Irreversible Electroporation of Tumors Located in the Liver, Pancreas, Kidney, Lung, or Prostate

POLICY NUMBER

A.6.01.68

DESCRIPTION

Irreversible electroporation produces high-frequency electric pulses to create an electric current that permanently damages cell membranes causing cell death due to the inability to maintain homeostasis. Irreversible electroporation produces no thermal effect and appears to preserve vessels, nerves and the extracellular matrix.

Irreversible Electroporation

Electroporation generates high-frequent electric pulses between two or more electrodes which produces an electric current that damages the cell membrane and allows molecules to pass into the cell passively. Electroporation can be temporary (reversible electroporation) or permanent (irreversible electroporation or IRE). In IRE the cell membrane is permanently damaged causing cell death due to the inability to maintain homeostasis. IRE achieves its action with no thermal effect. IRE appears to preserve vessels, nerves and the extracellular matrix.

Liver Tumors

The National Cancer Institute estimates that there will be over 42,000 new cases of liver and intrahepatic bile duct cancer in 2025. Liver and intrahepatic-bile duct cancer death is the fifth most common cancer related death in males and the seventh most common in females. Approximately 75% of primary liver tumors are hepatocellular carcinoma (HCC) and the remaining cases are mostly cholangiocarcinoma (CCA). HCC is a primary liver malignant tumor that typically develops in the setting of chronic liver disease. The prognosis following diagnosis depends on several factors including tumor mass and hepatic reserve.

The main risk factor for HCC in the U.S. is non-alcoholic fatty liver disease, followed by alcoholic liver disease, and hepatitis C virus and hepatitis B virus infections. HCC is diagnosed more frequently in men than women. Asia-Pacific Islanders have higher rates of HCC compared with other racial and ethnic groups in the US. Mortality rates are higher for Native American people.

Treatment options for HCC are categorized as potentially curative surgical therapies (i.e., resection and liver transplantation) and nonsurgical therapies (liver-directed or systemic). The best long-term survival is observed after curative surgical therapies but many patients are not eligible because of tumor extent or underlying liver dysfunction. National Comprehensive Cancer Network (NCCN) guidelines for treatment of HCC state that all patients with HCC should be evaluated for potential curative therapies. For most patients with liver-isolated HCC who are not candidates for resection or transplant, liver-directed, locoregional therapies, such as ablation, are preferable to systemic therapy. Ablative strategies are potentially curative for small lesions (≤3 cm). IRE is thought to have some advantages over thermal methods of ablation, for example, the lack of “heat sink” effect from radiofrequency ablation (RFA) and the ability to treat tumors near vessels, bile ducts, and other critical structures.

Similarly for treatment of intrahepatic CCA, NCCN guidelines state that patients with intrahepatic CCA should be evaluated for potentially curative therapies (i.e., resection, ablation for lesions <3 cm). The guidelines also state that locoregional treatment such as ablation may be considered in patients who are not candidates for resection or to downstage for other treatments.

Pancreatic Cancer

Pancreatic ductal adenocarcinoma has a poor prognosis. The National Cancer Institute estimates that in 2025, there will be over 67,000 new cases of pancreatic cancer in the U.S. and over 51,000 pancreatic cancer deaths. Pancreatic cancer is the third-leading cause of cancer death in men and women.

Risk factors for developing pancreatic cancer include: cigarette smoking, obesity, alcohol use, diabetes, pancreatitis and hereditary factors.

Surgical resection is considered the only curative therapy although the majority of cases of pancreatic cancer are unresectable. Locally advanced pancreatic cancer accounts for 30% of newly diagnosed cases of pancreatic cancer and is usually unresectable due to local involvement of adjacent vessels. The 5-year overall survival rate is <5% for locally advanced, unresectable disease.

The NCCN recommended treatment for patients with locally advanced pancreatic adenocarcinoma includes systemic therapy with fluorouracil + leucovorin + irinotecan + oxaliplatin (FOLFIRINOX)-based or gemcitabine-based therapy, potentially with radiation therapy, with the goal of shrinking the tumor enough for surgical resection. Individuals who are unable to undergo surgery may continue systemic therapy. Depending on the kind of cancer and the genetic makeup some individuals may be candidates for immunotherapy or poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. Thermal (radiofrequency and microwave) ablation therapies are not commonly used due to the increased risk of trauma to the adjacent major anatomical structures. IRE is being considered as an adjunct to systemic therapy because it may not cause thermal injury to nearby sensitive structures such as the superior mesenteric and portal veins, superior mesenteric and celiac arteries, bile duct adjacent nerves, or gastrointestinal structures.

Kidney Tumors

The National Cancer Institute estimates that there will be over 80,000 new cases of kidney cancer and over 14,000 kidney cancer related deaths in 2025. At diagnosis, approximately 65% of disease is localized disease.

Kidney cancer is approximately 2-fold more common in males compared to females. Mortality rates are 2-fold higher for kidney cancers in Native American people compared to White people. There are many risk factors for kidney cancer such as smoking, hypertension, obesity, chronic kidney disease, exposure to analgesics, chemotherapy and certain toxic compounds, and kidney stones.

Surgery is curative for most patients with localized kidney cancer and is therefore the preferred treatment. NCCN guidelines for kidney cancer recommend partial or radical nephrectomy for T1 kidney cancer, or ablation or active surveillance in select patients. The guidelines say that thermal ablation is an option for the management of clinical stage T1 renal lesion that are ≤3 cm and is an option for clinical T1b masses in select patients who are not eligible for surgery. However, the guidelines caution that randomized phase III trials of ablative techniques with surgical resection have not been performed.

