Brain metastases from colorectal cancer - a retrospective dual center study

Although brain metastases (BM) represent an uncommon manifestation of colorectal cancer (CRC), their occurrence is associated with a markedly reduced life expectancy. Advances in systemic therapies and neuroimaging have led to a growing number of detected cases. However, data on prognostic markers and optimal management still remain limited. This dual center analysis from two major German cancer centers sought to describe clinical characteristics, treatment approaches and survival determinants in patients with CRC who developed BM.

All individuals diagnosed with CRC and subsequent BM between January 2000 and December 2024 were retrospectively identified from the tumor registries of the University Hospitals Wuerzburg and Frankfurt. Demographic, pathological and therapeutic parameters were extracted and analyzed. Overall survival following BM diagnosis was assessed using a multivariable Cox proportional hazards model with backward stepwise likelihood ratio selection (entry criterion p < 0.05, removal p > 0.10). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.

The study included 279 patients (Wuerzburg 48.4%, Frankfurt 51.6%). The mean age at CRC diagnosis was 62.1 years and at BM diagnosis 65.1 years; 61.6% of the patients were male. The median interval between CRC diagnosis and BM detection in metachronous patients was 40.5 months, with 11.1% exhibiting synchronous BM. Liver, lung, and bone metastases were present in 50.9%, 64.2%, and 22.6% of patients, respectively. Among tested cases, KRAS mutations were found in 54.2%. Surgical resection of BM was undertaken in 36.2%, and radiotherapy in 67.0%. On multivariable analysis, Karnfosky Performance Status emerged as independent predictors of prolonged survival (HR = 0.98; 95% CI 0.97-1-00; p = 0.008). Brain metastasis surgery showed a borderline association with improved survival (HR 0.51; 95% CI 0.26-1.00; p = 0.050). Median survival from the time of BM diagnosis was 20 months (95% CI 14.140-25.860) in the operated group compared with 3 months (95% CI 2.089-3.911) in the non-operated group.

Patients with CRC who develop BM are a subgroup with heterogeneous courses of disease. In addition to KPS, surgical resection of BM was associated with improved survival. This emphasizing the benefit of local treatment in appropriately cases. Collaborative, prospective studies are required to validate these findings and to refine therapeutic strategies for this rare entity.