The Role of Systemic Therapy in Resectable Colorectal Liver Metastases: Systematic Review and Network Meta-Analysis

Abstract

Background Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. Methods We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). Results Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. Conclusions This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

Postoperative adjuvant chemotherapy is important for improving long‐term survival in patients with colorectal cancer liver metastases undergoing simultaneous resection

“…Approximately 30%-60% of patients with primary CRC have liver metastases, highlighting that the liver is a major organ of metastasis from CRC. 22 Surgical resection is currently the best treatment strategy for patients with resectable CRLM, as it is linked to increased long-term survival. 14,23 Several studies demonstrated that patients at high risk of recurrence of CRLM can benefit from neoadjuvant chemotherapy and POAC.…”

“…14 A systematic review and network meta-analysis concerning the role of systemic treatment for patients with CRLM only recorded improvements in PFS. 22 Therefore, the correlative studies indicate that the benefits of adjuvant treatment on prognosis in patients with CRLM remain controversial. The present results were inconsistent with the aforementioned findings as the OS rate, but not the PFS rate, was improved by POAC in patients with CRLM, and its mechanism of this effect is uncertain.…”

“…The ESMO guidelines also indicated there was insufficient evidence supporting the use of adjuvant chemotherapy in patients with CRLM who underwent upfront surgery 14 . A systematic review and network meta‐analysis concerning the role of systemic treatment for patients with CRLM only recorded improvements in PFS 22 . Therefore, the correlative studies indicate that the benefits of adjuvant treatment on prognosis in patients with CRLM remain controversial.…”

Stage IV Rectal Cancer and Timing of Surgical Approach

“…The NCCN guidelines recommend a total of 6 months of perioperative therapy with an active systemic chemotherapy regimen for patients who have undergone resection of hepatic metastases from CRC, unless they received prior oxaliplatin-based chemotherapy. 82 If chemotherapy is chosen, it is recommended to a total preoperative plus postoperative duration of 6 months, as was done in the EORTC 40983 trial. 78 Overall, among patients with resectable CRLM there is no proven survival benefit to adjuvant or perioperative systemic chemotherapy and although often recommended the benefit is likely very small if present at all.…”

Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer

“…Subgroup analysis suggested that perioperative FOLFOX seemed to benefit, in particular, patients with elevated CEA, that could mean high tumor burden and high tumor activity [ 159 ]. Meta-analyses also showed a benefit of perioperative chemotherapy in PFS and disease-free survival (DFS) but not in OS in patients with resectable CRLMs [ 160 , 161 , 162 ].…”