Trends in epidemiology, clinicopathological characteristics and survival outcomes among patients with synchronous early-onset colorectal liver metastases in the United States from 2010 to 2019.

Background: Early-onset colorectal cancer (EO-CRC), defined as being diagnosed before the age of 50 years, is becoming increasingly prevalent. Among these patients, synchronous early-onset colorectal liver metastases (EO-CRLM) have emerged as a leading cause of mortality. This study aims to investigate the epidemiology, clinicopathological characteristics, and survival outcomes related to synchronous EO-CRLM to provide a clearer understanding of the challenges faced by patients with synchronous EO-CRLM.

Methods: The National Cancer Database was queried for patients with synchronous CRLM diagnosed from 2010 to 2019. Patients were then stratified by age of onset: EO-CRLM (younger than 50 years old) and late-onset colorectal liver metastases (LO-CRLM) (50 years old or older). The incidence, limited-duration prevalence rates (over a 10-year period), clinicopathological characteristics and overall survival (OS) were assessed.

Results: Among 115,422 patients with CRLM, EO-CRLM and LO-CRLM were observed in 17,536 (15.2%) patients and in 97,886 (84.8%) patients, respectively. The annual age-adjusted incidence of EO-CRLM increased from 0.48 to 0.69 per 100,000 population from 2010 to 2019 [average annual percentage change (AAPC): 5.1, 95% confidence interval (CI): 4.1 to 6.1], significantly faster than that of LO-CRLM (AAPC difference: 3.5, 95% CI: 2.5 to 4.5; P<0.001). The 10-year limited-duration prevalence for EO-CRLM increased from 0.0004% in 2010 to 0.0020% in 2019 (AAPC: 15.7, 95% CI: 10.2 to 21.5). A comparison of the clinicopathological features revealed that, compared with LO-CRLM, EO-CRLM patients were more likely to reside in urban areas, have higher rates of high school completion, have higher income, and be covered by private insurance/managed care. Genetic analysis revealed EO-CRLM with microsatellite instability (MSI)-high had the largest increase of AAPC of 28.7 (95% CI: 13.1 to 46.3) compared to MSI-low and microsatellite stability (MSS) (P<0.001). Similarly, EO-CRLM patients had a rapid rise in Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations with AAPC of 10.6 (95% CI: 8.8 to 12.5). Compared with LO-CRLM, EO-CRLM was associated with improved OS in inverse probability of treatment weighting-adjusted Cox proportional hazards regression analysis (hazard ratio: 0.876, 95% CI: 0.838 to 0.915; P<0.001).

Conclusions: The incidence of EO-CRLM has increased rapidly, and represents a distinct population in terms of socioeconomic and clinicopathological characteristics. Among this cohort, the prognosis of patients with EO-CRLM was favorable compared to that of patients with LO-CRLM.