EARLY-ONSET colorectal cancer (CRC) with liver-only metastases may have distinct biological and clinical characteristics compared with disease diagnosed later in life, according to a large Australian study.
Researchers found that patients aged 50 years or younger were more likely to have left-sided tumours, synchronous liver metastases, and BRAF mutations than older patients. Younger patients also had longer overall survival and were more likely to receive active treatment, highlighting the potential importance of tailoring treatment to individual tumour biology and disease characteristics.
Researchers conducted a retrospective cohort study using prospectively collected data from the Australian Treatment of Recurrent and Advanced Colorectal Cancer registry. The analysis included 1,691 adults with CRC that had spread only to the liver, enrolled between January 2009 and September 2024.
Of these, 276 patients (16.3%) had early-onset CRC, defined as diagnosis at 50 years or younger, while 1,415 (83.7%) were aged over 50 years. The median ages of the two groups were 43 and 69 years, respectively.
Several important differences emerged between the groups. Women accounted for 48.2% of patients with early-onset CRC compared with 34.5% of the older group. Younger patients were also considerably less likely to have other health conditions: 90.1% had no recorded comorbidities compared with 59.0% of older patients.
Tumour characteristics also differed. Left-sided colon or rectal cancers were identified in 76.1% of younger patients compared with 65.7% of older patients. Additionally, 53.3% of patients with early-onset CRC had synchronous liver metastases, meaning metastatic disease was present at the time of diagnosis, compared with 42.1% of older patients.
Molecular analysis suggested further differences in the biology of early-onset disease. Among patients with available testing, BRAF mutations were identified in 13.9% of younger patients compared with 8.1% of those aged over 50 years.
However, no meaningful differences between the groups were observed for KRAS or NRAS mutations, or mismatch repair status.
Younger patients were also more likely to receive active treatment. Overall, 96.0% of patients with early-onset CRC received active treatment compared with 88.5% of older patients. Chemotherapy or biological therapy followed by surgery was used in 27.9% of younger patients, compared with 14.1% of those aged over 50 years.
Across the entire study population, 662 patients (39.1%) underwent liver resection.
Median overall survival was 3.20 years among patients with early-onset CRC compared with 2.38 years among older patients. The difference was particularly pronounced among patients whose liver metastases developed after their initial cancer diagnosis, with median survival of 8.86 years in younger patients compared with 3.83 years in the older group.
Among patients who underwent liver resection, however, survival was similar between age groups, at 5.99 years for younger patients and 5.88 years for older patients.
Genetic characteristics were also associated with outcomes. KRAS and BRAF mutations were linked to poorer survival across the study population, reinforcing the potential importance of molecular profiling when planning treatment.
The findings suggest that early and late-onset CRC with liver-only metastases may differ in tumour biology, clinical presentation, treatment patterns, and survival.
However, the authors cautioned against assuming that more aggressive treatment will benefit every younger patient. As an observational registry study, treatment was not randomly assigned, and younger patients generally had fewer comorbidities and better performance status, which may have influenced both treatment decisions and outcomes.
The researchers concluded that treatment should therefore be individualised according to factors including disease burden, comorbidities, tumour location, molecular characteristics, and the timing of liver metastases.
Reference:
Barreto S G et al. Early-Onset Colorectal Cancer With Liver-Only Metastases: A Retrospective Cohort Study Integrating Prospectively Collected Real-World Clinical and Molecular Data From an Australian National Database (2009–2024) to Guide Treatment Planning. Med J Aust. 2026.
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