Investigating survival outcomes in patients with early- vs late-onset colorectal cancer with liver metastases.
Authors: Judy Li, Giacomo Colver Waller, Yunyun Qin, Allen Yu, Thomas M Li, Deborah M Li, Rami Srouji, Camilo Correa, Spiros P Hiotis, Ganesh Gunasekaran, James O Park, Noah A Cohen
Journal: Journal of Clinical Oncology (2025)

282 Background: Approximately 50% of patients with colorectal cancer develop liver metastases (CRLM). The incidence of early onset colorectal cancer (EOCRC), defined as &lt;50 years of age at time of diagnosis, is increasing. In this study, we aim to explore the prognosis of early vs late onset colorectal cancer patients with CRLM who receive curative-intent treatment. Methods: A retrospective study was conducted to assess clinical outcomes in patients with CRLM presenting with EOCRC compared to those with late onset colorectal cancer (LOCRC). All patients underwent surgical resection and/or ablation between 2009 and 2024 at a tertiary care center. Groups were defined by patient age at the time of diagnosis of the primary tumor &lt; 50 years versus ≥ 50 years. Demographics, tumor characteristics, and treatment modalities were compared between groups using Chi-square, independent samples t-test, and median test. Survival outcomes were assessed using Kaplan-Meier. Results: 342 patients met inclusion criteria. There were 85 (24.9%) EOCRC patients, with a median age at diagnosis of 44 years versus 63 years in the LOCRC group. EOCRC patients had fewer major medical comorbidities. EOCRC patients had a smaller proportion of right-sided (15.9% vs 29.6%, P=0.049) tumors. Rates of synchronous metastases (74.1% in EOCRC vs 72.4%, P=0.781), median size (28cm in EOCRC vs 25cm, P=0.421) median number of metastases (2 in EOCRC vs 2, P=0.385), and initial CEA levels (339.18 + 1276.48 ng/ml vs 328.87 + 2520.59 ng/ml, P=0.482) were similar between groups. However, EOCRC patients had higher rates of node-positive disease (75.6% vs 58.8%, P=0.010) and Fong Clinical Risk Scores 3-5 (57.0% vs 39.7%, P=0.009). Both groups underwent similar operative management with no differences in morbidity, but more EOCRC patients received neoadjuvant therapy (82.4% vs 66.1%, P=0.017). There were no significant differences in RAS/RAF (37.6% in EOCRC vs 34.2%, P=0.669) or TP53 (25.9% vs 34.6%, P=0.98) mutational status or microsatellite instability (stable in 74.1% in EOCRC vs 69.3%, P=0.523). Both intra- (46.5% in EOCRC vs 50.6%, P=0.535) and extra-hepatic (47.7% in EOCRC vs 38.1%, P=0.129) recurrences occurred at similar rates, with no significant differences in post-recurrence treatments received. Patients with CRLM and EOCRC had significantly worse overall survival, with a median time of 80 months versus 116 months (P=0.042). Conclusions: Despite similar clinical, pathologic, and genetic features, fewer medical comorbidities, and receiving similar medical and surgical treatments, EOCRC patients had worse median overall survival than LOCRC patients. High risk Fong Clinical Risk Scores were more common in the EOCRC group, who also received neoadjuvant therapy at higher rates. Additional research is needed to understand the differences in survival.