Clinical UM Guideline

This document addresses locally ablative therapies to treat primary or metastatic liver cancer. Treatment goals can be curative, palliative, as a bridge to liver transplantation or downstaging (become eligible for liver transplantation following initial treatment). Locoregional therapies may include any of the following ablative therapies:

• Cryosurgical ablation, or cryotherapy
• Microwave ablation (MWA)
• Percutaneous ethanol injection (PEI)
• Radiofrequency ablation (RFA)

Note: For criteria related to arterially directed therapy to treat solid tumors in the liver, refer to applicable guidelines used by the plan.

Note: For related topics, please see the following:

• CG-SURG-61 Cryosurgical, Radiofrequency, Microwave or Laser Ablation to Treat Solid Tumors Outside the Liver
• MED.00150 Hepzato Kit^™ (melphalan hepatic delivery system)
• SURG.00126 Irreversible Electroporation
• SURG.00165 Histotripsy
• TRANS.00008 Liver Transplantation

Note: For a high-level overview of this document, please see “Summary for Members and Families” below. 

Medically Necessary:

A. Treatment of Hepatic Tumors (Primary or Metastatic)

Any of the following locally ablative techniques are considered medically necessary for individuals with any of the following conditions when all of the criteria below have been met:

1. Techniques
   1. Cryosurgical ablation; or
   2. Microwave ablation (MWA); or
   3. Percutaneous ethanol injection (PEI); or
   4. Radiofrequency (RFA);
      and
2. Conditions
   1. Hepatocellular carcinoma; or
   2. Liver metastases from colorectal cancer; or
   3. Functioning neuroendocrine tumors;
      ​​​​​​​and
3. Criteria
   1. A poor candidate for surgical resection or unwilling to undergo surgical resection; and
   2. Each lesion measures no more than 5 cm in diameter; and
   3. No or minimal extra-hepatic metastases; and
   4. All foci of disease are amenable to ablative therapy or surgical resection.

B. Bridge to Liver Transplantation

Any of the following locally ablative techniques (MWA, PEI, RFA) 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 portal vein occlusion.

C. Hepatocellular Carcinoma in Individuals Who May Become Eligible for Liver Transplantation (Downstaging)

Any of the following locally ablative techniques (PEI, RFA) is considered medically necessary for the treatment of an individual when both of the following criteria are met:

1. May become eligible for liver transplantation except that the hepatic lesion(s) size is greater than 5 centimeters in maximal diameter; and
2. It can be reasonably expected that treatment will result in tumor size reduction to less than or equal to 5 centimeters in maximal diameter.

Not Medically Necessary:

Locally ablative techniques are considered not medically necessary when the criteria above are not met.

This document describes clinical studies and expert recommendations, and explains when treatments that directly destroy tumors in the liver may be appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Ablative therapy is a way to treat liver cancer or cancer that has spread to the liver. It uses different techniques to destroy tumors without removing them. These methods include cryoablation (freezing the tumor), heat-based methods such as microwave ablation (MWA) or radiofrequency ablation (RFA), and percutaneous ethanol injection (PEI) that kills tumor cells by injecting alcohol into the tumor. These treatments may be used to try to cure the cancer, to relieve symptoms, to prepare someone for a liver transplant, or to shrink tumors so a person can later become eligible for transplant. These options are often used for people who cannot have more invasive types of surgery or choose not to have it. Each method has pros and cons, and none has been proven better than the others. They are usually used for small tumors (5 cm or less). Larger tumors are harder to treat this way. Side effects can include infection, bleeding, or damage to nearby organs. For some people, these treatments may help control the disease and improve survival, but they have not been shown to help in all cases.

What the Studies Show

These types of treatments are most helpful when used for small tumors or in people who cannot have surgery. Studies show that RFA and MWA are safe and effective for liver tumors that are 5 cm or smaller. Both methods work well, and neither has been shown to be better overall. RFA may lead to fewer tumor recurrences than PEI, but the overall survival is similar between these two methods. Studies have not shown that ablation works well for tumors larger than 5 cm. Standard surgical methods remain the best option for people who can tolerate it. For people with colorectal cancer or neuroendocrine tumors that have spread to the liver, ablation can help control the disease when surgery is not possible. There is not enough good evidence to support using ablation for pancreatic cancer. For people waiting for a liver transplant, ablation may help keep the cancer from getting worse so they stay eligible for a transplant. This is called “bridge therapy.” People with liver cancer that is slightly too large for transplant may also get ablation to shrink the tumor enough to qualify for a transplant. This is called “downstaging.” These approaches may lead to better outcomes after transplant. Better studies are needed to know if ablation helps in all of these cases.

When is Ablative Therapy Clinically Appropriate?

Ablative therapy (cryoablation, MWA, PEI, or RFA) may be appropriate in these situations:

• People with hepatocellular carcinoma, colorectal liver metastases, or functioning neuroendocrine tumors; and
• Who cannot or do not want to have surgery; and
• Each tumor is 5 cm or smaller; and
• Disease outside the liver is very limited or not present; and
• All tumors can be fully treated with ablation or surgery

Ablative therapy (MWA, PEI, or RFA) may also be used as a bridge to liver transplant when:

• Liver function is preserved (Child-Turcotte-Pugh class A or B); and
• There are three or fewer liver tumors, each 5 cm or smaller; and
• No cancer has spread outside the liver; and
• No blockage in the portal vein

Ablative therapy (PEI or RFA) may be used for people who may become eligible for liver transplant if:

• The tumor is currently too large (over 5 cm) but could shrink to 5 cm or less with treatment

When is this not Clinically Appropriate?

Ablative therapy is not clinically appropriate when the above conditions are not met. This includes tumors larger than 5 cm that cannot be shrunk, or when the cancer has spread too far outside the liver. Studies show that these treatments are less effective or do not work in those cases. Unnecessary treatments can lead to treatment that does not help and may cause side effects. Ablative therapy is not clinically appropriate in scenarios other than those listed above.

(Return to Description)

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

Cryosurgical ablation
When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for situations designated in the Clinical Indications section as not medically necessary.

Radiofrequency, Microwave, Percutaneous Ethanol Injection ablation
When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met.

