Neoadjuvant chemotherapy for upfront resectable colorectal liver metastasis: Is it worthwhile?

Colorectal liver metastases (CRLM) are a crucial factor affecting survival in colorectal cancer (CRC) patients, and liver resection is the only potentially curative option for such patients. The incidence of postoperative recurrence is still high despite advances in surgical techniques. That may necessitate systemic therapy administration before resection. However, there is a significant controversy regarding the administration of neoadjuvant chemotherapy (NACT) in patients with upfront resectable CRLM. The current critical review addresses the indications, possible benefits, and limitations of NACT in patients with upfront resectable CRLM. Herein, we discuss the resectability criteria, patient evaluation methods, the importance of tumor biological/molecular profile, and the validated risk scores for recurrence after resection. NACT administration significantly improves disease-free (DFS) and progression-free survivals (PFS). In contrast, its impact on overall survival (OS) is still modest and appears to be evident only in patients with unfavorable tumor criteria. Potential disadvantages, including increased perioperative morbidity, chemotherapy-associated liver injury (CALI), and disappearing liver metastases, are also reviewed. We will also summarize evidence from published meta-analyses, prospective trials, and retrospective studies to elucidate the impact of NACT on DFS and OS. Current guideline recommendations and emerging data support a selective, risk-adapted approach rather than routine administration of NACT in all resectable cases. In conclusion, patients with unfavorable oncological features (high recurrence risk) should receive NACT before resection, while upfront surgery alone could be appropriate for low-risk patients (favorable tumor profile). It is crucial to make the management plan within a multidisciplinary framework until further consensus is achieved.