Very Early-Onset Colorectal Cancer: Need for a Sub-Category Based on Differences in Tumor Biology, Metastatic and...

The incidence of early-onset colorectal cancer (eoCRC)-diagnosed before age 50-has been increasing annually. Notably, there is significant heterogeneity in the biology within the eoCRC group, yet the specific metastatic patterns and survival characteristics of these subgroups remain poorly understood. This study aims to investigate tumor biology, metastatic patterns, and cancer-specific survival among very-early onset CRC (VeoCRC) (20-34), eoCRC (35-49), and late-onset CRC (LoCRC) (≥ 50).

We utilized the Surveillance, Epidemiology, and End Results (SEER) database (2000-2018). Patients aged 20 and older diagnosed with primary CRC were included. The primary outcome was cancer-specific survival, assessed using Kaplan-Meier survival curves and multivariable Cox proportional hazard regression.

Of the 537,494 patients included in the study, 6307 (1.2%) were classified as VeoCRC, 50,179 (9.3%) as eoCRC, and 481,008 (89.5%) as LoCRC patients. The VeoCRC cohort had significantly higher rates of mucinous (10.3%) and signet-ring type adenocarcinomas (4.5%) than the eoCRC and LoCRC cohorts (P < .05). Early age of onset of CRC was associated with higher rates of positive lymph nodal status at the time of diagnosis (VeoCRC 43.4% vs. eoCRC 38.5% vs. LoCRC 28.2%) (P < .05). While the VeoCRC and eoCRC had similar 1-year survival, the VeoCRC cohort had a similar 5-year survival to that of LoCRC patients. On the multivariable Cox regression model, VeoCRC (HR = 1.049, [95% CI, 1.001-1.098]) and LoCRC (HR = 1.360 [95% CI, 1.337-1.383]) were associated with significantly lower survival compared to eoCRC.

VeoCRC patients have a distinct tumor biology as noted by their higher rates of signet ring cell cancers, mucinous cancers, worse tumor grades, nodal involvement and distant metastases compared to eoCRC patients. This is associated with worse 5-year cancer-specific survival compared to eoCRC, and is more consistent with the LoCRC cohort.