Summary

Locally ablative therapies are established liver-directed treatment options for selected individuals with primary or metastatic hepatic malignancies when surgical approaches are not feasible. Techniques such as RFA, MWA, PEI, and cryoablation provide effective local tumor control for small, well-defined lesions, with outcomes strongly influenced by tumor size, location, liver reserve, and completeness of ablation. Evidence consistently demonstrates improved local control and survival for lesions ≤ 3 cm, with reduced effectiveness for tumors larger than 5 cm. Comparative studies do not demonstrate clear superiority of one modality over another, and selection is guided by tumor characteristics and institutional expertise. Clinical practice guidelines from the National Comprehensive Cancer Network (NCCN), American Association for the Study of Liver Diseases (AASLD), and Society of Interventional Radiology (SIR) support the use of ablation as a definitive or organ-sparing option in appropriately selected cases, including liver-limited disease from colorectal and neuroendocrine primaries.

Ablative therapies are also integral to transplant-related liver cancer management strategies. NCCN and AASLD guidelines recognize locoregional ablation as an effective approach to control disease progression, preserve transplant eligibility, and, in select circumstances, reduce tumor burden to within accepted transplant criteria. Studies demonstrate that favorable response to pre-transplant ablation is associated with post-transplant outcomes comparable to those observed in individuals meeting criteria at initial presentation. National transplant policies from the Organ Procurement and Transplantation Network (OPTN) and the United Network for Organ Sharing (UNOS) further acknowledge the role of locoregional therapy within allocation frameworks, reinforcing its incorporation into multidisciplinary liver cancer care.

Discussion

Description and Prevalence

According to the American Cancer Society (ACS), there will be an estimated 42,340 new cases of primary liver cancer and intrahepatic bile duct cancer diagnosed in the United States (U.S.) in 2026 and approximately 30,980 deaths associated with the disease. Since 1980, the incidence of hepatic cancer has more than tripled and the increasing incidence attributed to high rates of hepatitis C (HCV), nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome (Heimbach, 2017). More than 80% of the individuals diagnosed with hepatocellular carcinoma (HCC) are found to have pre-existing cirrhosis (Marrero, 2018). The presence of an underlying liver disease not only increases the chance of liver cancer development, it also complicates treatment.

Primary HCC pertains to malignancies arising from the liver, while hepatobiliary cancers originate from bile ducts and/or gallbladder. These groups of malignancies are collectively known as intrahepatic and extrahepatic cholangiocarcinoma. 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. Hepatocellular carcinoma is the most common form of hepatic malignancies and makes up 90% of the cases. Gallbladder cancer is the most common type of biliary tract malignancies. Cholangiocarcinoma occurs throughout the biliary tree.

Extrahepatic Disease

At initial diagnosis, extrahepatic metastases are detected in 13-36% of HCC cases. At autopsy, approximately 68% of cases are found to have extrahepatic disease, showing that imaging is underestimating the extent of disease or metastases are developing during or following treatment. Post-instrumentation seeding of HCC can occur following biopsies or percutaneous ablation. Also, tumors may rupture or slough off cells during arterially directed therapies, resulting in extrahepatic spread (Arora, 2021). There is no specific definition of oligometastatic disease, but for this guideline it is defined as up to 5 lesions extrahepatic lesions (Lievens, 2020).

Liver metastases can develop from any type of cancer, but metastases from colorectal cancer (CRC) are the most common. Metastases develop in approximately 50-60% of those diagnosed with CRC and 80-90% of those individuals present with unresectable metastatic liver disease. Stewart and associates (2018) analyzed survival times and palliation in those with CRC metastases. The median survival of individuals with unresectable metastases to the liver is 13 months. The median survival of individuals with extrahepatic metastases ranges from a low of 19 months in bone metastases to 36 months in brain metastases. Metastases to the liver largely determine the length of survival in CRC. Over 70% of individuals with unresectable liver metastatic disease will die from liver metastases. The authors note the following for individuals with CRC metastases:

Disease specific survival is also significantly shorter for those who die of liver metastasis, compared to patients who die from other metastatic sites. Thus, addressing liver metastases initially is the most clinically relevant, since this is the most life limiting. Currently, patients who do not undergo surgical treatment of liver metastases typically live less than 18 months, with no 5-year survivors. By comparison, those who are resected but recur have a median survival of 40 months, and have a 17% 5-year survival. As such, liver directed therapies shift the cause of death to other sites at a later time point. For this reason, having metastases at other sites does not change survival for patients with liver metastases, as long as they are candidates for surgery.

The NCCN clinical practice guideline (CPG) for HCC (V2.2025) includes ablation techniques as an option for HCC with minimal or uncertain extrahepatic metastases, if surgery is not an option. While early reports indicated that the use of locoregional techniques in individuals with extrahepatic are associated with poorer prognostic outcomes (Wong, 2009), locoregional techniques appear to provide improved survival times in individuals with extrahepatic metastasis when hepatic lesions are treated.

Ablative Techniques (Cryoablation, RFA, MWA or PEI)

Local ablative therapy for hepatic metastases is generally indicated when there is no extrahepatic disease or when all disease sites can be treated, most commonly in individuals with colorectal cancer or select neuroendocrine tumors. Surgical resection with adequate margins or liver transplantation remain the preferred and potentially curative treatments; however, ablative therapy may be considered curative for small lesions or for individuals who are not surgical candidates due to tumor location or burden, limited hepatic reserve, or comorbid conditions (NCCN, V2.2025). Complications of ablative therapies include abscess formation, infection, hemorrhage, injury to adjacent organs, and rare treatment-related death.

Ablative modalities include cryoablation, radiofrequency ablation (RFA), microwave ablation (MWA), and percutaneous ethanol injection. Cryoablation destroys tissue using extreme cold delivered via cryoprobes, with necrotic tissue subsequently absorbed by the body and typically fewer side effects than surgery or radiation. RFA uses heat generated by alternating electrical current to induce coagulative necrosis and may be performed surgically or percutaneously under imaging guidance. MWA is another heat-based technique capable of achieving higher temperatures and larger ablation zones than RFA (Abdelaziz, 2015; Veltri, 2015). Percutaneous ethanol injection (PEI) induces tumor necrosis through dehydration and protein denaturation.

Overall, studies do not show that any of these specific ablative techniques are superior to the others. 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. Locally ablative techniques are frequently used with resective surgery.

