The liver is the most common site for systemic spread of CRC.
- Approximately 50% of patients eventually develop liver metastases over the course of the disease
- Approximately 20% to 25% of the metastases will be surgically resectable1
- Staging work-up may include a CT scan of the chest, abdomen and pelvis
- When liver metastases are found, the course of treatment may include
- Neoadjuvant chemotherapy to reduce tumor bulk
- Surgical resection of the primary tumor and liver metastases, if resectable
- Postoperative chemotherapy to provide systemic control2,3
- Liver resection remains the gold standard for treatment of resectable liver metastases
- Several local destruction methods may reduce the size of the liver metastases, possibly rendering them resectable, or to reduce the risk of local recurrence3
Methods of local ablation include:
Hepatic arterial infusion (HAI)
Radiofrequency ablation (RFA)
Chemoembolization or portal vein embolization
Hepatic arterial infusion (HAI) selectively delivers high-dose chemotherapy to the liver. It is generally administered in a 14- to 21-day infusion, intermittent or continuous, using one of the following chemotherapy agents:
Fluorodeoxyuridine (FUDR) with or without dexamethasone4
CT angiography helps identify the hepatic artery, and an implanted port is surgically placed in the gastroduodenal artery for infusion of the chemotherapy. A benefit of HAI is that local drug administration minimizes systemic drug exposure and side effects. Risks associated with HAI include:
- HAI of FUDR can damage bile ducts3
- Catheter-related complications (blockage and/or infection)
- Localized hepatic toxicity5
- Chemical hepatitis
- Hyperbilirubinemia (> 3 mg/dL)
- Generally normalizes within 1 month after treatment is completed
- Persistent hyperbilirubinemia may require biliary stents6
FUDR, the most commonly used HAI chemotherapeutic agent, has the following reported side effects7:
Gastrointestinal (anorexia, diarrhea, abdominal cramping and pain, stomatitis)
Neurologic (paresthesia or tingling in hands and/or feet)
Myelosuppression (neutropenia, thrombocytopenia)
In a randomized comparative study, Kemeny and coworkers reported
- Slightly better overall survival with HAI (24.4 months) compared with systemic therapy (20.2 months)
- 2-year survival of 51% versus 35% systemic
- Control group used the Mayo regimen and outcomes may be different when tested against newer therapies6
Radiofrequency ablation (RFA) uses energy waves to heat cancer cells.
- Cells are heated, coagulation necrosis and subsequent cell destruction occurs ablating the tumor
- Procedure performed using a percutaneous (through the skin) approach with an endoscope, or by laparoscopy8
- Ultrasound or CT guidance guides the surgeon to the area(s) of metastatic disease
In selecting patients for RFA, the Rule of Fives9 has been suggested to limit the use of RFA to patients for whom it would be most appropriate:
- < 5 cm diameter tumor
- < 5 hepatic metastatic sites
RFA can be used as an
- Adjunct to surgical resection with positive margins of resectable metastases or to reduce the size of nonresectable metastases
A prospective, randomized trial to determine predictors of survival at the time of RFA in patients with metastatic CRC found
- Tumor size = 5 cm carries a 2.5 times increased risk of death versus tumor size < 3 cm10
Hepatic cryotherapy, the freezing and thawing of liver tumors with a cryoprobe, is inserted into the tumors.
- Freeze-thaw cycles, intracellular and extracellular ice formation occurs, leading to tumor destruction
- Hepatic cryotherapy, generally reserved for CRC patients with liver metastases, is one or more lesions not surgically resectable
- Cryotherapy also used to treat patients left with a positive surgical margin after hepatic resection or in patients where underlying illness or hepatic insufficiency precludes surgical resection11
Metastases are localized by ultrasonography, accessed by laparotomy
- Metastases frozen using cryosurgical equipment, resulting in necrosis of the tumor
- Advances in cryotherapy;
- Feasibility and safety well accepted
- New or improved liquid nitrogen delivery systems
- Intraoperative ultrasound
- Low mortality and acceptable morbidity
- Experience with cryosurgery limited, but promising results
- Studies report a 1-year survival of more than 70%
- 2-year survival of > 50%
- Disease-free survival after 2 years varies between 20% and 29%12
- Long-term survival unclear
- Hepatic cryotherapy an option for patients not candidates for surgical resection12
Chemoembolization/Portal Vein Embolization
Embolization, the process of injecting a foreign substance into a tumor, stops the blood flow.
- Lack of blood supply deprives the tumor of needed oxygen and nutrients causing cell death
- Chemoembolization uses small pieces of material that have been saturated with chemotherapy drugs
- Blood flow has stopped, the tumor is exposed to high concentration of drugs for a prolonged period of time
- Preoperative portal vein embolization causes hypertrophy in normal liver tissue
- Decreases probably of liver insufficiency after extensive liver resection to remove metastatic disease
- May be performed either by ultrasound-guided percutaneous puncture of a portal vein radical or by operative exposure of an ileocolic vein to access the portal vein
- Portal vein embolization is well tolerated11
- Geoghegan JG. Scheele J. Treatment of colorectal liver metastases. Br J Surg. 1999;86:158-169.
- Fong Y. Hepatic colorectal metastasis: current surgical therapy, selection criteria for hepatectomy, and role for adjuvant therapy. Adv Surg. 2000;34:351-358.
- Leonard GD, Brenner B, Kemeny NE. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005;23:2038-2048.
- Kemeny NE. Hepatic artery infusion of chemotherapy as management of hepatic metastases from colorectal cancer. Cancer J. 2002; (suppl 1):S80-S88.
- Guthoff I, Lotspeich E, Fester C et al. Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: oxaliplatin pharmarcokinetics and feasability. Anticancer Res. 2005;23:5203-5208.
- Kemeny, NE, Niedzwiecki D, Hollis DR et al. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol. 2006;24:1395-1403.
- Wilkes GM. Pocket Guide to Colorectal Cancer. Boston: Jones and Bartlett; 2005.
- Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818-827.
- Poston GJ. Radiofrequency ablation of colorectal liver metastases: where are we really going? [editorial]. J Clin Oncol. 2005;23:1342-1344.
- 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;23:1358-1364.
- Fusai G, Davidson BR. Management of colorectal liver metastases. Colorectal Dis. 2003;5:2-23.
- Neeleman N, Wobbes T, Jager GJ, et al. Cryosurgery as treatment modality for colorectal liver metastases. Hepatogastroenterology. 2001;48:325-329.