Case Report: Cerebral metastasis following standard therapy in BRAF/KRAS wild-type colorectal cancer: an unusual presentation of disease progression.

Brain metastasis from colorectal cancer (CRC) is typically associated with advanced systemic disease and aggressive molecular features. CRC with wild-type KRAS/BRAF, microsatellite stability, and low tumor mutational burden is generally considered to have a low risk of central nervous system (CNS) dissemination. We report the case of a 66-year-old woman with sigmoid colon adenocarcinoma who initially presented with locoregionally advanced disease and distant metastasis. She received neoadjuvant chemotherapy with six cycles of mFOLFOX regimen, followed by high anterior pelvic resection with covering ileostomy and then another six cycles of adjuvant chemotherapy, achieving apparent systemic remission on serial positron emission tomography/computed tomography (PET/CT) imaging. Molecular profiling revealed a microsatellite-stable tumor with low tumor mutational burden, wild-type KRAS/NRAS/BRAF, and a TP53 mutation. The patient developed delayed multiple brain metastasis more than 1 year after completion of systemic therapy with heterogeneously enhancing intracranial lesions with surrounding vasogenic edema. She underwent neuronavigation-guided craniotomy with near-total resection of the dominant lesion, and histopathology confirmed metastatic adenocarcinoma of colorectal origin. Overall, she had an unusual pattern of disease progression in molecularly low-risk CRC, indicating that delayed CNS metastasis can occur despite apparent systemic remission. These findings challenge current assumptions regarding CNS risk stratification in CRC and raise important questions about the need for individualized neurological surveillance strategies in selected patient subgroups.