Primary Liver Disease

NCCN guidelines for HCC (V2.2025) note RFA as a potential curative option for select early-stage individuals who are not surgical candidates. The NCCN CPG for HCC (V2.2025) states the following with Category 2A recommendations in the Principles of Locoregional Therapy-Ablation section:

• Locoregional therapy should be considered in patients who are not candidates for surgical curative treatments, or as a part of a strategy to bridge patients for other curative therapies.
• All tumors should be amenable to ablation such that the tumor and, in the case of thermal ablation, a margin of normal tissue is treated. A margin is not expected following percutaneous ethanol injection.
• Tumors should be in a location accessible for percutaneous/laparoscopic/open approaches for ablation.
• Caution should be exercised when ablating lesions near major vessels, major bile ducts, diaphragm and other intra-abdominal organs.
• Ablation alone may be curative in treating tumors less than or equal to 3 cm. In well-selected patients with small properly located tumors, ablation should be considered as definitive treatment in the context of a multidisciplinary review. Lesions 3 to 5 cm may be treated to prolong survival using arterially directed therapies, or with combination of an arterially directed therapy and ablation as long as tumor location is accessible for ablation.
• Unresectable/inoperable lesions greater than 5 cm should be considered for treatment using arterially directed therapy, systemic therapy, or EBRT.

The NCCN CPG for biliary tract cancers (V2.2025) recommend that individuals be evaluated for potentially curative therapies. For individuals who are not surgical candidates, locoregional therapies, including ablation, are an option when the tumor is amenable to complete ablation.

The 2023 recommendations by the AASLD (Singal, 2023) addressing treatment of HCC with ablative therapies include the following recommendations:

• Patients with solitary tumors ≤5 cm should be treated with curative intent using local ablative therapies if they are ineligible for or decline surgical therapy (Level 1, Strong Recommendation).
• Thermal ablation (radiofrequency or microwave ablation) should be considered the treatment of choice for patients with early stage HCC ≤3 cm who are ineligible for or decline surgery (Level 1, Strong Recommendation).
  a. AASLD does not advise one thermal ablative modality over another.

In a position statement for the Society of Interventional Radiology (SIR) regarding percutaneous RFA in treating liver tumors, Gervais (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.”

Feng (2015) conducted a meta-analysis to compare percutaneous RFA and surgical resection as treatments of small HCC. A total of 15,482 individuals from 3 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 OS and recurrence-free rates compared to RFA. There was no difference in mortality between the two groups, but the RFA group had a significantly lower morbidity rate compared to the surgical resection group.

Chong and associates (2020) compared the safety and efficacy outcomes of RFA and MWA in individuals with unresectable HCC (n=93) in a prospective randomized study. Participation was limited to those with lesions 3 cm or less, a maximum tumor diameter of 5 cm or less and an absence of extrahepatic metastasis. Participants were randomized to receive either RFA (n=46) or MWA (n=47). The MWA compared to RFA 1-year, 3-year, 5-year OS rates were 97.9%, 67.1%, 42.8% and 93.5%, 72.7% and 56.7% respectively (p=0.899). There were no cases of treatment- related mortality at 30 days. The authors concluded that both procedures were equally safe and effective in treating small HCC. MWA did show shorter ablation times and no risk of burn injury. Other studies support the finding that MWA and RFA therapy produce similar clinical outcomes in a comparable population (Kamal, 2019; Vietti Violi, 2018; Yu, 2017; Zhang, 2008)

In a systematic review, Shen and associates (2013) assessed clinical outcomes of each therapy, including survival, recurrence and major complications in individuals with HCC lesions less than 3 cm. While RFA was shown to have a higher 3-year OS rate and a lower rate of local recurrence, there was no difference between the therapies in terms of distant intrahepatic recurrence. RFA was associated with a higher rate of complications. RFA and PEI appear to have similar outcomes in individuals with early HCC (three or less lesions which are 5 cm or smaller) (Ikeda, 2001; Giorgio, 2011; Lencioni, 2003; Livraghi, 1999). Response to the initial treatment appears to be a significant predictor in survival rather than the type of ablation therapy (RFA vs. PEI) used (Morimoto, 2007). Other studies evaluating PEI therapy have shown that hepatic function, Child-Pugh classification, and tumor size affect survival rates and individuals with tumors 3 cm or less with improved survival rates compared to larger tumors (Bruix, 2005; Lermite, 2006; Luo, 2005; Taniguchi, 2008).

Lencioni (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 compared to 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 (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 tumor and 51 participants had two or three HCC nodules with a maximum diameter of 5 cm or less. The overall survival (OS) at 3 years was 75% and 59% at 5 years. No local tumor growth at 6 months following initial treatment was reported in 125 (82%) individuals. 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.

The current RFA devices are capable of producing a lesion of 5 cm or more in one session. This is sufficient to allow for the full ablation of a 3 cm tumor with adequate margins (Peng, 2013; Tovoli, 2016). 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. There have been several 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, at this time, the use of ablative therapies have not been shown in studies to be clinically appropriate in the treatment tumors larger than 5 cm.

Metastatic liver lesions

Liver metastases are common because the liver filters a large volume of blood (including venous drainage from much of the gastrointestinal tract). Primary cancers frequently associated with liver metastases include colorectal, breast, pancreatic and neuroendocrine tumors (NETs). Prognosis and treatment depend heavily on the primary tumor biology and whether the liver disease is limited and potentially controllable with local therapy.

Colorectal liver metastases

The safety and efficacy of thermal tumor ablation for colorectal liver metastases have been well-established (Chlorogiannis, 2023; Meijerink, 2018; Ruers, 2017; Shady, 2018). These studies demonstrate that, in appropriately selected individuals with limited liver disease, thermal ablation achieves high rates of complete tumor eradication and durable local control with low procedure-related morbidity and mortality. Outcomes are particularly favorable for small lesions treated with adequate ablative margins. Randomized prospective data show improved survival when ablation is incorporated into multidisciplinary management compared with systemic therapy alone. Collectively, this evidence supports thermal ablation as an effective, organ-sparing alternative or adjunct to surgical resection for colorectal liver metastases.

The NCCN CPGs for Colon Cancer (V5.2025) and Rectal Cancer (V4.2025) consider ablative techniques to be appropriate treatments for colorectal cancer liver metastases. Surgical resection is preferred when feasible; however, ablation may be used alone or in combination with resection for individuals with liver-limited or oligometastatic disease, particularly when lesions are small (3 cm or less) and can be completely treated with adequate margins. The guidelines explicitly state that, for small liver metastases, thermal ablation is considered equivalent to resection, supporting its use when surgery is not possible due to anatomic constraints, comorbidities, limited hepatic reserve, or individual preference. Ablation is also endorsed for recurrent disease after prior hepatectomy or ablation, provided all visible disease is amenable to complete treatment, and as part of conversion strategies following systemic therapy for initially unresectable disease.

