Understanding Colorectal Cancer

 

 

Understanding the link between colorectal cancer and metastatic liver cancer

Prevalence
Colorectal cancer is one of the most common malignancies in industrialized nations, ranking fourth behind lung cancer, breast cancer and prostate cancers. About 140,000 new cases are diagnosed annually in the United States.

Colorectal cancer is the second most lethal malignancy after lung cancer. According to the American Cancer Society, colon and rectal cancers combined cause about 55,000 deaths in the United States each year.

The connection to metastatic liver cancer
There are important distinctions between primary and secondary liver cancers. In primary liver cancer, the cancerous cells originate in the liver. The prevalent form of primary liver cancer originates in the hepatocytes, the most common type of liver cell, and can either begin as a single tumor or in simultaneous spots in the liver. When the cancer originates from another part of the body such as the colon, and metastasizes (spreads) to the liver, the condition is known as metastatic colon cancer.

In the United States, the vast majority of patients with liver cancer developed it as a secondary condition rather than as a primary cancer originating in the liver. In up to 70% of colorectal cancer cases, the cancer eventually metastasizes to the liver. Even if the primary (colon) tumor is completely removed, metastatic liver cancer remains a risk for many patients.

Treatment options differ depending on the location of the liver tumor and whether or not it is primary or metastatic. Although surgery is a widely accepted treatment, only about 25% of patients with metastatic colorectal cancer confined to the liver are surgical candidates due to the size, distribution or accessibility of the tumors.

Prognosis    
For patients whose cancer is confined to the liver and is surgically accessible, the five-year survival rate is approximately 35%. By contrast, in patients with similar disease who are not surgical candidates and who receive systemic chemotherapy, there are very few who survive 5 years.

The American Cancer Society reports the death rate from colorectal cancer has declined for the past 15 years due to fewer incidents of primary colorectal cancer, earlier diagnoses and improved treatments. This includes promising developments in minimally invasive interventions that offer treatment options for patients with inoperable metastases confined to the liver.

Treatment options
Current treatment regimens for liver cancer include surgical excision, systemic chemotherapy, radio frequency ablation (RFA), cryotherapy, alcohol injection, laser photocoagulation, hepatic arterial chemotherapy (HAC) and trans-arterial chemo-embolization (TACE). Additional information on these and other treatments is available from the National Cancer Institute. Each of these treatment options has limitations, and none has been adopted as the standard procedure for treatment of liver cancer.

Developmental treatments include tumor vaccines, cytotoxic drugs, gene therapy and hormone receptor blocking agents. Despite decades of research, these new treatments under investigation have so far failed to make any significant impact on management of patients with liver cancer.

One promising treatment for patients with inoperable metastatic liver cancer is a procedure known as Selective Internal Radiation Therapy (SIRT). SIRT involves the introduction of yttrium-90 containing SIR-Spheres microspheres into the liver via a catheter. Treatment is administered on an outpatient basis, and side effects are generally fewer than with alternative treatments.

Because liver tumors tend to be hypervascular (their outer rims contain many capillaries), the infused SIR-Spheres microspheres become trapped in the small blood vessels supplying the tumor. This is due to the fact that liver tumors receive most, if not all, of their blood supply from the hepatic (liver) artery, and the radioactive microspheres are injected into the hepatic artery and carried by the blood flow to the tumor. Once trapped within the capillaries supplying the tumor, SIR-Spheres microspheres irradiate the cancer cells, leading to the destruction of the tumor while the normal liver tissue remains relatively unaffected.
Clinical studies
There have been many clinical trials involving SIR-Spheres microspheres. In a randomized clinical trial involving individuals with inoperable metastases in the liver, patients treated with SIR-Spheres microspheres and hepatic arterial chemotherapy (HAC) fared better than patients receiving only HAC. This pivotal study provided the basis for FDA approval of SIR-Spheres microspheres in the USA. In the study, patients treated with SIR-Spheres microspheres and HAC had a median time to disease progression, as measured by tumor size, of 15.9 months vs. 9.7 months for those receiving HAC alone. Survival rates for the patients receiving SIR-Spheres microspheres were higher at various intervals than for those just receiving HAC: 72% vs. 68% at one year; 39% vs. 29% at two years; 17% vs. 6% at three years; and 3.5% vs. 0% at five years.

In a separate randomized trial, patients receiving a combined chemotherapy treatment of fluorouracil (5-FU) and leucovorin plus SIR-Spheres microspheres showed more favorable results in response rate, time to disease progression (18.6 months vs. 3.6 months) and survival benefit (29.4 months vs. 12.8 months) than patients only receiving chemotherapy. Positive outcomes have also been realized in phase I dose-escalation studies involving SIRT plus irinotecan (median time to disease progression of 7.5 months; median survival of 12 months)5 or SIR-Spheres microspheres combined with fluorouracil, leucovorin and oxaliplatin (FOLFOX4) with median time to disease progression of 7 months and a median survival that had not yet been reached at the time of the study's publication.

A retrospective review of 116 chemo-refractory patients who received SIRT to treat colorectal cancer metastatic to the liver following failed first- and second-line chemotherapy demonstrated objective response rates at three months of 90% by PET scan. These patients had a median survival of approximately 11 months.