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

TL;DR

A short two-cycle chemotherapy before surgery for high-risk colorectal liver cancer showed good results with minimal side effects, offering a safer and effective treatment option.

Contribution

This study demonstrates the safety and efficacy of a two-cycle neoadjuvant CAPOX plus bevacizumab regimen for high-risk colorectal liver metastases.

Findings

53.7% of patients achieved more than 50% tumor marker reduction biochemically.

TRG 3 was the most common pathologic response, observed in 57.1% of cases.

Patients with tumors <5 cm and those receiving adjuvant therapy had significantly improved survival outcomes.

Abstract

The optimal duration of chemotherapy before surgery for high-risk colorectal cancer liver metastases is a subject of ongoing debate. Prolonged treatment can lead to significant toxicity and delay potentially curative surgery. This study investigated whether a shorter, two-cycle chemotherapy regimen administered before surgery could achieve clinically relevant oncologic response with improved tolerability. Our findings from 57 patients indicate this abbreviated approach was safe and feasible, demonstrating meaningful biochemical, radiologic, and pathologic tumor responses with an acceptable toxicity profile. This suggests that a less intensive neoadjuvant strategy could be a viable option for carefully selected patients with high-risk colorectal liver metastases, potentially optimizing patient outcomes and facilitating timely surgical intervention. These insights may help guide future treatment decisions for this complex clinical scenario.

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 <5 cm (84.2%), and 47% had bilobar disease. Minor hepatectomy was performed in 65% of cases, predominantly via open surgery (72%). Grade ≥3 treatment-related adverse events occurred in 6 patients (10.6%), mainly neutropenia and diarrhea. Biochemically, 53.7% achieved >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.

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