Neuroendocrine liver metastases

Neuroendocrine tumors may also involve the liver, where hormone production can cause systemic symptoms. The most common neuroendocrine tumor is the carcinoid tumor. These tumors are associated with excessive hormone production leading to carcinoid syndrome. Carcinoid syndrome is characterized by debilitating flushing, wheezing, and diarrhea as well as other less frequently occurring symptoms. Pancreatic endocrine tumors that produce gastrin, insulin or other pancreatic hormones are unusual types of neuroendocrine tumors. Pancreatic endocrine (islet cell) tumors differ 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 tends to focus on palliation of specific systemic symptoms.

Neuroendocrine tumors with a high incidence of distant metastases frequently involve the liver (Bacchetti, 2013). Treatment of neuroendocrine cancers is primarily palliative in nature with a goal to reduce levels of functioning hormones. Considerable literature regarding the use of ablative techniques shows an increase in survival times when compared to conservative treatment in select individuals or to reduce levels of functioning hormones (Adam, 2002; Bacchetti, 2013; Henn, 2003; Saxena, 2012).

The NCCN CPGs for Neuroendocrine Tumors (V3.2025) recommend image-guided thermal ablation (radiofrequency or microwave) as a liver-directed treatment option for individuals with neuroendocrine tumor liver metastases, particularly in the setting of liver-dominant disease. Thermal ablation may be used alone or in combination with surgical resection to achieve cytoreduction, control tumor burden, and alleviate hormone-related symptoms when complete resection is not feasible. A 2025 American Society of Clinical Oncology (ASCO) guideline on symptom management in well-differentiated neuroendocrine tumors (Perez, 2025) contains the following thermal ablation recommendation regarding functioning pancreatic NET:

Thermal ablation may be offered to patients with unresectable GEP-NET (gastroenteropancreatic neuroendocrine tumors) hepatic metastases, alone or in combination with surgery, when lesions are limited in size and number, and single lesions are rapidly growing. (Evidence quality: Low; Strength of recommendation: Conditional)
Qualifying statement for Recommendation 5.5: Ablation is associated with more favorable outcomes when tumors are ≤3 cm.

Pancreatic liver metastases

Liver metastases occur in up to 80-90% of metastatic pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer. Current standards of care recommend systemic therapy (eg, FOLFIRINOX or gemcitabine-based regimens), which remains the only treatment shown to improve survival in stage IV disease. The limited published evidence on liver-directed ablation for PDAC consists only of small, retrospective RFA series performed in highly selected individuals with liver-only, low-burden disease after prior pancreatectomy, and no robust randomized data exist (Wang, 2023; Wang, 2024). The NCCN Guideline on pancreatic adenocarcinoma (V2.2025) recommends that individuals with metastatic disease be managed with systemic therapy because the disease is fundamentally systemic in behavior. The NCCN does not recommend the use of any locoregional ablative techniques to treat pancreatic adenocarcinoma.

Liver metastases from sarcomas

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal malignancies that account for approximately 1% of adult cancers. Although gastrointestinal stromal tumors (GIST) are classified within STS group, their distinctive biologic behavior and clinical course warrant consideration as a separate disease entity with unique standards of care. Up to 50% of affected individuals develop metastatic disease, most commonly to the lungs, followed by the liver. The liver is the most dominant metastatic site in GIST. Despite treatment, the prognosis for metastatic soft tissue sarcomas remains poor, reflecting advanced-stage disease (Burkhard-Meier, 2024).

There is little evidence to support the use of ablative therapies in treating liver metastasis from STS. Arterially directed or systemic therapies are frequently utilized, particularly in those with multiple unresectable liver lesions (Gronchi, 2016). While the NCCN CPG on STS (V1.2025) does include local ablation treatment as an option associated with improved overall survival in individuals with oligometastatic disease, no supportive studies were cited. The NCCN CPG for GIST (V1.2026) notes that ablation may be considered as a liver-directed treatment option in select cases of hepatic metastatic disease, particularly in the setting of limited disease burden or when surgical resection is not feasible. However, the supporting evidence remains limited and is derived primarily from small retrospective series and highly selected populations. The role of thermal ablation is not well defined and there is a paucity of high-level data informing outcomes.

Breast cancer liver metastases (BCLM)

Approximately 15% of individuals with breast cancer develop liver metastases. The current standard of care for BCLM is systemic chemotherapy with or without hormonal therapy, based on tumor receptor status (Rangarajan, 2023). Prognosis remains poor, with median survival reported at approximately 19-26 months with systemic therapy alone. The NCCN CPGs for Breast Cancer (V1.2026) do not address or recommend thermal ablation techniques for the treatment of BCLM. Evidence evaluating liver-directed ablative therapies is limited to retrospective, single-center studies with methodological limitations and significant selection bias. While some studies suggest improved survival in highly selected individuals with liver-confined oligometastatic disease, the absence of randomized controlled trials and standardized selection criteria limits the quality of evidence supporting thermal ablation in this population (Bai, 2019; Bale, 2018; Fairhurst, 2016; Kümler, 2015; Rangarajan, 2023; Seidensticker, 2015; Vogl, 2023; Xiao, 2018).

Liver metastasis from uveal melanoma

Up to 90% of individuals with metastatic uveal melanoma develop liver metastases, often as the dominant or initial site of spread. In this setting, the NCCN CPG (V2.2025) for uveal melanoma note that liver-directed therapies, including local thermal ablation, RFA, MWA or cryotherapy, may be considered in highly selected individuals with limited hepatic disease. These interventions are described as palliative or disease-control measures, not curative therapies, and are generally considered when complete treatment of all visible liver lesions is technically feasible. The supporting evidence is limited to retrospective, nonrandomized studies, and that no prospective randomized trials have demonstrated an improvement in overall or progression-free survival with ablative therapies in metastatic uveal melanoma. Local ablative therapies are not considered standard of care, and systemic therapy or clinical trial enrollment remains preferred.

Liver metastasis from other primary sites

Evidence regarding the use of local thermal ablative therapies to treat liver metastases from other primary sites is limited. There is a lack of studies evaluating these therapies. The studies which do exist as limited by study design and size. The NCCN does not recommend local ablation for other metastatic tumors to the liver.

