Prognostic role of the platelet to lymphocyte ratio (PLR) in the clinical outcomes of patients with advanced lung cancer receiving immunotherapy: A systematic review and meta-analysis

Abstract

Background: It remains controversial whether the platelet to lymphocyte ratio (PLR) serves as a potential indicator for the efficacy of immunotherapy in advanced lung cancer. This meta-analysis aimed to address this concern.

Methods: Up to March 2022, we searched PubMed, Embase, Web of Science and the Cochrane Library to retrieve potentially eligible articles. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the relationship between PLR and progression-free survival (PFS) as well as overall survival (OS), while the combined odds ratios (ORs) and 95% CIs were estimated to evaluate the relationship between PLR and the objective response rate (ORR) as well as the disease control rate (DCR). Subgroup analyses were further performed to detect the source of heterogeneity and potential predictive value of PLR in different groups in terms of OS and PFS.

Results: A total of 21 included studies involving 2312 patients with advanced lung cancer receiving immunotherapy were included. The combined results suggested that elevated PLR was associated with poorer OS (HR=2.24; 95% CI: 1.87-2.68; I² =44%; P=0.01) and PFS (HR=1.66; 95% CI: 1.36-2.04; I² =64%; P<0.01). Furthermore, elevated PLR showed a lower ORR (OR= 0.61; 95% CI: 0.43-0.87, I²=20%; P=0.29) and DCR (OR= 0.44; 95% CI: 0.27-0.72, I²=61%; P=0.02). In subgroup analyses, pretreatment PLR was significantly associated with adverse OS and PFS. The same results were observed in different PLRs in terms of cutoff value (>200 vs. ≤200). Furthermore, high PLR was significantly associated with poor OS and PFS in advanced non-small cell lung cancer (NSCLC); however, PLR was not associated with OS and PFS in advanced small cell lung cancer (SCLC). In addition, PLR predicted poor OS irrespective of regions and types of immune checkpoint inhibitors (ICIs).

Conclusion: On the whole, patients with low PLR had better OS and PFS, as well as higher ORR and DCR when receiving immunotherapy in advanced lung cancer especially for advanced NSCLC. And further investigations are warranted to confirm the prognostic value of PLR in advanced SCLC.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022315976.

Keywords: advanced lung cancer; biomarker; immune checkpoint inhibitor; immunotherapy; meta-analysis; platelet to lymphocyte ratio; prognosis.

Figure 1

Flow diagram of the selection of the included studies.

Figure 2

Meta-analysis of the relationship between different comparative models of the platelet to lymphocyte ratio (PLR) and response. (A) Meta-analysis of the relationship between PLR and objective response rate (ORR); (B) Meta-analysis of the relationship between PLR and disease control rate (DCR).

Figure 3

Meta-analysis of the relationship between different comparative models of the platelet to lymphocyte ratio (PLR) and overall survival (OS).

Figure 4

Meta-analysis of the relationship between different comparative models of the platelet to lymphocyte ratio (PLR) and progression-free survival (PFS).

Figure 5

Subgroup analyses of the associations between the platelet to lymphocyte ratio (PLR) and overall survival (OS) and progression-free survival (PFS). *Immunotherapy means these articles reporting different types of ICIs or no detailed types of ICIs.

Figure 6

Sensitivity analyses and publication bias. (A) Sensitivity analysis of overall survival (OS); (B) A trim and fill funnel plot of overall survival (OS); (C) Sensitivity analysis of progression-free survival (PFS); (D) A trim and fill funnel plot of progression-free survival (PFS).