The prognostic role of neutrophil-to-lymphocyte ratio and C-reactive protein in metastatic colorectal cancer using regorafenib: a systematic review and meta-analysis

BACKGROUND: The application of regorafenib has changed the landscape of subsequent-line treatment in metastatic colorectal cancer (mCRC). Baseline neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP), as two of the most common inflammatory factors, are suggested to be potential prognostic factors for mCRC patients treated with regorafenib, but the results are conflicting. In this study, we conducted a meta-analysis to evaluate the prognostic role of NLR and CRP in mCRC patients treated with regorafenib. METHODS: We searched online databases such as Embase, PubMed, and the Cochrane library up to April 2022, without language limitation, to identify clinical studies evaluating the prognostic role of NLR or CRP in regorafenib treated mCRC patients. The main endpoints were hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS). The associations between NLR, CRP, and the above endpoints were extracted. Review Manager 5.4 was used to conduct the combined analysis. The Newcastle-Ottawa Scale (NOS) was applied for assessing the quality of included studies. Heterogeneity was detected by chi-square-based Q test and I(2) statistic, and publication bias was evaluated by funnel plot asymmetry and Egger’s test. RESULTS: Eight studies involving 1,287 cases were included, with 5 reporting survival outcomes based on NLR level and 4 reporting survival according to CRP level. The results of meta-analysis showed that the calculated HR of OS for subsequent-line regorafenib in mCRC patients with high versus low NLR was 2.52 [I(2)=52%, 95% confidence interval (CI): 1.75–3.64; P<0.00001]. The combined HR of PFS with high versus low baseline NLR was 2.11 (I(2)=12%, 95% CI: 1.80–2.48; P<0.00001). For patients with a high level of CRP, the OS was significantly shorter when compared with patients with a low level of CRP (I(2)=0%, HR =1.88; 95% CI: 1.55–2.29; P<0.00001). CONCLUSIONS: High level of NLR could be associated with OS in mCRC patients treated with regorafenib. It is suggested that the impact of regorafenib on OS may vary according to the baseline NLR.