No Difference in Survival for Younger, Older Patients With Metastatic CRC

Younger and older patients with metastatic colorectal cancer (CRC) have a similar survival rate despite greater treatment intensity and physical fitness in younger patients, according to a recently published study from the Dana-Farber Cancer Institute.¹ The study found no statistically significant difference in overall survival (OS) rate of patients younger or older than 50 years.

These results are surprising due to the anticipated differences in health conditions of younger patients. “As a group, younger patients are more physically active and have higher performance status and are better able to perform the activities of daily living than older patients. They also tend to be treated with higher doses of therapy and have less severe [adverse events],” study senior author Kimmie Ng, MD, MPH, director of the Young-Onset Colorectal Cancer Center at Dana-Farber, said in a statement.²

This study is the first to examine younger versus older patients with metastatic CRC, according to Ng. The incidence of early-onset CRC is on the rise, but the differences between younger and older patients with CRC are not well-understood.

The findings published in the Journal of the National Cancer Institute were based on analysis of data from the CALGB/SWOG 80405 trial (NCT00265850), a multicenter, randomized trial of first-line chemotherapy plus biologics.¹ The trial’s primary end point was OS while progression-free survival (PFS) was a secondary end point. In the trial, 514 patients were younger than 50 years old while 1812 were above 50. The median age of the younger cohort was 44.3 years while that of the older cohort was 62.5.

Based on the results of the trial, the median OS for patients under 50 was 27.07 months compared with 26.12 months for those over 50 at onset of disease (adjusted HR, 0.98; 95% CI, 0.88-1.10; P = .78). The median PFS was 10.87 versus 10.55 months, respectively (adjusted HR, 1.02; 95% CI, 0.92-1.13; P = .67). Neither OS nor PFS had a statistically significant difference between the groups, indicating that age has no relationship with survival outcomes for patients with metastatic CRC. In patients under 35, however, there was a shorter median OS of 21.95 versus 26.12 months for older onset patients, but this result is not considered statistically significant due to the low number of patients under 35 in the study [adjusted HR, 1.08; 95% CI, 0.81-1.44; P_trend = .93).

Likewise, there is no visible difference between the cancers of the different age groups on the cellular level. “Research has yet to identify consistent molecular differences in the colorectal cancer cells of younger patients and older patients,” said Marla Lipsyc-Sharf, MD, first co-author of the Dana-Farber study, in a press release. The differences in the intestinal microbiome between patients of different age groups are currently being investigated by other studies as a possible cause for the incidence of early-onset CRC.

Earlier-onset CRC has been on the rise for decades. According to JAMA Surgery, overall CRC incidence dropped by 0.92% from 1975 to 2010, while incidence for CRC in 20 to 49-year-olds rose by 1.99%.³ No overall cause for this rise is known, but it is expected to be a major area of concern in the future.

“If current trends hold, CRC is projected to be the second leading cancer and leading cause of cancer death in patients ages 20 to 49 by the year 2040,” said Lipsyc-Sharf. “It is important to understand survival in this population in order to develop tailored treatments.”

_References:

_{1. Lipsyc-Sharf M, Zhang S, Ou F, et al. Survival in young-onset metastatic colorectal cancer: findings from Cancer and Leukemia Group B (Alliance)/SWOG 80405, J Natl Cancer Inst. 2021;djab200. doi:10.1093/jnci/djab200}

_{2. Survival similar for younger and older patients with metastatic colorectal cancer, study finds. Dana-Farber Cancer Institute. Published October 27, 2021. Accessed November 1, 2021. https://bit.ly/3EDTHK3}

_{3. Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg. 2015;150(1):17-22. doi:10.1001/jamasurg.2014.1756}