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Poorer Progression-Free Survival and Overall Survival Seen in Youngest and Oldest Patients With Metastatic Colorectal Cancer

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Key Points

  • Risk of death was greatest among the youngest and oldest patients, with increases in risk being greatest in the first-year of follow-up.
  • Risk of death or progression was greatest among the youngest and oldest patients, with increases in risk being greatest in the first-year of follow-up.

Lieu et al recently analyzed the effect of age on outcome in patients with metastatic colorectal cancer using the ARCAD (Aide et Recherche en Cancérologie Digestive) database. The findings, reported in the Journal of Clinical Oncology, indicate a U-shaped risk of death and death or progression characterized by greatest risk among the youngest and oldest patients.

Study Details

The study included 20,023 patients from 24 first-line randomized trials in metastatic colorectal cancer with years of accrual from 1997 through 2010. Patients had a mean age of 62 years, with 4% aged ≤ 40 years and 14% aged < 50 years; 62% of patients were male, and performance status was 0 in 53% and 1 in 43%. Mean age differed significantly by sex and performance status.

Median follow-up among surviving patients was 18 months. Overall, median progression-free survival was 8.1 months and median overall survival was 17.9 months. 

Increased Risk in Younger and Older Patients

In the analysis of overall survival, compared with patients aged approximately 57 years, who constituted the reference group with lowest risk, the youngest patients (ie, those near age 18 years) had a 19% increased risk of death and the oldest patients (ie, those near age 90 years) had a 42% increased risk (P < .001), with declining risk between these extremes.

The relationship with age remained significant after adjustment for sex and performance status (P < .001). The effect of age was most marked during the first year of follow-up (P < .001), with risk increased by 28% and 71% in the youngest and oldest patients.

In the analysis of progression-free survival, compared with patients aged approximately 61 years (lowest risk of progression or death), risk of progression or death was increased by 22% in the youngest patients and by 15% in the oldest patients (P <  .001), with the difference remaining significant after adjustment for sex and performance status (P = .002). The effect of age was most marked during the first year of follow-up (P < .001), with risk increased by 29% and 19% in the youngest and oldest patients.

After adjustment for performance status, sex, and presence of liver, lung, or peritoneal metastases, age had marginal significance for overall survival (P = .08) and significance for progression-free survival (P = .005). The effect of age did not differ according to site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutation status.

The investigators concluded, “Younger and older age are associated with poorer [overall survival] and [progression-free survival] among treated patients with [metastatic colorectal cancer]. Younger and older patients may represent higher-risk populations, and additional studies are warranted.”

Christopher H. Lieu, MD, of the University of Colorado, Aurora, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the ARCAD Clinical Trials Program. Study coauthor Richard M. Goldberg, MD, reported a consultant or advisory role with sanofi-aventis and Bayer; honoraria from sanofi-aventis, Eli Lilly, and Bothera; and research funding from sanofi-aventis and Bayer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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