Clinicopathologic characteristics, genomic signatures, and outcomes of patients undergoing resection for early- versus late-onset colorectal liver metastasis.

[BACKGROUND] While the incidence of early-onset colorectal cancer has increased over the last decade, survival outcomes of patients with early-onset versus late-onset colorectal liver metastases have not been well defined. We sought to assess differences in clinical and molecular characteristics of patients with colorectal liver metastases relative to age at disease onset.

[METHODS] Patients with liver-only colorectal liver metastases who underwent curative-intent hepatectomy in 2000-2023 were identified in a multi-institutional database. Differences in clinicopathologic characteristics and outcomes of patients with early-onset and late-onset colorectal liver metastases were assessed. Genomic signatures were examined using data from the American Association for Cancer Research GENIE and MSK-CHORD databases.

[RESULTS] Among 2,465 patients who underwent hepatectomy for colorectal liver metastases, 484 (19.6%) patients had early-onset colorectal liver metastases, and 1,981 (80.4%) had late-onset colorectal liver metastases. Patients with early-onset colorectal liver metastases more frequently were female (46.9% vs 38.0%), had a primary colorectal cancer located in the rectum/left colon (74.8% vs 68.7%), had lymph node metastasis associated with the primary tumor (57.4% vs 48.2%), and had synchronous colorectal liver metastases (65.8% vs 58.1%) compared with patients with late-onset colorectal liver metastases (all P < .05). No differences in 5-year recurrence-free survival (24.2% vs 24.8%) and overall survival (49.4% vs 48.1%) were noted after hepatectomy for early-onset versus late-onset colorectal liver metastases (both P > .05), even after adjusting for relevant clinicopathologic characteristics (recurrence-free survival: hazard ratio 1.12, 95% confidence interval 0.92-1.37; overall survival: hazard ratio 1.03, 95% confidence interval 0.76-1.39). Using the American Association for Cancer Research GENIE and MSK-CHORD cohorts, early-onset and late-onset colorectal liver metastases samples had comparable mutation rates in key genes including KRAS, BRAF, APC, TP53, PI3K3CA, and SMAD4 (all q > 0.05) CONCLUSION: Despite the presence of more aggressive clinicopathologic features, patients with early-onset colorectal liver metastases had outcomes and genomic profiles similar to patients with late-onset colorectal liver metastases. These data highlight how age at disease onset per se should not be considered an indicator of aggressive disease and poor prognosis among patients with colorectal liver metastases.