Intrahepatic Cholangiocarcinoma (CCA)

CCAs are tumors originating in the epithelium of the bile ducts and can be classified as intrahepatic or extrahepatic tumors. Extrahepatic tumors are more common than intrahepatic tumors, but the incidence of intrahepatic tumors has increased more quickly than extrahepatic tumors. Intrahepatic CCAs are often diagnosed at a late stage due to the nonspecific symptoms associated with early-stage disease. Surgical resection is considered the only potentially curative treatment although most individuals are not candidates for surgical resection at the time of diagnosis (NCCN, V2.2025). At the time of diagnosis, approximately 15 to 30% of individuals are considered to have surgically resectable disease (Mosconi, 2021). For individuals with unresectable disease, the NCCN recommends various potential locoregional options including arterially directed therapy. The studies supporting this recommendation consist primarily of smaller, retrospective studies. Due to the relative rarity of intrahepatic CCA, larger randomized studies may not be feasible (Mosconi, 2021).

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; Lee, 2020).

Bridge therapy is typically recommended when predicted liver transplant times are likely to exceed 6 months. The majority of studies include a combination of therapies rather than a sole therapy. A number of locoregional therapies have been recognized as successful bridging techniques to maintain transplant eligibility and there is no evidence to support the superiority of any one technique in those studied. In those individuals who are able to achieve a complete response from locoregional therapy prior to transplant, bridging therapy may improve post-transplant survival (Agopian, 2017; Braat, 2016; Bauschke, 2020; Cheng, 2005b; Kulik, 2018; Lee, 2017; Lewandowski, 2009; Obed, 2007).

The current Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) liver allocation policy relies on Model for End-Stage Liver Disease (MELD, for candidates ≥ 12 years) and Pediatric End-Stage Liver Disease (PELD, for children < 12 years) to prioritize transplant candidates. For hepatocellular carcinoma (HCC), standardized MELD/PELD exception points are available when candidates meet defined criteria (historically aligned with T2/Milan criteria) and remain within those criteria over time. To qualify for and maintain these exceptions, transplant programs routinely document loco-regional therapies and imaging, which effectively recognizes a role for loco-regional therapy in the pre-transplant setting. This framework influences clinical management of tumors on the wait list but does not explicitly mandate or “incentivize” specific treatments within the policy text. The MELD score is a continuous disease severity scale incorporating serum bilirubin, prothrombin time (for example, 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:

• One lesion greater than or equal to 2 cm and less than or equal to 5 cm; or,
• Two or three lesions each greater than or equal to 1 cm and less than or equal to 3 cm in size.

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 CPG for hepatocellular carcinoma (V2.2025) addresses the use of locoregional therapies, including ablative techniques noting:

Bridge therapy is used to decrease tumor progression and the dropout rate from the liver transplantation waiting list. It is also an effective way to help select the best patients for transplant and is recommended for patients who meet transplant criteria… A number of studies have investigated the role of locoregional therapies as a bridge to liver transplantation in patients on a waiting list.

Limitations of these studies include size and heterogeneity of the study populations; however, the NCCN CPG states, “Nevertheless, the use of bridge therapy in this setting is increasing, and it is administered at most NCCN Member Institutions, especially in areas where there are long wait times for a transplant.”

The 2023 AASLD guidelines on HCC (Singal, 2023) include locoregional therapy (LRT) recommendations for bridging therapy:

• AASLD advises the use of pre-transplant locoregional bridging therapy for patients being evaluated or listed for liver transplantation, if they have adequate hepatic reserve, to reduce the risk of waitlist dropout in the context of anticipated prolonged wait times for transplant (Level 3, Strong Recommendation).
• AASLD does not advise one LRT over another for bridging therapy. The choice of locoregional modality should be based on tumor size, location, and center expertise (Level 3, Weak Recommendation).

Hepatocellular Carcinoma in Individuals Who May Become Eligible for Liver Transplantation

Downstaging therapy is defined as treatment used to reduce the tumor burden in individuals without distant metastasis but do have more advanced HCC whose tumor characteristics are beyond the accepted transplant criteria (NCCN, V2.2025). The choice of technique used is influenced by multiple factors, such as tumor size/number, location, liver function, and individual center experience (Kulik, 2018).

In a 2020 retrospective study, Lee evaluated the long-term outcomes of individuals who underwent liver transplantation with or without downstaging or bridging therapy. Individuals with HCC without extrahepatic metastasis who underwent TACE (n=409), RFA (n=50), resection (n=13) radiation (n=5) or combination therapy (n=211) treatment were included in the review. An individual was considered to achieve a successful downstaging (SD) when there was a reduction in the number and size of viable tumors to within the Milan criteria. SD outcomes were associated with improved recurrence-free survival (RFS) and OS when compared to those who experience downstaging failure or disease progression. Individuals with SD prior to liver transplantation achieved better RFS when compared to individuals who did not undergo downstaging prior to liver transplantation.

Yao and associates (2015) compared the long-term outcomes of individuals with HCC who underwent downstaging to prior to liver transplantation (n=118) to individuals who did not require downstaging prior to liver transplantation (n=488). Tumor downstaging was not successful in 41 individuals (34.7%). Individuals who underwent successful downstaging achieved similar Kaplan-Meier 1- and 5-year post-transplant survival compared to those who did not undergo downstaging (93.4% and 77.8% vs. 94.3% and 81%, respectively; p=0.69). While the study did include individuals with 4-5 lesions (n=14), the size of this group precludes drawing firm conclusions about the efficacy of downstaging in this subgroup. The authors reported successful post-transplant outcomes following downstaging but noted “We believe that there are upper limits in tumor size and number beyond which down-staging is not likely to be successful and the outcome may be significantly worse.”

The NCCN CPG for hepatocellular cancers (V2.2025), principles of surgery, includes the following recommendation:

Patients meeting the UNOS criteria [(AFP level ≤1000 ng/mL and single lesion ≥2cm and ≤5 cm, or 2 or 3 lesions ≥1cm and ≤3cm)] should be considered for transplantation (cadaveric or living donation).

The Model for End-Stage Liver Disease (MELD) score is used by UNOS to assess the severity of liver disease and prioritize the allocation of the liver transplants… There are patients whose tumor characteristics are marginally outside of the UNOS guidelines who should be considered for transplant. Furthermore, there are patients who are downstaged to within criteria that can also be considered for transplantation.

The 2025 OPTN and UNOS allocation policy notes that lesions which are eligible for downstaging protocols must meet one of the following criteria:

1. One Class 5 lesion greater than 5 cm and less than or equal to 8 cm
2. Two or three Class 5 lesions that meet all of the following:
   • at least one lesion greater than 3 cm
   • each lesion less than or equal to 5 cm, and
   • a total diameter of all lesions less than or equal to 8 cm
3. Four or five Class 5 lesions each less than 3 cm, and a total diameter of all lesions less than or equal to 8 cm

For individuals who have met the downstaging criteria and subsequently undergo local-regional therapy, any residual therapy must meet the definition for T2 lesions in order to be eligible for a standardized MELD or PELD exception.

