In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.

To assess the efficacy and application value of NAC in patients with resectable CRLM.

We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.

In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).

We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.

• Colorectal neoplasm
• Neoadjuvant chemotherapy
• Systematic review
• Randomized controlled trials
• Meta-analysis
• Colorectal liver metastases

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic/administration & dosage
• Antimetabolites, Antineoplastic/therapeutic use
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemotherapy, Adjuvant/trends
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Disease-Free Survival
• Female
• Fluorouracil/administration & dosage
• Fluorouracil/therapeutic use
• France/epidemiology
• Hepatectomy/methods
• Humans
• Japan/epidemiology
• Leucovorin/administration & dosage
• Leucovorin/therapeutic use
• Liver Neoplasms/drug therapy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoadjuvant Therapy/methods
• Organoplatinum Compounds/administration & dosage
• Organoplatinum Compounds/therapeutic use
• Oxaliplatin/administration & dosage
• Oxaliplatin/therapeutic use
• Perioperative Period/trends
• Retrospective Studies
• Vitamin B Complex/administration & dosage
• Vitamin B Complex/therapeutic use

There are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the survival benefit of selective NAC administration in this patient population based on tumor characteristics.

Borderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed.

The BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397).

Defining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.

• Chemotherapy
• Colorectal cancer
• Liver metastases
• Liver resection

• chemotherapy
• colorectal liver metastases
• meta-analysis
• neoadjuvant

Systemic chemotherapy for stage IV colorectal cancer has advanced markedly in the recent years. We report an unusual case of 13 synchronous liver metastases for which a pathological complete response was achieved with neoadjuvant chemotherapy (NAC) consisting of a combination of 5-fluorouracil (5-FU), oxaliplatin, leucovorin (mFOLFOX6), and bevacizumab.

A 44-year-old man was diagnosed with colorectal cancer with synchronous liver metastases. We resected the primary rectal tumor first. Further, after providing NAC for hepatic metastases, lateral segmentectomy and partial resection of the liver were performed. The subsequent result was compatible with a complete pathological response. The postoperative course was uneventful, and the patient is currently alive 5 years after the first surgery without evidence of recurrence and without adjuvant chemotherapy.

For patients with initially resectable colorectal liver metastases, the survival benefits of NAC are still unclear. We report a rare case of 13 synchronous liver metastatic lesions from rectal cancer with a complete pathological response after neoadjuvant bevacizumab-containing chemotherapy.

• Liver metastases
• Neoadjuvant chemotherapy
• Rectal cancer

• clinical risk scores
• colorectal liver metastases
• liver resection prognosis
• neoadjuvant chemotherapy

AIM: To offer an up-to-date review of all available treatment strategies for patients with synchronous colorectal liver metastases (CLM).

METHODS: A comprehensive literature search was performed to identify articles related to the management of patients with synchronous CLM. A search of the electronic databases PubMed, MEDLINE, and Google Scholar was conducted in September 2014. The following search terms were used: synchronous colorectal liver metastases, surgery, stage IV colorectal cancer, liver-first approach, and up-front hepatectomy. These terms were employed in various combinations to maximize the search. Only articles written in English were included. Particular attention was devoted to studies and review articles that were published within the last six years (2009-2014). Additional searches of the cited references from primary articles were performed to further improve the review. The full texts of all relevant articles were accessed by two independent reviewers.

RESULTS: Poor long-term outcomes of patients with synchronous CLM managed by a traditional treatment strategy have led to questions about the timing and sequence of possible therapeutic interventions. Thus, alternative paradigms called reverse strategies have been proposed. Presently, there are four treatment strategies available: (1) primary first approach (or traditional approach) comprises resection of the primary colorectal tumor followed by chemotherapy; subsequent liver resection is performed 3-6 mo after colorectal resection (provided that CLM are still resectable); (2) simultaneous resection of the primary colorectal tumor and CLM during a single operation presents intriguing options for a highly select group of patients, which can be associated with significant postoperative morbidity; (3) liver-first (or chemotherapy-first) approach comprises preoperative chemotherapy (3-6 cycles) followed by liver resection, adjuvant chemotherapy, and resection of the primary colorectal tumor (it is best suited for patients with asymptomatic primary tumors and initially unresectable or marginally resectable CLM); and (4) up-front hepatectomy (or “true” liver-first approach) includes liver resection followed by adjuvant chemotherapy, colorectal resection, and adjuvant chemotherapy (strategy can be offered to patients with asymptomatic primary tumors and initially resectable CLM).

