Oncologic and Surgical Outcomes After Short-Course Neoadjuvant CAPOX Plus Bevacizumab in High-Risk Colorectal Liver Metastases

BACKGROUND: The optimal duration of neoadjuvant therapy for high-risk colorectal liver metastases (CRLM) remains debated. While prolonged chemotherapy may enhance response, it also increases toxicity and risks delaying potentially curative resection. These considerations have raised the question whether a short-course neoadjuvant strategy might achieve sufficient oncologic selection and response while minimizing treatment-related morbidity. METHODS: Patients with synchronous or metachronous CRLM who received two cycles of neoadjuvant CAPOX plus bevacizumab followed by curative-intent liver resection treated between 2014 and 2024 at Health Network Vienna, Austria, were included. Clinicopathologic characteristics, treatment tolerability, response assessments (biochemical, radiologic, and pathologic), and survival outcomes were collected and analyzed. RESULTS: A total of 57 patients were included (65% synchronous, 35% metachronous), with the rectum being the most frequent primary tumor site (45.6%). Most liver lesions were 50% tumor marker reduction. Radiologic assessment showed partial response in 31.6% and complete response in 1.7%. Pathologic evaluation revealed TRG 3 as the most common finding (57.1%), followed by TRG 2 in 22.5%. Subgroup analyses demonstrated significantly improved OS and RFS in patients receiving adjuvant therapy and in those with tumors < 5 cm. CONCLUSION: A two-cycle, short-course regimen of CAPOX plus bevacizumab proved both effective and safe in high-risk CRLM, achieving meaningful biochemical, radiologic, and pathologic responses with acceptable toxicity. This abbreviated approach allowed delivery of neoadjuvant therapy while limiting cumulative treatment-related toxicity, supporting its feasibility as a neoadjuvant strategy in selected high-risk CRLM patients.