Published online Sep 27, 2022. doi: 10.4240/wjgs.v14.i9.904
Peer-review started: March 3, 2022
First decision: April 19, 2022
Revised: April 28, 2022
Accepted: August 26, 2022
Article in press: August 26, 2022
Published online: September 27, 2022
Colorectal cancer (CRC) represents an important disease burden worldwide, being the third most common malignancy and the second leading cause of cancer mortality. Many patients are de novo metastatic at presentation, and liver metastasis is common in CRC. In selected patients with colorectal liver metastases (CRLM) (i.e., the liver as the only metastatic site), surgery can be performed directly, but some patients with resectable CRLM will require neoadjuvant chemotherapy (NC) to increase the radical resection rate and treat occult metastases. On the other hand, chemotherapy can cause liver injury that will lead to impaired remnant liver function.
For resectable CRLM, oxaliplatin-based regimens have been preferred to irinotecan-based regimens as the first-line treatment because of lower occurrences of alopecia and gastrointestinal toxicity. Irinotecan has been suggested for patients with resectable CRLM, but data for such patients are limited and whether outcomes are improved remains debatable. Therefore, even though NC improves the survival outcomes for selected patients with CRLM, the benefits of irinotecan-based regimens are still under debate.
This study investigated the benefits of irinotecan- vs oxaliplatin-based NC regimens in patients with resectable CRLM.
At a single hospital in China, 554 patients received NC and underwent hepatectomy for CRLM from September 2003 to August 2020. In order to manage confounding factors, a 1:1 propensity score matching (PSM) was performed. Overall survival (OS), progression-free survival (PFS), intraoperative blood loss, operation time, and postoperative complications were compared between the two groups.
In the present study, NC regimens were based on oxaliplatin in 353 (63.7%) patients and on irinotecan in 201 (36.3%). Finally, 175 patients who received irinotecan-based NC were matched to 175 who received oxaliplatin-based NC. Hence, the two groups were balanced regarding demographic, therapeutic, and prognostic characteristics. After PSM, the 5-year PFS rates were 18.0% for irinotecan-based NC and 26.0% for oxaliplatin-based NC, while the 5-year OS rates were 49.7% for irinotecan-based NC and 46.8% for oxaliplatin-based NC. Intraoperative blood loss (201 vs 264 mL, P = 0.024), operation time (188 vs 208 min, P = 0.012), and postoperative complications (28.6% vs 42.3%, P = 0.019) all favored the irinotecan-based NC group. In the multivariable analysis, carbohydrate antigen 19-9 [hazard ratio (HR) = 1.52, 95% confidence interval (CI): 1.03-2.24], RAS mutation (HR = 1.47, 95%CI: 1.13-1.91), response to NC (HR = 1.83, 95%CI: 1.21-2.76), tumor size > 5 cm (HR = 1.48, 95%CI: 1.06-2.06), and tumor number > 1 (HR = 1.45, 95%CI: 1.08-2.15) were independently associated with the PFS.
In patients with CRLM, the PFS and OS are similar between irinotecan- and oxaliplatin-based NC. On the other hand, irinotecan-based NC is superior to oxaliplatin-based NC in terms of shorter operation time, smaller intraoperative blood loss, and fewer postoperative complications.
This retrospective cohort analysis was the first to compare the OS and PFS of irinotecan-based NC vs oxaliplatin-based NC in patients with CRLM. Even though these results can help determine the best options for patients with CRLM, multicenter randomized controlled trials would be required for confirmation. In addition, future studies could examine different dosing strategies in patients with CRLM.