CONCLUSION: None of the aforementioned strategies appears inferior. It is necessary to establish individual treatment plans in multidisciplinary team meetings through careful appraisal of all strategies.

• Colorectal cancer
• Liver-first approach
• Reverse strategy
• Simultaneous resection
• Up-front hepatectomy

• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/adverse effects
• Carcinoma/mortality
• Carcinoma/secondary
• Carcinoma/therapy
• Chemotherapy, Adjuvant
• Colectomy/adverse effects
• Colectomy/mortality
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Drug Administration Schedule
• Hepatectomy/adverse effects
• Hepatectomy/mortality
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Neoadjuvant Therapy
• Neoplasm Staging
• Patient Selection
• Risk Factors
• Time Factors
• Treatment Outcome

• chemotherapy
• liver metastasis
• liver surgery
• neo-adjuvant
• synchronous

• Disappearing liver metastases (DLM)
• complete pathological response
• contrast-enhanced intraoperative ultrasound (CE-IOUS)
• liver imaging

• Chemotherapy, Adjuvant
• Colorectal Neoplasms/pathology
• Hepatectomy
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Multimodal Imaging
• Positron-Emission Tomography
• Postoperative Complications/epidemiology
• Tomography, X-Ray Computed

Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases (CLM). Objectives of surgical strategy are low intraoperative blood loss, short liver ischemic times and minor postoperative morbidity and mortality. Blood loss is an independent predictor of mortality and compromises, in common with postoperative complications, long-term outcome after hepatectomy for CLM. The type of liver resection has no impact on the outcome of patients with CLM; wedge resections are not inferior to anatomical resections in terms of tumor clearance, pattern of recurrence or survival. Despite the lack of proof of survival benefit, routine lymphadenectomy has been advocated, allowing the detection of microscopic lymph node metastases and with prognostic value. In experienced hands, minimally invasive liver surgery is safe with acceptable morbidity and mortality and oncological results comparable to open hepatic surgery, but with reduced blood loss and earlier recovery. The European Colorectal Metastases Treatment Group recommended treating up front with chemotherapy for patients with both resectable and unresectable CLM. However, neoadjuvant chemotherapy can induce damage to the remnant liver, dependent on the number of chemotherapy cycles. Therefore, in our opinion, preoperative chemotherapy should be reserved for patients whose CLM are marginally resectable or unresectable. A meta analysis of randomized trials dealing with perioperative chemotherapy for the treatment of resectable CLM demonstrated a benefit of systemic chemotherapy but did not answer the question of whether a neoadjuvant or adjuvant approach should be preferred. Analysis of the literature demonstrates that the results of specialized centers cannot be attained in the reality of comprehensive patient care. Reasons behind the commonly poorer results seen in cancer networks as compared with literature-based data are, on the one hand, geographical disparities in access to specialized surgical and medical care. On the other hand, a selection bias in the reports of the literature may be assumed. Studies of surgical resection for CLM derive almost exclusively from case series generally drawn from large academic centers where patient selection or surgical expertise is superior to what is found in many communities. Therefore, we may conclude that the comprehensive propagation of the standards outlined in this paper constitutes a major task in the near future to reduce the variations in survival of patients with CLM.

• Liver metastases
• Colorectal cancer
• Surgery
• Chemotherapy
• Outcome

• neoadjuvant therapy
• folfox
• hepatectomy
• colorectal cancer metastases
• survival