Incidence Declines, Survival Improves for Synchronous CRLM

Colorectal liver metastases (CRLM) remain a leading cause of mortality in colorectal cancer (CRC), but new data from Denmark suggest progress is uneven.¹

Researchers found that while the cumulative incidence of CRLM declined across age groups, meaningful survival gains were largely confined to patients with synchronous disease, underscoring the need for timing-specific follow-up and treatment strategies.

This population-based cohort study is published in JAMA Network Open.

“In this nationwide study, we observed increased survival among patients with CRLM diagnosed within the first year of CRC diagnosis (ie, synchronous and early metachronous) and a decreasing cumulative incidence over time for all CRLM types,” wrote the researchers of the study. “The declining cumulative incidence of CRLM may partly be attributed to a more structured and expedited approach to cancer treatment initiation in Denmark, better organization of multidisciplinary team conferences, and the introduction of a national CRC screening program in 2014.”

CRLM occurs when CRC spreads to the liver, a common site of metastasis.² About 20% of patients have CRLM at initial CRC diagnosis, and another 40%–50% may develop it after surgery. Treatments like hepatectomy, often guided by intraoperative imaging such as contrast-enhanced ultrasound, aim to remove liver tumors and improve survival outcomes.

The study used linked Danish national health registries, including the Danish Cancer Registry, National Patient Registry, and National Pathology Registry, to identify all patients diagnosed with CRLM between 2007 and 2024.¹ Patients were classified as having synchronous, early metachronous, or late metachronous CRLM based on the timing of metastasis relative to CRC diagnosis. Cumulative incidence of CRLM was calculated at 1, 3, and 5 years following CRC diagnosis, and overall survival was estimated from the date of CRLM diagnosis. Additionally, a nested medical record review of a subset of patients (n = 954) was conducted to assess concordance between registry-based incidence estimates and clinical documentation.

Among 14,785 patients with CRLM (median [IQR] age, 68.9 [62.2-77.0] years; 58.3% male), the 5-year cumulative incidence of CRLM among patients with CRC was 19.8% (95% CI, 19.5%–20.1%). Incidence was highest in patients younger than 50 years (27.2% at 5 years; 95% CI, 25.6%–28.8%) and in male patients (21.5% at 5 years; 95% CI, 21.1%–22.0%) and declined with increasing age.

In the nested medical record review, 26.2% of patients (250 of 954) developed CRLM during follow-up. Survival improved over time for patients with synchronous CRLM, with 1-year survival increasing from 47.2% (95% CI, 45.3%–49.1%) in 2007–2010 to 58.3% (95% CI, 54.1%–62.3%) in 2020–2024, and 5-year survival rising from 13.0% (95% CI, 11.7%–14.3%) to 20.7% (95% CI, 18.1%–23.5%) across the same periods. In contrast, no corresponding improvements in survival were observed for patients with early or late metachronous CRLM.

However, the researchers acknowledged several limitations. Incomplete registration of metastatic disease may have led to underestimation of CRLM incidence, as suggested by the medical record review. Additionally, shorter follow-up for recently diagnosed patients and residual confounding by comorbidity, frailty, and treatment intent may have influenced results, and causal inferences cannot be drawn from this observational study.

Despite these limitations, the researchers highlight that the study found the cumulative incidence of CRLM declined over time and that survival improved for patients with synchronous CRLM. However, outcomes for metachronous disease remained unchanged, highlighting the need for timing-specific surveillance and treatment strategies to optimize care for all patients with CRLM.

“These findings may reflect differences in tumor biology, comorbidity burden, and treatment eligibility between metachronous and synchronous CRLM and may support targeted follow-up and treatment strategies based on the timing of metastasis,” wrote the researchers.

References

1. Johannsen IR, Boysen AK, Nielsen MF, et al. Liver metastases and survival among patients with colorectal cancer. JAMA Netw Open. 2025;8(12):e2550467. doi:10.1001/jamanetworkopen.2025.50467

2. Bonavitacola J. Ultrasound method linked with improved survival in patients with CRC liver metastases. AJMC®. October 1, 2024. Accessed January 5, 2026. https://www.ajmc.com/view/ultrasound-method-linked-with-improved-survival-in-patients-with-crc-liver-metastases