Interventional radiology in the management of colorectal cancer liver metastases

Colon cancer—an overview

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer, the second leading cause of cancer-related death in the United States, and recent studies estimate that 100,000 new cases of colon cancer and 40,000 of rectal cancer will occur annually. During the same time, 50,000 people will die from CRC. Within the past 30 years, the incidence of CRC has decreased from 60.5 to 46.4 per 100,000 people. Similarly CRC-related mortality has decreased by 35% in the past 15 years.

Approximately 20% of colon cancer cases are associated with familial clustering. Genetic susceptibility to colorectal cancer includes inherited syndromes such as Lynch syndrome (hereditary nonpolyposis colorectal cancer/HNPCC) and familial adenomatous polyposis (FAP). Colorectal cancer is one of the most common solid tumors and is responsible for approximately 10% of cancer-related death in the Western world. Treatment of primary colorectal cancer with surgical resection, combined with chemotherapy and radiotherapy, may be effective in many patients. About 10%–25% of patients present with synchronous liver metastases at the time of primary diagnosis and another 20%–25% of patients developed metachronous liver metastases. Surgical resection of distant CRC metastases may result in long-term survival and even cure in a subset of selected patients. The 5-year survival rates after resection of all detectable liver metastases can reach up to 40%. However, only 25% of the patients with colorectal liver metastases are candidates for liver resection, whereas the majority remain unresectable. Chemotherapy and newer therapies can extend patient survival of patients with unresectable colorectal liver metastases. Several image-guided procedures have evolved within the past 10 years that allow the management of liver metastases in nonresectable patients and those that have recurred after resection. These local therapies include local tumor ablation, hepatic arterial chemotherapy (HAC), selective internal radiation therapy (SIRT), as well as traditional arterial chemoembolization (TACE) and the more recent use of irinotecan-loaded drug-eluting beads (DEBIRI-TACE). To date, TACE and SIRT have been mostly used in patients who have failed several prior chemotherapy regimens (salvage therapies). Small randomized controlled trials showed that the addition of SIRT or DEBIRI to systemic chemotherapy result in longer disease-free and overall patient survival when compared to chemotherapy only.

In this chapter, we will elaborate on appropriate image-guided local therapies based on disease distribution and patterns. The chapter will review the indications and results of image-guided percutaneous local tumor ablation and intraarterial therapies in the management of colon cancer liver metastases (CLM).

Introduction

The natural history of CLM varies significantly based on the pattern of disease distribution. As described in a surgical review of the mid-1980s, solitary CLM, if left untreated, had survival rates of about 70% and 45% at 1 and 2 years, respectively. If the disease was widespread in one lobe or two lobes, that is, multiple unilobar or bilobar lesions, 1- and 2-year survival rates varied from 65% to 30% and 40% to 15%, respectively. Survival rates at 3 and 5 years were significantly decreased for either solitary CLM or multiple unilobar and bilobar disease to 5% or less. Thirty years later, in 2011, survival rates have dramatically improved to higher than 60% at 2 years and 35% at 5 years. This improvement is attributed to the availability of new chemotherapeutic agents along with improved imaging for early tumor detection as well as aggressive surgical debulking and locoregional therapies including image-guided interventions.

National Comprehensive Cancer Network (NCCN) guidelines emphasize the value of systemic chemotherapy in the management of CLM. Although NCCN guidelines indicate the value of surgery (or ablation) for well-selected patients, they do not endorse the widespread use of intraarterial locoregional therapies largely because of their lower level of evidence (mostly level 3, small numbers of level 2, and sparse numbers of level 1 studies). This discordance between NCCN guidelines and the 2002 FDA approval in particular for SIRT with resin microspheres for CLM stems from the fact that with the exception of a handful of small randomized controlled trials showing better progression-free survivals for the patients using SIRT in addition to chemotherapy to date, there is no large randomized controlled study conducted for loco-regional therapies to document a statistically significant overall survival benefit.

Ablation in the treatment of colorectal metastases

Ablative technologies involve the delivery of tumoricidal energy directly within the tumor in order to destroy the target tumor and a surrounding margin of normal liver while minimizing the impact on the rest of the nonaffected liver. Advantages include less physiological stress, since ablative therapies do not require open surgery but can be applied percutaneously under imaging guidance or laparoscopically.

These advantages allow the treatment of patients unfit or unwilling to undergo major abdominal surgery and those who are poor candidates for general anesthesia. Ablative therapies minimize the destruction of healthy liver tissue as compared to hepatic resection. This is an important parameter for patients with low volume of healthy functioning parenchyma such as those with underlying cirrhosis or steatohepatitis from prolonged chemotherapy exposure as well as those that have previously undergone extensive liver resection. Image-guided ablation has also been used as a salvage therapy for recurrences after prior hepatectomy. ^, The “test of time” approach using percutaneous ablation was proposed by Livraghi et al. in 2003 to allow the biology of the disease to express itself and to maintain quality of life in patients with liver metastases from colorectal cancer waiting for surgery. The concept is that many patients may be able to avoid unnecessary surgery by undergoing ablation of liver metastases while waiting for hepatic metastasectomy. In summary, this approach allows the disease to express its biology. Patients with indolent disease and a successful ablation as well as those with very aggressive and prolific disease who develop nonresectable metastases during follow-up after ablation are spared unnecessary and morbid resection. This concept offers an interesting management approach with the use of the least morbid therapy (ablation) first, in a setting that benefits the patient and monitors for progression of disease. As such, this approach could be used if there was ever an attempt to undertake a randomized controlled trial between ablation and resection for CLM.

The most common indications for image-guided ablation are:

• 1.

  Limited number (arguably less than four) and size (arguably less than 5 cm in largest diameter) of hepatic metastases in patients that cannot undergo or refuse surgery.

• 2.

  The ideal tumor for percutaneous ablation is a solitary lesion with largest diameter up to 3 cm. There is no absolute number of tumor eligibility but most series agree that patients with more than four simultaneous liver metastases are not good candidates for image-guided percutaneous ablation.

• 3.

  A tumor size up to 5 cm may be acceptable for ablation although multiple overlapping ablation will be required to achieve complete ablation with a sufficient surrounding margin (ideally a 1-cm margin all around the tumor should be created).

Contraindications:

• 1.

  No safe access of the ablation needle to the tumor despite protective maneuvers such as hydrodissection.

• 2.

  Uncorrectable coagulopathy.

• 3.

  A relative contraindication is the inability of a patient to undergo general anesthesia.

Ablation modalities