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.

Adenocarcinoma: Cancer which arises from glandular epithelial cells within internal organs. The majority of breast, lung, esophagus, stomach, colon, rectum, pancreas, prostate, and uterus cancers are classified as adenocarcinomas.

Bridge Therapy: Therapy considered for those who meet transplant criteria, used slow tumor progression in order to decrease the liver transplantation dropout rate.

Childs-Turcotte-Pugh (CTP): A scoring system for severity of liver disease and likelihood of survival based on the presence of: degenerative disease of the brain (encephalopathy), the escape or accumulation of fluid in the abdominal cavity (ascites), laboratory measures of various substances in the blood (see table below), and the presence of other co-existing diseases; after calculating the CTP score using a table similar to the one below, candidates can be classified into 1 of 3 categories:

• Childs A (5-6 points): 10 year survival 80-90%
• Childs B (7-9 points): 5 year survival 60-80%
• Childs C (10-15 points): 2 year survival less than 50%

Cancer of the Liver Italian Program (CLIP): A tumor classification system from Italy that includes scoring for 8 clinical parameters for HCC, combining the Child-Turcotte-Pugh scoring system with tumor criteria including tumor morphology, portal invasion, and alpha fetoprotein levels.

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

Encapsulated nodules: Any group of abnormal cells confined to a specific area, surrounded by a covering of specialized cells called a capsule.

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.

Palliative treatment: Treatment given for relief of symptoms and pain rather than effecting a cure.

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.

