Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature

Table 1 Potential advantages and disadvantages of neoadjuvant chemotherapy for colorectal liver metastases

Advantages	Disadvantages
(1) Conversion to resectability	(1) Chemotherapy-associated liver injury
(2) Facilitate parenchymal-sparing or minimally invasive approach	(2) Local progression that precludes hepatic resection (rare)
(3) Higher rates of negative margins	(3) Disappearing liver metastases
(4) Improved patient selection for surgery	(4) Toxicity from chemotherapy
(5) Improved rates of multimodality therapy
(6) Early treatment of micro-metastases
(7) Ability to assess response to therapy

Table 2 Consensus statements and guidelines for the use of neoadjuvant chemotherapy in patients with colorectal liver metastases

Organization	Year	Recommendation
National Cancer Comprehensive Network[18]	2020	For resectable synchronous CRLM, can consider neoadjuvant therapy for 2-3 mo with FOLFOX, CAPOX, FOLFIRI, or FOLFOXIRI followed by synchronous or staged colectomy and hepatic resection. For unresectable synchronous CRLM, give systemic therapy with FOLFIRI/FOLFOX/CAPOX/FOLFOXIRI ± bevacizumab, FOLFIRI/FOLFOX/FOLFOXIRI ± panitumumab or cetuximab (wild-type KRAS/NRAS/BRAF), or pembrolizumab (dMMR/MSI-H only). Re-evaluate for conversion to resectable every 2 mo. For resectable metachronous metastases, resection and/or local therapy is preferred, though neoadjuvant chemotherapy for 2-3 mo with FOLFOX, CAPOX, capecitabine, or 5-FU/leucovorin can be given
American Society of Clinical Oncology[108]	2020	It is critical for a multidisciplinary team to evaluate the patient and determine eligibility for curative-intent treatment and best treatment sequence. The choice of chemotherapy depends on the resources available, toxicity concerns, whether the patient had prior chemotherapy, and the patient’s clinical performance status
SEOM, AEC, SEOR, SERVEI, and SEMNIM[109]	2020	Neoadjuvant chemotherapy might provide benefit in high-risk patients with resectable liver metastases. Neoadjuvant chemotherapy may initially turn unresectable liver metastases into resectable liver metastases with good long-term results
European Society of Medical Oncology[110]	2016	In patients with clearly resectable disease and favorable prognostic criteria, perioperative treatment may not be necessary and upfront resection is justified. In patients with technically resectable disease where the prognosis is unclear or probably unfavorable, perioperative complication chemotherapy (FOLFOX or CAPOX) should be administered. In situations where the criteria for prognosis and resectability are not sharply defined, perioperative therapy should be considered. Patients with synchronous onset of metastases should be allocated to this group and therapeutic pathway
Expert Group on OncoSurgery Management of Liver Metastases[111]	2015	For patients with resectable CRLM, chemotherapy should be given preoperatively unless resection of the primary tumor and liver metastases is considered easy. A total of 6 mo of chemotherapy is recommended, independent of whether it is given pre- or postoperatively. For unresectable CRLM, chemotherapy should be administered first with the aim of achieving resectability
International Hepato-Pancreato-Biliary Association[112]	2013	For resectable CRLM, perioperative chemotherapy with resection has shown progression-free benefits compared with resection alone. The use of an oxaliplatin-containing regimen is the reference treatment for this approach. For downsizing of unresectable CRLM, FOLFOX and FOLFIRI represent chemotherapy backbones of similar efficacy, though FOLFOXIRI may provide a higher likelihood of response
Americas Hepato-Pancreato-Biliary Association[112]	2013	For resectable CRLM, perioperative chemotherapy with resection has been shown to have improved PFS compared with resection alone. For patients with unresectable CRLM, oxaliplatin- or irinotecan-containing chemotherapeutic regimens represent the standard options, although the addition of bevacizumab carries the potential for a greater response and reduced risk for CALI. In tumors without KRAS mutations, anti-EGFR agents are a reasonable choice. In general, preoperative chemotherapy should not extend beyond 3 mo

NCT: Neoadjuvant chemotherapy; CRLM: Colorectal liver metastases; FOLFOX: Fluorouracil/leucovorin/oxaliplatin; CAPOX: Capecitabine, oxaliplatin; FOLFIRI: Fluorouracil/leucovorin/irinotecan; FOLFOXIRI: Fluorouracil/leucovorin/oxaliplatin/irinotecan; dMMR: Deficient mismatch repair; MSI-H: Microsatellite instability high; SEOM: Spanish Society of Medical Oncology; AEC: Spanish Association of Surgeons; SEOR: Spanish Society of Radiation Oncology; SERVEI: Spanish Society of Vascular and Interventional Radiology; SEMNIM: Spanish Society of Nuclear Medicine and Molecular Imaging; PFS: Progression-free survival; CALI: Chemotherapy-associated liver injury; 5-FU: 5-Fluorouracil.