Metastatic Colorectal Cancer Diagnosed Before Age 35: A Distinct Subset of Early-Onset Disease?

Abstract

The incidence of early-onset colorectal cancer (CRC), commonly defined as diagnosis prior to age 50, is increasing. Studies of patients diagnosed prior to age 35 as a distinct subset of all early-onset patients have yielded inconsistent results. We extracted prospectively collected data from consecutive patients with metastatic colorectal cancer (mCRC) entered in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australasian registry. We focused on comparing demographic and clinicopathologic characteristics of those diagnosed < 35Y with remaining early-onset patients (35-49Y) whilst including a comparison to older patients (≥ 50Y) as a reference point. Molecular data were examined from 2015 when testing became reflexive. From July 2009 to December 2023, we identified 4399 patients with mCRC, including 133 (3.0%) < 35Y, and 537 (12%) 35-49Y. The proportion of < 35Y among newly diagnosed mCRC increased per calendar year (odds ratio 1.07, 95% CI 1.02-1.11). Gender, ECOG performance status and primary tumour location were similar for < 35Y and 35-49Y. Compared to 35-49Y, < 35Y had more de novo metastatic disease (79% vs. 70%; p = 0.04), BRAF V600E mutations (32% vs. 10%, p < 0.001) and deficient mismatch repair (dMMR) tumours (9.8% vs. 2.8%, p = 0.008). Rates of chemotherapy, rates of liver resection and overall survival (OS) were similar between < 35Y and 35-49Y. Multiple differences were observed between < fand 35-49Y, most notably a higher rate of BRAF V600E mutations and dMMR cancers. Collectively, these findings may inform the interpretation of clinical outcomes, refine screening approaches and advance understanding of CRC tumorigenesis in younger patients.