Lung Tumors

The National Cancer Institute estimates that there will be over 226,000 new cases of lung cancer and over 124,000 lung cancer deaths in 2025. Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death in both men and women.

Cigarette smoking is the leading risk factor for lung cancer, accounting for 80% to 90% of lung cancer deaths in the US. Other risk factors include radon exposure and radiation therapy to the chest. Black men are approximately 12% more likely to develop lung cancer than White men and Black women are approximately 16% less likely to develop lung cancer than White women. Women have historically had a lower risk than men, but the gap is closing.

The standard for treatment of stage I non–small cell lung cancer (NSCLC) in operable patients is surgical resection with lobectomy and systematic lymph node evaluation. However, a significant number of patients with stage I lung cancer are considered medically inoperable or high-risk surgical candidates. NCCN guidelines state that local ablative therapy with image-guided thermal ablation includes radiofrequency ablation, microwave ablation, and cryoablation, and may be considered for those patients who are deemed “high risk” (medically inoperable due to comorbidities) and is an option for the management of NSCLC lesions <3 cm. The guidelines also state that in the setting of progression at a limited number of sites (oligoprogression), local ablative therapy may extend the duration of benefit of the current line of systemic therapy.

Prostate Cancer

The National Cancer Institute estimates that there will be over 313,000 new cases of prostate cancer and over 35,000 prostate cancer deaths in 2025., The 5-year relative survival rate for prostate cancer is 97.9%. The most common risk factor for developing prostate cancer is increasing age. Black men are more likely to get prostate cancer compared to men of other races or ethnicities. Black men are also more than twice as likely to die from prostate cancer compared to men of other races. Genetic factors can also be a risk factor for prostate cancer, especially if a first-degree relative has had prostate cancer.

The standard for treatment of low-risk or favorable intermediate-risk prostate cancer includes active surveillance, radiation therapy, or radical prostatectomy. In patients with regional prostate cancer or higher risk groups, androgen deprivation therapy is recommended, generally in combination with radiation therapy or abiraterone. NCCN guidelines state that ablative therapy (either focal or whole gland ablative therapy) is an experimental and emerging technology for the initial treatment of localized prostate cancer that lacks randomized controlled trial evidence with long-term follow-up showing its superiority or noninferiority to current recommended management strategies. Focal therapy meets the criteria as an alternative therapy, or a non-standard treatment for initial treatment. External beam radiotherapy, brachytherapy, and cryotherapy ablation are currently US Food and Drug Administration (FDA) approved or cleared for initial treatment of prostate cancer, but randomized evidence to the superiority in long-term cancer control and/or quality of life are lacking when delivered as focal rather than whole gland therapy. Other device categories, including IRE, are noted as not currently FDA approved or cleared for the treatment of prostate cancer as focal or whole gland therapy and should only be used in the context of a clinical trial.

NCCN guidelines recommend the use of local therapy as secondary treatment in the case of biopsy-proven recurrence in the prostate after radiation therapy without distant metastatic disease. Local therapy options for patients with recurrence in the prostate include cryotherapy, IRE, high-intensity focused ultrasound, reirradation (ie, brachytherapy, sterotactic body radiotherapy), and prostatectomy plus pelvic lymph node dissection.

The NanoKnife System™ (Angiodynamics) was originally cleared through the 510(k) process (K102329) in 2011 for the surgical ablation of soft tissue. In 2024, the indication for NanoKnife was expanded to surgical ablation of soft tissue, including prostate tissue. FDA product code: OAB.

Related medical policies – 

• Catheter Ablation as Treatment for Atrial Fibrillation

• Stereotactic Radiosurgery and Stereotactic Body Radiotherapy

• Microwave Tumor Ablation

• Cryosurgical Ablation of Primary or Metastatic Liver Tumors

• Radiofrequency Ablation of Primary or Metastatic Liver Tumors

• Cryoablation of Tumors Located in the Kidney, Lung, Breast, Pancreas, or Bone

• Radiofrequency Ablation of Miscellaneous Solid Tumors Excluding Liver Tumors

• Transcatheter Arterial Chemoembolization to Treat Primary or Metastatic Liver Malignancies

• Radioembolization for Primary and Metastatic Tumors of the Liver

• Focal Treatments for Prostate Cancer

POLICY

Irreversible electroporation is considered investigational for treatment of primary or metastatic solid tumors including, but not limited to, tumors of the liver, pancreas, kidney, lung, or prostate.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Other uses of Irreversible Electroporation

Pulsed field ablation is a form of irreversible electroporation energy used to treat individuals with atrial fibrillation. Pulsed field ablation for atrial fibrillation is discussed in the Catheter Ablation as Treatment for Atrial Fibrillation medical policy.

Focal therapy with irreversible electroporation as a treatment for prostate cancer is addressed separately in the Focal Treatments for Prostate Cancer medical policy.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

04/15/2025: New policy added. Approved by the Medical Policy Advisory Committee.

01/01/2026: Code Reference section updated to add new CPT code 47384.

01/15/2026: Code Reference section updated to revise description for CPT code 0600T.

05/28/2026: Policy title updated to include tumors located in the prostate. Policy description updated regarding liver tumors, pancreatic cancer, kidney tumors, lung tumors, prostate cancer, and devices. Policy statement updated to add treatment of tumors of the prostate as investigational. Policy Guidelines updated to change "patients" to "individuals."

SOURCE(S)

Blue Cross Blue Shield Association policy # 6.01.68

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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