A new study contradicts prior research suggesting that patients with early-onset colorectal cancer (CRC) require more aggressive treatment due to distinct tumor biology.

The study, published in the Journal of the National Cancer Institute, did show differences in clinical characteristics between early-onset and average-onset CRCs.

However, there were no significant differences in tumor genomics or outcomes between early-onset and average-onset CRCs.

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The researchers analyzed data from 1446 patients — 759 with early-onset CRC (diagnosed before age 50) and 687 with average-onset CRC. The early-onset CRC group was further divided by age: 35 years or younger (n=151) and 36-49 years (n=608).

Patients in the early-onset CRC groups were less likely to be current or former smokers (P <.001), to have hypertension (P < .001), and to have diabetes (P < .001) compared with patients in the average-onset CRC group.

The following cancer-specific features were more common in the 35 years and younger group and the 36-49 age group than in the average-onset CRC group:

  • Left-sided tumors — 80.8%, 83.7%, and 63.9%, respectively (P <.001 for both comparisons)
  • Rectal cancer — 33.7%, 33.7%, and 22.6%, respectively (P =.007 and P <.001, respectively)
  • Rectal bleeding — 41.1%, 41.0%, and 25.9%, respectively (P =.001 and P <.001, respectively)
  • Abdominal pain or bloating — 37.1%, 34.0%, and 26.8%, respectively (P =.01 and P =.005, respectively).

The tumor genomic analysis, which was limited to patients with microsatellite stable (MSS) tumors (n=1356), showed that TP53 alterations were enriched in the 36-49 years group compared with the average-onset CRC group (82.1% and 73.5%, respectively).

Additionally, RTK-RAS signaling pathway alterations were less frequent in the 36-49 years group compared with the average-onset CRC group (64.6% and 71.7%, respectively).

However, when the researchers adjusted for tumor location, there were no significant differences at the gene or pathway level.

The analysis of clinical outcomes was limited to patients with MSS tumors who had metastatic disease (n=1139). Results showed no significant differences between the age groups with regard to treatment response or survival.

Radiographic response to first-line chemotherapy was 71.9% in the 35 years and younger group, 61.8% in the 36-49 years group, and 66.5% in the average-onset CRC group (P =.36 and P =.70, respectively).

The median overall survival was 46.9 months, 56.4 months, and 54.5 months, respectively (P =.90 and P =.17, respectively)

“Our results demonstrate that clinical outcomes and response to chemotherapy are the same and that aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Cercek A, Chatila WK, Yaeger R, et al. A comprehensive comparison of early-onset and average-onset colorectal cancers. J Natl Cancer Inst. Published online August 18, 2021. doi:10.1093/jnci/djab124

This article originally appeared on Cancer Therapy Advisor