The incidence of early-onset metastatic colorectal cancer is rising, largely driven by increases in multiple metastases, while survival gains for patients with peritoneal involvement remain limited, according to a recent study.

Little is known about changes in patterns of metastatic disease at diagnosis, which is why a team of French researchers has examined trends in the incidence and survival of metastatic colorectal adenocarcinoma.

Published in the journal JAMA Network Open, they considered the number and location of metastases, comparing patients diagnosed before 50 years of age with older adults.

The population-based cohort study used data from the French Network of Cancer Registries and included 37,297 patients diagnosed with invasive colorectal adenocarcinoma between 2004 and 2021.

Of these, 1,558 were under 50 years of age and 9,995 presented with metastatic disease at diagnosis. Metastatic status was categorised by the number of sites and by peritoneal, lung or liver involvement. The study assessed incidence trends and one- and three-year net survival.

Colorectal cancer and peritoneal metastases

The increase in early-onset metastatic colorectal adenocarcinoma was not uniform across different metastatic patterns. The incidence of single-site metastases was stable across age groups, whereas the incidence of metastatic disease in multiple sites increased annually by 9.5% in males and 10.3% in females among patients aged 15–39 years. This rise was mainly driven by peritoneal involvement, and to a lesser extent, by liver metastases.

By contrast, no meaningful increase was observed among patients aged 50 years or older.

The probability of presenting with peritoneal metastases also increased markedly over time. Among males aged 15–39 years, the likelihood of peritoneal involvement at diagnosis was more than six times higher in 2021 than in 2004. Similar trends were observed in younger females and in patients aged 40–49 years.

Survival outcomes for peritoneal disease

Overall survival in colorectal adenocarcinoma improved during the study period, particularly among younger patients. Three-year net survival for patients aged 15–49 years with multiple-site metastatic disease increased from 9.6% in 2004 to 27.3% in 2021, while survival for those with liver metastases almost doubled from 23.2% to 40.9%.

Patient outcomes with peritoneal metastases showed only slight improvement. The three-year net survival rate for younger patients with peritoneal involvement rose from 25.7% to 28.6% during the study period, suggesting that advances in treatment have not yielded the same benefits observed in other metastatic sites.

Several study limitations were identified by the authors, including the retrospective observational design, limited geographical coverage and missing data on tumour molecular profiles and diagnostic delays. Additionally, the study lacked sufficient statistical power to evaluate tumour sub-locations and rarer metastatic sites.

However, the findings highlight the importance of increasing awareness of colorectal cancer symptoms among younger adults and ensuring prompt diagnostic evaluation. The authors also pointed out that young patients with peritoneal metastases constitute a high-risk subgroup that could benefit from more intensive management and referral to specialised centres.

They also call for further research into the lifestyle, environmental and molecular factors that may underpin the rising incidence of aggressive metastatic disease in younger generations.

Reference
Jooste V et al. Early-onset metastatic colorectal adenocarcinoma incidence and survival among patients younger than 50 years. JAMA Netw Open 2026;9(4):e268647.