Incidence, demographics, and survival of patients with brain metastases from stage IV colorectal cancer: a population-based study from 2013 to 2023.

Introduction: Colorectal cancer (CRC) is the third most common cancer globally with rising incidence in the young population. While rare, brain metastasis (BM) in CRC patients leads to significant morbidity and mortality. The incidence of BM is expected to rise due to improved screening and treatments extending patient survival. However, limited screening guidelines exist to detect BM in patients with CRC.

Methods: Adult patients with colon and rectum tumors, with and without brain metastases, diagnosed between January 1, 2013, and December 31, 2023, were identified using ICD-10 codes from the TrinetX Oncology database. Statistical analyses were performed on TrinetX. The "incidence and prevalence" function assessed BM prevalence, while the "explore cohorts" function evaluated BM diagnoses over time. The "compare cohorts" function compared patient demographics and oncological characteristics, and the "compare outcomes" function generated Kaplan-Meier survival curves.

Results: There were 8,621 patients with CRC diagnosed at Stage IV and 279 (3.4%) developed BM. Patients who develop BM were younger (58.5 ± 12.6 years vs. 62.3 ± 14 years, p < 0.001) and a greater proportion had a KRAS mutation (37.0% vs. 16.0%, p < 0.001) and HER2 amplification (23.0% vs. 12.0%). BM were more common in primary CRC located on the left, specifically in the rectum (41.0%, vs. 36.0%, p < 0.001) or rectosigmoid junction (48.0% vs. 24.0%, p < 0.001). Patients with lung metastasis (OR [95%CI]: 1.67 [1.11-2.57]) or bone (OR [95%CI]: 4.30 [3.05-5.85]) had increased odds of developing BM. Patients with bone metastases developed BM at a median time of less than six months. Stage IV CRC patients who developed BM had decreased overall survival compared to those without BM (liver HR [95%CI]: 1.35 [1.11-1.64]; lung: 1.98 [1.62-2.43]; bone: 1.69 [1.42-2.07]).

Conclusion: Brain metastasis significantly reduces overall survival in Stage IV CRC patients. Stage IV CRC with pulmonary or osseous metastases have increased risk of BM development. These patients merit increased surveillance to identify BM early and improve survival. Other risk factors include a younger age at diagnosis, left sided primary tumor, KRAS mutation, or HER2 amplification.