Targeted follow-up and treatment strategies advised for colorectal liver metastases, study finds

A decline in the incidence of colorectal liver metastases contrasts with survival gains, which are restricted to synchronous and early metachronous disease, according to a recent study, suggesting that targeted follow-up and treatment strategies for colorectal cancer patients based on the timing of metastasis may be required.

The cohort study, led by teams at Aarhus University Hospital and Aarhus University, examined temporal patterns in incidence, characteristics and survival for colorectal liver metastases across Denmark between 2007 and 2024.

Drawing on several linked national health registries, the researchers conducted a nested medical record review to validate registry data and establish how the burden of colorectal liver metastases has evolved over time and whether survival differs by the timing of metastasis.

Synchronous colorectal liver metastases are those diagnosed at the same time as the primary tumour, while metachronous colorectal liver metastases are classified as early when occurring within 12 months of the colorectal cancer diagnosis and late when arising more than 12 months afterwards.

Between 2007 and 2021, 72,722 patients with colorectal cancer were identified, of whom 14,785 developed colorectal liver metastases. The cohort had a median age of 68.9 years, and 58.3% were male.

Identifying colorectal liver metastases

Synchronous metastases were most common (10,188 patients; 68.9%), followed by late metachronous (3,016 patients; 20.4%) and early metachronous disease (1,581 patients; 10.7%).

A detailed medical record review of 954 randomly selected patients confirmed colorectal liver metastases in 26.2% and revealed good registry accuracy, with a sensitivity of 77.2% and specificity of 94.4%.

Across all colorectal cancer cases, the five-year cumulative incidence of colorectal liver metastases was 19.8%. Incidence decreased steadily over time – from 23.1% among patients diagnosed between 2007 and 2010 to 15.3% between 2019 and 2021. The highest incidence was observed in adults under 50 years (27.2% at five-year follow-up) and in men (21.5% at five-year follow-up). Left-sided and rectal tumours carried a higher metastatic risk than right-sided disease.

The authors suggested that national colorectal cancer screening and faster diagnostic pathways may have contributed to earlier cancer detection, likely reducing metastatic progression.

Marked survival gains

Survival improved substantially for synchronous colorectal liver metastases. One-year survival rose from 47.2% between 2007 and 2010 to 58.3% between 2020 and 2024, while five-year survival increased from 13.0% to 20.7% over the same periods. Early metachronous colorectal liver metastases also showed relatively favourable outcomes, but survival for late metachronous disease remained largely unchanged, with five-year survival approximately 25–28% across all periods.

Treatment patterns were broadly stable, although the use of ablation increased markedly, from 3.8% in 2007 to 21.2% in 2021. Surgery was more common in metachronous cases, whereas most patients with synchronous colorectal liver metastases received chemotherapy.

The findings highlighted important differences between synchronous, early metachronous and late metachronous metastases, which may reflect variations in tumour biology, comorbidity burden and treatment eligibility, the authors said, although they acknowledged some study limitations.

Incomplete registry reporting likely led to an underestimation of the incidence of metastasis, particularly among frail or rapidly declining patients. Follow-up was limited in the most recent diagnostic years, and residual confounding – particularly regarding comorbidity, frailty and treatment intent – could not be ruled out. Furthermore, because it was an observational study, the design precluded causal inference, the authors added.

More personalised follow-up and therapy strategies adapted to the timing of metastatic presentation were advocated, alongside ongoing improvements in registry completeness to support accurate national surveillance.

Reference
Johannsen IR et al. Liver Metastases and Survival Among Patients With Colorectal Cancer. JAMA Netw Open 2025;8(12):e2550467.