Stage IV colorectal cancer with metastases confined to the liver no longer carries as dire a prognosis as it once did for a sizeable proportion of patients. With modern chemotherapy and specialized liver surgery, 10-year survival has improved dramatically over the past decade, according to presentations at the 35th ESMO Congress, held October 8-12 in Milan, Italy. Recent studies show 5‑year survival rates of almost 40% and 10-year survival rates of 24%.

"Ten years ago the criteria for liver resection were much more restrictive than they are today. Less than 10% of patients with liver disease were considered eligible for surgery, and only 1 in 3 were cured. Ten-year survival was 3% a decade ago; now it is 24% for stage IV disease and liver metastases only," said Graeme Poston, MD, liver surgeon at University Hospital Aintree, NHS Trust, Liverpool, UK, and winner of the prestigious Stanford Cade Medal in 2010 for his work in liver cancer. "The chance of curing a patient is small, but we can reset that clock by resecting liver metastases," he told listeners at the ESMO/ESTRO/ESSO Joint Symposium on multidisciplinary management of colorectal cancer.¹

Current criteria for liver surgery include disease confined to the liver, resectable with adequate margins ("according to the surgeon, not the textbook," said Dr. Poston), adequate future liver remnant of 25% to 30%, and preservation of liver anatomy. About 20% of patients with liver metastases are now resectable, and chemotherapy brings another 10% to 30% to resection.

Dr. Poston emphasized the need for multidisciplinary management and specialized services for this patient group. "Patients need to be evaluated and treated by a liver surgeon. Currently too many patients are being managed by a general surgeon. The surgeon's experience is important,"  he said. Regarding multidisciplinary management, he commented, "We cannot work in isolation."

He was optimistic about this being a potentially curative disease. "In the year 2020, we might have 50% 5-year overall survival," he told listeners.

Much of Dr. Poston's presentation was based on data from the LiverMetSurvey (www.livermetsurvey.org), a European registry developed at six specialized cancer centers in Europe including 11,887 patients. These data show that resection benefits subgroups not traditionally thought to be candidates: patients with metachronous metastases, up to 10 metastatic sites in the liver, or larger tumors. "At 10 years, we have good results. If you can remove it, do it," he recommended.

Related Meta-analysis

A separate poster presentation of a meta-analysis based on 116 studies of patients with colorectal cancer and resected liver metastases showed a 5-year overall survival rate of 39%, an increase of 5% to 9% from 2001, said lead author Aliki Taylor, MD, Epidemiology Department, Amgen Ltd, Uxbridge, UK.² Dr. Poston was senior author of this poster.

"We wanted to tease out which groups had the best survival, and we found that those with solitary liver metastases had a 5-year overall survival rate of up to 70%," Dr. Taylor said.

Overall survival ranged from 16% to 71% in the studies included in the meta-analysis Patients with extrahepatic metastases had a median survival of 2.5 years, whereas those with metastases confined to the liver had a median survival of 3.6 years.

Postoperative mortality was low, ranging from 0% to 4%, which is an important point, she said. The most frequent morbidity was wound infection, reported in 4.8% of cases.

Prognostic factors correlated with shorter survival included more than one liver metastasis, node-positive primary tumor, positive resection margins, extrahepatic disease, poor differentiation of primary tumor, tumor size greater than 5 cm in diameter, and carcinoembryonic antigen (CEA) level.

Dr. Taylor said that these factors might be useful in determining optimal treatment for patients with colorectal cancer and liver metastases.

Need for Multidisciplinary Approach

Fortunato Ciardiello, MD, a member of ESMO's Steering Committee and Professor of Medical Oncology at the Second University of Naples, Italy, fully agreed with Dr. Poston's statement about the need for a multidisciplinary approach. "Patients with metastatic disease should see a colorectal surgeon, a liver surgeon, and a medical oncologist to define optimal therapy."

This is even more important for liver metastases that are initially unresectable due to the number of metastases or location. "A complex approach is needed to decide the optimal time for surgery, and a very skilled liver surgeon is needed to define anatomy."

Medical oncologists should use the most active therapy for the shortest time, he said, to achieve tumor shrinkage without harming the normal liver.

"European surgeons have pursued this approach most aggressively. The paradigm has changed the way we consider liver disease. Up to 30% of patients with stage IV colorectal cancer and liver-only metastasis can undergo successful resection. Some of them can have a resection upfront, and many of those with unresectable disease can be converted to resection," Dr. Ciardiello commented.

References

1. Poston GJ: It's resectable, but is it curable? ESMO/ESTRO/ESSO Joint Symposium. Surgery, radiotherapy and ablation of metastatic disease and chemotherapy for localized disease: Changing roles in multidisciplinary management of colorectal cancer. 35th ESMO Congress. Abstract 59IN. Presented October 9, 2010.

2. Taylor A, Kanas G, Langeberg WJ, et al: Survival after surgical resection of hepatic metastases from colorectal cancer: A systematic review and meta-analysis. 35th ESMO Congress. Abstract 632P.  Presented October 10, 2010.