Survival the Same for Younger and Older Patients With Metastatic CRC

Pam Harrison

November 19, 2021

Even though younger patients with metastatic colorectal cancer (CRC) tend to be fitter and receive more intensive treatment than older patients, overall survival (OS) and progression-free survival (PFS) are remarkably similar between the two groups, according to a large phase 3 randomized trial.

"Colorectal cancer is on track to be the leading cause of cancer death in patients 20 to 49 by the year 2040, so it is important to understand survival in this population," lead author Marla Lipsyc-Sharf, MD, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Center, Boston, Massachusetts, told Medscape Medical News in an email. "The most important point for oncologists to take away from our study is that the survival of young-onset colorectal cancer does not seem to be different from that in older patients."

Previous studies comparing survival in younger versus older patients with metastatic CRC have yielded conflicting results. Lipsyc-Sharf and colleagues set out to clarify the literature in their large randomized study, published online on October 21 in the Journal of the National Cancer Institute.

For the analysis, Lipsyc-Sharf and colleagues enrolled 2326 eligible patients in the Cancer and Leukemia Group B (CALGB)/SWOG 80405 (Alliance) trial to evaluate the efficacy of chemotherapy plus a biologic to treat metastatic CRC. Slightly over 22% of participants (514 patients) were under age 50 at study enrollment, with a median age of 44.3 vs 62.5 years in those patients older than 50 years old.

The primary outcome was OS and secondary outcomes included PFS, defined as time from study entry until disease progression or death from any cause. At a follow-up of 6 years, median OS was 27.07 months in the young CRC cohort compared with 26.12 months in the older CRC cohort.

Similarly, median PFS in both younger and older cohorts was virtually identical at 10.87 months versus 10.55 months, respectively. Patients younger than age 35 did have a shorter median OS of 21.95 months and PFS of 9.33 months compared with 26.12 months and 10.55 months, respectively, for those 50 and older, but neither difference was significant.

The similar OS between the younger and older patients with metastatic CRC is "particularly interesting," the authors note, given that younger patients should, in theory, have done better than their older peers. Younger patients tend to have better overall health (less diabetes, greater physical activity), more left-sided CRC (which is associated with a better prognosis), and receive more intensive therapy.

"It's not clear at this time why the young-onset CRC patients — despite having these more favorable characteristics — did not have improved survival compared to older patients," Lipsyc-Sharf said.  

The authors suggest that this similar survival may be because younger patients tend to be diagnosed at more advanced stages, due to differences in underlying tumor biology, or due to other unknown factors. However, "additional investigation into the tumor biology, clinical characteristics, and optimal treatment of patients with [early onset] CRC is essential," the authors conclude.

The work was supported by the National Cancer Institute of the National Institutes of Health and, in part, by Bristol Myers Squibb, Genentech, Pfizer, and Sanofi. Lipsyc-Sharf has reported no relevant financial relationships.

J Natl Cancer Inst. Published online October 21, 2021. Abstract

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