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, 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.
3. Agopian VG, Harlander-Locke MP, Ruiz RM, et al. Impact of pretransplant bridging locoregional therapy for patients with hepatocellular carcinoma within Milan criteria undergoing liver transplantation: analysis of 3601 patients from the US Multicenter HCC Transplant Consortium. Ann Surg. 2017; 266(3):525-535.
4. Arora S, Harmath C, Catania R, et al. Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings. Abdom Radiol (NY). 2021; 46(8):3698-3707.
5. 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.
6. Bai XM, Yang W, Zhang ZY, et al. Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer. Int J Hyperthermia. 2019; 35(1):183-193.
7. Bale R, Richter M, Dünser M, et al. Stereotactic radiofrequency ablation for breast cancer liver metastases. J Vasc Interv Radiol. 2018 Feb;29(2):262-267.
8. Bauschke A, Altendorf-Hofmann A, Ardelt M, et al. Impact of successful local ablative bridging therapy prior to liver transplantation on long-term survival in patients with hepatocellular carcinoma in cirrhosis. J Cancer Res Clin Oncol. 2020; 146(7):1819-1827.
9. Berber E, Felsher N, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastasis. World J Surg. 2002; 26(8):985-990.
10. 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.
11. Berber E, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases. Problems in General Surgery. 2003; 20(3):134-142.
12. 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.
13. 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.
14. Burkhard-Meier A, Grube M, Jurinovic V, et al. Unraveling the role of local ablative therapies for patients with metastatic soft tissue sarcoma - a retrospective multicenter study of the Bavarian university hospitals. Eur J Surg Oncol. 2024; 50(12):108619.
15. Cassera MA, Hammill CW, Ujiki MB, et al. Surgical management of breast cancer liver metastases. HPB (Oxford). 2011; 13(4):272-278.
16. Charalampoudis P, Mantas D, Sotiropoulos GC, et al. Surgery for liver metastases from breast cancer. Future Oncol. 2015; 11(10):1519-1530.
17. Cheng BQ, Jia CQ, Liu CT, et al. Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. JAMA. 2008; 299(14):1669-1677.
18. Chlorogiannis DD, Sotirchos VS, Georgiades C, et al. The importance of optimal thermal ablation margins in colorectal liver metastases: a systematic review and meta-analysis of 21 studies. Cancers (Basel). 2023; 15(24):5806.
19. 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.
20. Chong CCN, Lee KF, Cheung SYS, et al. Prospective double-blinded randomized controlled trial of microwave versus radiofrequency ablation for hepatocellular carcinoma (McRFA trial). HPB (Oxford). 2020; 22(8):1121-1127.
21. 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.
22. 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.
23. Efthymiou E, Charalampopoulos G, Velonakis G, et al. Ablative techniques for sarcoma metastatic disease: current role and clinical applications. Medicina (Kaunas). 2023; 59(3):485.
24. 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.
25. Fan H, Zhou C, Yan J, et al. Treatment of solitary hepatocellular carcinoma up to 2 cm: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2020; 99(23):e20321.
26. 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.
27. 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.
28. 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.
29. Fisher RA, Maluf D, Cotterell AH, et al. Non-resective ablative therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list. Clin Transplant. 2004; 18(5):502-512.
30. Georgiades CS, Ramsey DE, Solomon S, et al. New non-surgical therapies in the treatment of hepatocellular carcinomas. Tech Vasc Intervent Radiol. 2001; 4(3):193-199.
31. 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.
32. Gootjes EC, van der Stok EP, Buffart TE, et al.; ORCHESTRA study group. Safety and feasibility of additional tumor debulking to first-line palliative combination chemotherapy for patients with multiorgan metastatic colorectal cancer. Oncologist. 2020; 25(8):e1195-e1201.
33. Gronchi A, Guadagnolo BA, Erinjeri JP. Local ablative therapies to metastatic soft tissue sarcoma. Am Soc Clin Oncol Educ Book. 2016;35:e566-75.
34. 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.
35. 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.
36. Kamal A, Elmoety AAA, Rostom YAM, et al. Percutaneous radiofrequency versus microwave ablation for management of hepatocellular carcinoma: a randomized controlled trial. J Gastrointest Oncol. 2019; 10(3):562-571.
37. Karanicolas P, Beecroft JR, Cosby R, et al.; Gastrointestinal Disease Site Group. Regional therapies for colorectal liver metastases: systematic review and clinical practice guideline. Clin Colorectal Cancer. 2021; 20(1):20-28.
38. Katsanos K, Kitrou P, Spiliopoulos S, et al. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: a network meta-analysis of randomized controlled trials. PLoS One. 2017; 12(9):e0184597.
39. Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy - an intergroup study. J Clin Oncol. 2002; 20(6):1499-1505.
40. Kivelä T, Eskelin S, Kujala E. Metastatic uveal melanoma. Int Ophthalmol Clin. 2006; 46(1):133-149.
41. Knüppel M, Kubicka S, Vogel A, et al. Combination of conservative and interventional therapy strategies for intra- and extrahepatic cholangiocellular carcinoma: a retrospective survival analysis. Gastroenterol Res Pract. 2012; 2012:190708.
42. Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology. 2018; 67(1):381-400.
43. 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.
44. 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.
45. Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int. 2008; 7(3):237-257.
46. Lee S, Kim KW, Song GW, et al. The real impact of bridging or downstaging on survival outcomes after liver transplantation for hepatocellular carcinoma. Liver Cancer. 2020; 9(6):721-733.
47. Lee MW, Raman SS, Asvadi NH, et al. Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: a 10-year intention-to-treat analysis. Hepatology. 2017; 65(6):1979-1990.
48. 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.
49. 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.
50. Li XP, Meng ZQ, Guo WJ, Li J. Treatment for liver metastases from breast cancer: results and prognostic factors. World J Gastroenterol. 2005; 11(24):3782-3787.
51. 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.
52. Liu W, Bahig H, Palma DA. Oligometastases: emerging evidence. J Clin Oncol. 2022; 40(36):4250-4260.
53. Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000; 214(3):761-768.
54. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: treatment with radiofrequency ablation versus ethanol injection. Radiology. 1999; 210(3):655-661.
55. Llovet JM. Evidence-based medicine in the treatment of hepatocellular cancer. J Gastroenterol Hepatol. 2002a; 17 Suppl 3:S428-S433.
56. Llovet JM, Di Bisceglie AM, Bruix J, et al. Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008; 100(10):698-711.
57. Llovet JM, Fuster J, Bruix J. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004; 10(2 Suppl 1):S115-S120.
58. 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.
59. Majno P, Giostra E, Mentha G. Management of hepatocellular carcinoma on the waiting list before liver transplantation: time for controlled trials? Liver Transpl. 2007; 13(11 Suppl 2):S27-S35.
60. 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.
61. 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.
62. Meijerink MR, Puijk RS, van Tilborg AAJM, et al. Radiofrequency and microwave ablation compared to systemic chemotherapy and to partial hepatectomy in the treatment of colorectal liver metastases: a systematic review and meta-analysis. Cardiovasc Intervent Radiol. 2018; 41(8):1189-1204.
63. 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.
64. Merli M, Nicolini G, Gentilli F, et al. Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma. Transplant Proc. 2005; 37(6):2535-2540.
65. 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.
66. 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.
67. Peng ZW, Liu FR, Ye S, et al. Radiofrequency ablation versus open hepatic resection for elderly patients (> 65 years) with very early or early hepatocellular carcinoma. Cancer. 2013; 119(21):3812-3820.
68. 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.
69. Peng ZW, Zhang YJ, Liang HH, et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2010; 262(2):689-700.
70. 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.
71. Rangarajan K, Lazzereschi L, Votano D, Hamady Z. Breast cancer liver metastases: systematic review and time to event meta-analysis with comparison between available treatments. Ann R Coll Surg Engl. 2023; 105(4):293-305.
72. Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019; 29(6):561-568.
73. Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008; 8(12):2547-2557.
74. Roayaie S, Frischer J, Emre SH, et al. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg. 2002; 235(4):533-539.
75. Ruers T, Van Coevorden F, Punt CJ, et al.; European Organisation for Research and Treatment of Cancer (EORTC); Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst. 2017; 109(9):djx015.
76. 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.
77. 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.
78. Sauer P, Kraus TW, Schemmer P, et al. Liver transplantation for hepatocellular carcinoma: is there evidence for expanding the selection criteria? Transplantation. 2005; 80(1 Suppl):S105-S108.
