A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers

Area of Science:

• Oncology
• Gastroenterology
• Genetics

Background:

• Rising incidence of early-onset colorectal cancer (EO-CRC) lacks clear causative factors.
• Investigating clinical and genomic distinctions between EO-CRC and average-onset colorectal cancer (AO-CRC) is crucial.

Purpose of the Study:

• To determine if early-onset colorectal cancer (EO-CRC) is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC).

Main Methods:

• Compared clinical, histopathologic, and genomic characteristics of EO-CRC patients (under 50) with AO-CRC patients (50+).
• Excluded patients with specific conditions like mismatch repair deficient tumors or hereditary syndromes.
• Utilized statistical analyses to compare tumor characteristics, gene alterations, and survival rates across age groups.

Main Results:

• EO-CRC cases were more frequently left-sided and presented with rectal bleeding and abdominal pain.
• No significant differences in histopathology or genomic alterations (TP53, RTK-RAS) were found between EO-CRC and AO-CRC in microsatellite-stable tumors.
• Chemotherapy response and survival were equivalent for advanced microsatellite-stable colorectal cancers across age groups.
• Higher prevalence of pathogenic germline variants observed in the youngest EO-CRC cohort (≤35 years).

Conclusions:

• Early-onset colorectal cancer (EO-CRC) exhibits distinct clinical presentation (left-sided tumors, specific symptoms) but is otherwise clinically and genomically similar to AO-CRC.
• Current evidence does not support aggressive treatment regimens solely based on age at diagnosis for colorectal cancer.