Young patients with metastatic colorectal cancer at higher risk

Colorectal cancer in patients younger than 40 is more likely to grow despite treatment and young patients are at greater risk of death than people in other age groups. Christopher Lieu, MD, CU Cancer Center investigator

That’s according to research presented to the 2013 European Cancer Congress in Amsterdam. The team of scientists is led by an investigator at University of Colorado Cancer Center.

An analysis of 20,034 patients in 24 phase III clinical trials showed that the youngest and oldest patients had the highest risk of disease progression and death, compared to middle-aged patients. When compared to 57 year-olds, people under 40 had a 30% increased risk of dying from the disease, and, when compared to 61-year-olds, they had a 28% increased risk of their disease spreading during the first year of follow-up.

Colorectal cancer occurs in 4.6% of patients who are younger than 50, the incidence of the disease has been increasing at a rate of 1.5% per year from 1992 to 2005 in this age group. The most dramatic increases have been observed in the 20-29 year-old group, with an annual 5.2% increase in cases in men and a 5.6% increase in women. In the 30-39 year-old group, there has been an annual 3% increase in men and a 2% increase in women.

“The reasons why the incidence of colorectal cancer is increasing in younger patients remain unknown, although genetic predisposition, environmental factors, fewer early cancer detections in this population or a combination of these factors are thought to play a role,” said Christopher Lieu, MD, a CU Cancer Center investigator and assistant professor at CU’s School of Medicine.

“We carried out this study to see whether age was associated with time until cancer progresses or the patient dies. We also wanted to get a better picture of the ageresponse relationship and identify how risk changes as people age, rather than simply comparing one group (patients younger than 40) with another group (patients older than 40),” Lieu said.

Previous studies in this field have split the population into two mutually exclusive groups, establishing rigid limits between those patients younger than 40 or 50 and those older than that age. The new research, however, did not use such a cut-off approach and includes data spanning all ages.

“The reason we did this is we believe a 49-year-old patient with colorectal cancer may be different than a 20-year-old. By including them in the same group of people younger than 50 years old, we might be mistakenly considering them the same,” said Lieu.

Lieu and his colleagues analyzed information from a database of clinical trials in advanced colorectal cancer supported by the French “Aide et Recherche en Cancérologie Digestive” Foundation (ARCAD), which includes the 20,034 patients from 24 phase III clinical trials who were on their first treatment for the disease. There was additional patient data in which patients might be on second or third line treatment, having not responded to their initial therapy. Out of these patients, 20,011 were evaluable for analysis of survival time and time until the disease progressed.

“Analysis of this incredibly large population of patients has allowed us to answer meaningful questions, such as the outcomes of young versus older patients. Our results show young age is associated with worse overall survival and progression-free survival,” said Lieu. “Young patients with metastatic colorectal cancer represent a group who are at high risk for treatment failure.”

Despite the comprehensive nature of the study, more research will be required to identify why colorectal cancer in younger people appears to be more aggressive. Lieu and collaborators from University of Texas MD Anderson Cancer Center are now looking at the biological differences that may account for the higher risk of death in people under the age of 40.