 10/01/2008 ICD-9 changes.
Reviewed 05/15/2008 MPTAC review.
Reviewed 05/14/2008 Hematology/Oncology Subcommittee review.
Revised 11/29/2007 MPTAC review.
Revised 11/28/2007 Hematology/Oncology Subcommittee review. Clarified medical necessity statements to include hepatocellular carcinoma. Added CT scan to radiographic criteria. Added investigational and not medically necessary statements for indications when criteria are not met. The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary."
Reviewed 05/17/2007 MPTAC review.
Reviewed 05/16/2007 Hematology/Oncology Subcommittee review. Reviewed literature on tumor size and number of tumors without change to criteria. Updated references, background and coding.
  01/01/2007 Updated Coding section with 01/01/2007 CPT/HCPCS changes; removed CPT 76362, 76394 deleted 12/31/2006.
Revised 06/08/2006 MPTAC review.  Updated references and coding.
Revised 06/07/2006 Hematology/Oncology Subcommittee review. Updated references and coding.
Revised 07/14/2005 MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.
Pre-Merger Organizations Last Review Date Document Number Title
Anthem, Inc.

04/28/2005

SURG.00025 Cryosurgical Ablation of Solid Tumors
 

07/27/2004

SURG.00050 Radiofrequency Ablation of Solid Tumors
WellPoint Health Networks, Inc.

06/24/2004

3.06.03 Locally Ablative Techniques for Treating Primary and Metastatic Liver (Cryosurgical Ablation, Radiofrequency Ablation or Percutaneous Ethanol Injection)