Chemotherapy for Resectable Colorectal Liver Metastases

Study Overview
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Brief Summary
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There is a degree of uncertainty regarding the role of perioperative chemotherapy (CTx) in the treatment of resectable colorectal liver metastases (CRLM). In the clinical practice, the combination of surgery and CTx is increasingly accepted as treatment for CRLM, especially in the context of patients with synchronous disease or metachronous disease with a high risk of recurrence. However, controversy exists whether all patients with resectable CRLM benefit from perioperative CTx. There is paucity of good quality studies on this topic. A pooled analysis of two phase III randomized clinical trial, closed prematurely because of slow accrual, showed a marginal statistical significance in favor of adjuvant CTx. Nevertheless, long term results of the EPOC trial founded benefit in disease free survival (DFS) with no difference in overall survival (OS) when perioperative CTx with FOLFOX4 was compared with surgery alone for resectable CRLM. Furthermore, a retrospective series from Ayez et al showed that patients with a high CRS benefit from neo-adjuvant CTx while in patients with a low risk profile did not. On the other side, another retrospective series from the MSKCC showed the timing of additional CTx for resectable CRLM was not associated with improved outcomes. The ongoing CHARISMA trial is currently comparing the outcomes of neo-adjuvant CTx followed by surgery versus surgery alone in high-risk patients with resectable CRLM. This uncertainty regarding CRLM management may partly be due to the fact that these studies are not well powered to detect minor differences in long term outcomes and they often involved a very heterogenous group of patients with both synchronous and metachronous CRLM, not stratified by clinical risk score (CRS) as described by Fong et al.

Official Title
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Perioperative Chemotherapy Versus Surgery for Resectable Colorectal Liver Metastases: a Multicenter Propensity Score Matched Analysis on Long-term Outcomes

Conditions
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Metastatic Colorectal Cancer, Metastatic Liver Cancer

Intervention / Treatment
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* Other: Liver resection and Neoadjuvant chemotherapy
* Other: Liver resection and Adjuvant chemotherapy
* Other: Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy
* Procedure: Liver resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years with resectable liver metastases of histologically confirmed primary colorectal carcinoma. Minimum follow-up of five years. Exclusion Criteria: Patients with extrahepatic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver resection and Neoadjuvant chemotherapy<br>Liver resection and Neoadjuvant chemotherapy | Other: Liver resection and Neoadjuvant chemotherapy<br> <br> |
| Liver resection and Adjuvant chemotherapy<br>Liver resection and Adjuvant chemotherapy | Other: Liver resection and Adjuvant chemotherapy<br> <br> |
| Liver resection, Neoadjuvant and Adjuvant chemotherapy<br>Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy | Other: Liver resection, Neoadjuvant chemotherapy and Adjuvant chemotherapy<br> <br> |
| Liver resection<br>Liver resection | Procedure: Liver resection<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival based on perioperative treatment | Overall survival based on perioperative treatment | 5 years of follow-up | 
| Cancer survival based on perioperative treatment | Cancer survival based on perioperative treatment | 5 years of follow-up | 
| Disease-free survival based on perioperative treatment | Disease-free survival based on perioperative treatment | 5 years of follow-up | 
| Peri-operative morbidity | Peri-operative morbidity | 5 years of follow-up | 
| Peri-operative mortality | Peri-operative mortality | 5 years of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, cancer survival and disease-free survival related with biological markers | Overall survival, cancer survival and disease-free survival related with biological markers | 5 years of follow-up | 
| Overall survival, cancer survival and disease-free survival related with hidden no resected liver lesions. | Overall survival, cancer survival and disease-free survival related with hidden no resected liver lesions. | 5 years of follow-up | 
| Overall survival, cancer survival and disease-free survival based related with simultaneous thermal ablation performed at the same time of the surgical excision. | Overall survival, cancer survival and disease-free survival based related with simultaneous thermal ablation performed at the same time of the surgical excision. | 5 years of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal liver metastases, Liver resection, Hepatectomy