Surgical Resection

Although the prognosis for patients with metastatic CRC to the liver has been historically quite poor, advances in surgical technique have improved outcomes for patients with liver-confined metastases. In some situations, treatment of limited liver-only metastases may be curative. For example, in patients with resectable liver-only metastases, several studies have demonstrated durable long-term survival in selected patients, with 5-year survival estimates ranging between 30 percent and 58 percent.^15–21 CRC liver metastases are defined as resectable when it is anticipated that disease can be completely resected with negative margins, two adjacent liver segments can be spared, adequate vascular inflow and outflow and biliary drainage can be preserved, and adequate liver volume (20 to 25 percent) will remain postsurgery.^{22, 23} Approximately 20 to 30 percent of patients with CRC liver metastases are candidates for this approach. Some patients with lesions not well suited for resection may also receive radiofrequency ablation at the time of surgery.

In cases where patients may not have resectable liver metastases at diagnosis, systemic chemotherapy may be used to shrink the tumor and “convert” it to resectable disease.²⁴ Similar to patients with initially resectable liver metastases, these patients may also experience promising 5-year survival rates or approximately 30 percent. Hepatotoxicity from preoperative chemotherapy (e.g., steatohepatitis, sinusoidal injury) is an important concern in these patients.

Local Nonsurgical Treatment Strategies

Despite improved surgical techniques and systemic chemotherapy options, many patients may remain ineligible for resection because of anatomic constraints (tumor location or extent of metastatic lesions), inadequate hepatic functional reserve, or concurrent medical comorbidities such as poor performance status (functional impairment typically defined by a higher Eastern Cooperative Oncology Group [ECOG] grade or a lower Karnofsky score) and cardiac insufficiency.²⁵

For patients with unresectable metastatic disease, local hepatic therapy may be used in an attempt to prolong survival or to palliate symptoms (e.g., pain) in patients for whom a cure is no longer within reach. Local hepatic therapy may be used for the following care scenarios:

1. Patients with unresectable, liver-dominant metastases (i.e., majority of disease located in the liver) who are not eligible for continued systemic chemotherapy because their disease is refractory (i.e., they have experienced disease progression while on therapy). These patients generally have large-volume disease and may be offered treatment to debulk the tumor and palliate symptoms when present.²⁶ Regardless of the local hepatic therapy, patients should have liver-only metastases or liver-dominant metastases. In general, it is acceptable to have minimal extrahepatic disease (e.g., a single lung nodule) and remain a treatment candidate.
2. Patients with unresectable liver metastases at diagnosis or with limited unresectable hepatic recurrence after previous resection and who are candidates for local hepatic therapy.²⁷ In these patients, local hepatic therapies can be used as an adjunct to systemic chemotherapy with curative intent. The volume of disease in these patients is small, either in terms of lesion size or number of lesions.²⁸ These treatments are only appropriate when the entire tumor can be ablated with clear margins. To be considered a candidate for ablation or radiation therapy, patients treated in this setting should have no extrahepatic spread.

Several local hepatic therapies have been developed to treat patients with hepatic metastases of CRC. In the continuum of care, use of a local hepatic therapy may occur before or after the use of systemic chemotherapy, but it is administered most often in conjunction with systemic chemotherapy. Local hepatic therapies are divided into three groups: (1) ablation (destruction of tissue through procedures involving heating or cooling); (2) embolization (the selective blockage of blood vessels, often with agents that carry a drug to the occluded site); and (3) radiotherapy (directed radiation to destroy abnormal cells). Table 1 presents a list of the 12 interventions and their mechanisms of action, the setting in which treatment is performed, who performs the intervention, and the specific harms reported for each. The table presents these interventions grouped by type of ablation, embolization, and radiotherapy approach.

Table 1

Local nonsurgical therapies for CRC liver metastases reviewed in this report.

In patients with unresectable hepatic metastases, local hepatic therapy represents an opportunity to treat the major site of disease without exposing patients to the side effects of chronic systemic chemotherapy. Similarly, patients who have exhausted all palliative chemotherapeutic options may benefit from local hepatic therapy as a means of delaying disease progression and, in turn, delaying or preventing liver function deterioration and liver failure. Although nonsurgical local hepatic therapies are not generally considered to be curative options, selected patients may experience effective symptom palliation and, in some cases, long-term disease control.

Guidelines from the National Comprehensive Cancer Network for metastatic CRC state that ablative therapy for the metastases can be considered when all measurable metastatic disease can in fact be treated.²⁹ However, the group provides no guidance on which ablative therapy is optimal or on the comparative benefits and harms of the various palliative treatments.²⁹ A perception of clinical equipoise and limited RCT data comparing local hepatic therapies^30,31 contribute to uncertainty regarding which techniques, either alone or in combination, may be preferable for certain patient groups.