79. 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.
80. Shady W, Petre EN, Do KG, et al. Percutaneous microwave versus radiofrequency ablation of colorectal liver metastases: ablation with clear margins (A0) provides the best local tumor control. J Vasc Interv Radiol. 2018; 29(2):268-275
81. Shen A, Zhang H, Tang C, et al. Systematic review of radiofrequency ablation versus percutaneous ethanol injection for small hepatocellular carcinoma up to 3 cm. J Gastroenterol Hepatol. 2013; 28(5):793-800.
82. Siebenhüner AR, Güller U, Warschkow R. Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases. BMC Cancer. 2020; 20(1):246.
83. 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.
84. Stewart CL, Warner S, Ito K, et al. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg. 2018; 55(9):330-379.
85. 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.
86. 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.
87. Tateishi R, Shiina S, Teratani, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1000 cases. Cancer. 2005; 103(6):1201-1209.
88. Tovoli F, Negrini G, Bolondi L. Comparative analysis of current guidelines for the treatment of hepatocellular carcinoma. Hepat Oncol. 2016; 3(2):119-136.
89. Uggeri F, Pinotti E, Sandini M, et al. Prognostic factors affecting long-term survival after resection for noncolorectal, nonneuroendocrine, and nonsarcoma liver metastases. Gastroenterol Res Pract. 2017; 2017:5184146.
90. Uggeri F, Ronchi PA, Goffredo P, et al. Metastatic liver disease from non-colorectal, non-neuroendocrine, non-sarcoma cancers: a systematic review. World J Surg Oncol. 2015; 13:191.
91. 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.
92. Vietti Violi N, Duran R, et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2018; 3(5):317-325.
93. Vogl TJ, Freichel J, Gruber-Rouh T, et al. Interventional oncological treatment of breast cancer liver metastasis (BCLM): single center long-term evaluation over 26 years using thermoablation techniques like LITT, MWA and TACE in a multimodal application. Int J Hyperthermia. 2023; 40(1):2200582.
94. Vouche M, Habib A, Ward TJ, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014; 60(1):192-201.
95. Wang C, Song L, Wang Z, Wang W. The application of radiofrequency ablation in pancreatic cancer liver-only recurrence after radical pancreatectomy. Med Oncol. 2023; 40(7):209.
96. Wang LT, Yang J, Wu J, Lu WJ. Combined therapy of chemotherapy and radiofrequency ablation for pancreatic cancer patients with metachronous hepatic metastatic lesions after radical pancreatic resection. Cancer Control. 2024; 31:10732748241274559.
97. Xiang J, Liu M, Lu R, et al. Magnetic resonance-guided ablation of liver tumors: a systematic review and pooled analysis. J Cancer Res Ther. 2020; 16(5):1093-1099.
98. Xiao YB, Zhang B, Wu YL. Radiofrequency ablation versus hepatic resection for breast cancer liver metastasis: a systematic review and meta-analysis. J Zhejiang Univ Sci B. 2018; 19(11):829-843.
99. Yamashiki N, Tateishi R, Yoshida H, et al. Ablation therapy in containing extension of hepatocellular carcinoma: a simulative analysis of dropout from the waiting list for liver transplantation. Liver Transpl. 2005; 11(5):508-514.
100. Yao FY, Bass NM, Nikolai B, et al. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl. 2003; 9(7):684-692.
101. Yao FY, Kerlan RK Jr, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008; 48(3):819-827
102. Yao FY, Kinkhabwala M, LaBerge JM, et al. The impact of pre-operative locoregional therapy on outcome after liver transplantation for hepatocellular carcinoma. Am J Transplant. 2005; 5(4 Pt 1):795-804.
103. Yao FY, Mehta N, Flemming J, e al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015; 61(6):1968-1677.
104. Yu J, Yu XL, Han ZY, et al. Percutaneous cooled-probe microwave versus radiofrequency ablation in early-stage hepatocellular carcinoma: a phase III randomised controlled trial. Gut. 2017 Jun;66(6):1172-1173.
105. Yue YY, Zhou WL. Hepatic resection is associated with improved long-term survival compared to
106. radio-frequency ablation in patients with multifocal hepatocellular carcinoma. Front Oncol. 2020; 10:110.
107. 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.
108. 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.
109. 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.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Radiology. ACR Appropriateness criteria^®. management of liver cancer. Last review date 2022. Available at: https://acsearch.acr.org/docs/69379/Narrative/. Accessed on January 21, 2026.
2. Bala MM, Riemsma RP, Wolff R, Kleijnen J. Cryotherapy for liver metastases. Cochrane Database Syst Rev. 2013;(6):CD009058.
3. Bala MM, Riemsma RP, Wolff R, Kleijnen J. Microwave coagulation for liver metastases. Cochrane Database Syst Rev. 2013;(10):CD010163.
4. 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.
5. 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.
6. 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.
7. 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.
8. Expert Panel on Interventional Radiology; Knavel Koepsel EM, Smolock AR, et al. ACR appropriateness criteria^® management of liver cancer: 2022 update. J Am Coll Radiol. 2022; 19(11S):S390-S408.
9. 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.
10. 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.
11. 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.
12. Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018; 67(1):358-380.
13. Hong K, Akinwande O, Bodei L, et al. ACR-ABS-ACNM-ASTRO-SIR-SNMMI practice parameter for selective internal radiation therapy or radioembolization for treatment of liver malignancies. Brachytherapy. 2021; 20(3):497-511.
14. Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology. 2018; 67(1):381-400.
15. Kutlu OC, Chan JA, Aloia TA, et al. Comparative effectiveness of first-line radiofrequency ablation versus surgical resection and transplantation for patients with early hepatocellular carcinoma. Cancer. 2017; 123(10):1817-1827.
16. Lievens Y, Guckenberger M, Gomez D, et al. Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document. Radiother Oncol. 2020; 148:157-166.
17. Marrero JA, Ahn J, Rajender Reddy K; American College of Gastroenterology. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014; 109(9):1328-47.
18. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018; 68(2):723-750.
19. National Comprehensive Cancer Network^® (NCCN) Practice Guidelines in Oncology^™. ^© 2026 National Comprehensive Cancer Network, Inc. For additional information, visit the NCCN website: http://www.nccn.org. Accessed on January 15, 2026.
    • Biliary Tract Cancers (V2.2025). Revised July 2, 2025.
    • Breast Cancer (V1.2026). Revised January 16, 2026.
    • Colon Cancer (V5.2025). Revised October 30, 2025.
    • Gastrointestinal Stromal Tumors (V1.2026). Revised January 13, 2026.
    • Hepatocellular Carcinoma (V2.2025). Revised October 22, 2025.
    • Kidney Cancer (V1.2026). Revised July 25, 2025.
    • Melanoma: Uveal (V2.2025) Revised November 6, 2025.
    • Neuroendocrine and Adrenal Tumors (V3.2025). Revised October 1, 2025.
    • Occult Primary (Cancer of Unknown Primary [CUP]. (V1.2026). Revised October 21, 2025.
    • Pancreatic Adenocarcinoma (V2.2025). Revised February 3, 2025.
    • Rectal Cancer (V4.2025). Revised October 31, 2025.
    • Soft Tissue Sarcoma (V1.2026). Revised January 16, 2026.
    • Thymomas and Thymic Carcinoma (V1.2026). Revised October 2, 2025.
20. Organ Procurement and Transplantation Network. United Network for Organ Sharing (UNOS). Policy: 9 allocation of livers and liver-intestines. Effective December 10, 2025. Available at: http://optn.transplant.hrsa.gov/governance/policies/. Accessed on January 20, 2026.
21. Perez K, Del Rivero J, Kennedy EB, et al. Symptom management for well-differentiated gastroenteropancreatic neuroendocrine tumors: ASCO guideline. JCO Oncol Pract. 2025: OP2500133.
22. Riemsma RP, Bala MM, Wolff R, Kleijnen J. Electro-coagulation for liver metastases. Cochrane Database Syst Rev. 2013;(5):CD009497.
23. Singal AG, Llovet JM, Yarchoan M, et al. AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023; 78(6):1922-1965.
24. Swierz MJ, Storman D, Riemsma RP, et al. Percutaneous ethanol injection for liver metastases. Cochrane Database Syst Rev. 2020; 2(2):CD008717.
25. 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.
26. 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.
27. 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.

1. American Cancer Society. Available at: www.cancer.org. Accessed on February 1, 2026.
2. National Cancer Institute. Cancer topics Available at: http://www.cancer.gov/cancertopics. Accessed on February 1, 2026.
   • Adult Primary Liver Cancer (PDQ^®): Treatment. Last updated April 17, 2025.
   • Childhood Liver Cancer Treatment (PDQ). Last updated January 6, 2025.
   • Colon Cancer Treatment (PDQ). Last updated February 12, 2025.
   • Gastrointestinal Neuroendocrine Tumors (PDQ). Last updated May 9, 2025.
   • Intraocular (Uveal) Melanoma Treatment (PDQ). Last updated May 16, 2025.
   • Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ). Last updated May 9, 2025.
   • Rectal Cancer Treatment (PDQ). Last updated February 12, 2025.

Colorectal Cancer
Cryoablation
Hepatic Metastases
Hepatic Tumors
Hepatocellular Carcinoma
Liver Tumors
Metastatic Liver Tumors
Microwave Ablation
Percutaneous Ethanol Injection (PEI)
Radiofrequency Ablation (RFA)
Surgical Ablation

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