Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

What is the comparative effectiveness of various local treatments for (1) unresectable liver metastases and (2) unresectable, localized hepatocellular carcinoma (HCC)? Does the comparative effectiveness vary when lesions are unresectable due to anatomic reasons compared to those that are unresectable due to patients’ comorbid illness?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

A number of interventions have been used, both individually and more recently in combination for treatment of these conditions. These include the following: Hepatic artery infusion chemotherapy TACE (transarterial chemoembolization) TAE (transarterial embolization) Radioembolization (radioactive spheres) Drug-eluting beads Radiofrequency ablation Cryoablation Radiation therapy including stereotactic body radiotherapy

Percutaneous ethanol injection (PEI) has also been used in the past to treat HCC.

Treatment as a bridge to liver transplantation or to downstage tumor prior to transplantation also has a key role in the treatment of some patients with HCC.

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

In general, these patients are middle-aged or older. As such, they may have a number of comorbid illnesses which can impact treatment choices. The presence of coexisting liver impairment can further complicate the decisions about treatment. The need to fully understand relative risks and benefits is key in this clinical situation.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Important subgroups are based on the reasons that lesions are not resectable; that is, those whose disease is not resectable due to anatomic reasons and those whose lesions are unresectable due to comorbid illness (i.e., the patient is not an operative candidate).

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Patient survival, quality of life, and palliation of symptoms.

Describe any health-related risks, side effects, or harms that you are concerned about.

Treatment toxicity and complications of the procedure.

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cancer

AHRQ Priority Populations

• Elderly

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

Treatment of unresectable hepatic (liver) metastases, especially those whose metastatic disease appears confined to the liver is a common problem for cancer patients. (Surgical resection, when possible, is considered the preferred approach. Surgical resection with clean margins or liver transplantation (for HCC) is the only treatments available with demonstrated curative potential. However, the majority of hepatic tumors are unresectable at diagnosis.) This clinical scenario occurs frequently in patients with colorectal cancer. It may also occur with other common tumors such as breast cancer. Patients with neuroendocrine tumors may develop severe symptoms, due to local disease and systemic effects, from hepatic metastases. While there are multiple interventions that can be utilized in treatment, the comparative effectiveness is not known. Thus, there is great uncertainty about the optimal approach to these patients. In addition, new techniques, such as stereotactic body radiotherapy (SBRT) are being evaluated and combinations of treatments are evolving.

In studying relative risks and benefits, it will likely be important to factor in the reason a tumor is unresectable. Patients with unresectable tumors due to anatomic reasons (e.g. location of the tumor) may have different outcomes that those whose tumors are unresectable because comorbid illness precludes a standard surgical approach.

In evaluating the comparative effectiveness in metastatic disease, it is critical to evaluate patient-related outcomes and not focus only on liver-related outcomes. This is necessary because in these patients metastatic disease may develop in other parts of the body and the overall impact of treating the liver may be unknown.

While not as common, hepatocellular carcinoma (HCC) is an important clinical condition, in part through its linkage with chronic hepatitis. The comparative effectiveness of the various treatments noted above is important. In addition, t

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

BlueCross and BlueShield Plans have used an evidence-based approach to medical policy for over twenty years. In reviewing evidence related to these two clinical conditions, while various technologies have been utilized there is a need to understand the comparative effectiveness of these many alternatives. Patients need to understand the relative benefits and risks of these interventions, whether done as individual therapies or done as combined therapy.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

It is uncertain if one or more of these technologies is the best choice for specific types of patients. The role of these various therapies in those whose lesions are unresectable due to serious comorbid illness is a question of particular interest.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

BlueCross BlueShield Plan Medical Directors will use the results in the development of medical policies.

Describe the timeframe in which an answer to your question is needed.

Approximately 18 months.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Not applicable

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

BlueCross BlueShield Plan Medical Directors will use the results in the development of medical policies.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

BlueCross BlueShield Plans routinely use information issued by the EHC. The BlueCross BlueShield association Technology Evaluation Center is an Evidence-based Practice Center of AHRQ. BCBS EPC staff were consulted in the preparation of this nomination. This topic nomination was based on input from the BlueCross BlueShield Plan Medical Directors.