# Platelet-to-lymphocyte ratio for prognostication in immune checkpoint inhibitor-treated cancer patients: a meta-analysis of 13027 patients highlighting nivolumab-responsive renal cell carcinoma

## TL;DR

This study finds that a high platelet-to-lymphocyte ratio is linked to worse survival in cancer patients treated with immune checkpoint inhibitors, especially in those with renal cell carcinoma treated with nivolumab.

## Contribution

The study is the first to systematically analyze PLR's prognostic value across multiple cancer types and ICI classes, highlighting unique associations in nivolumab-treated renal cell carcinoma.

## Key findings

- Elevated PLR is a strong predictor of shorter overall and progression-free survival in ICI-treated cancer patients.
- PLR's prognostic value is most pronounced in hepatocellular, esophageal, and head and neck cancers, and in camrelizumab-treated gastrointestinal tumors.
- Nivolumab-treated renal cell carcinoma patients with high PLR show uniquely worsened survival outcomes.

## Abstract

To assess platelet-to-lymphocyte ratio (PLR) prognostic utility for overall (OS) and progression-free survival (PFS) in immune checkpoint inhibitor-treated cancer patients, and examine impacts of geography, cancer type, cutoff, ICI class, treatment line and stage.

A systematic literature search identified studies investigating PLR and prognosis in ICI treated patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup analyses examined key covariates; publication bias was assessed.

Analysis of 98 publications (86 OS, 72 PFS) demonstrated that elevated PLR was a robust predictor of shorter OS (HR 1.79, 95% CI: 1.60-2.00) and PFS (HR 1.60, 95% CI: 1.44-1.78). Subgroup analyses revealed: (1) Geographic region: Asian populations exhibited the most consistent correlation with OS and the highest PFS risk (69%). (2) Cancer type: For OS, prognostic value was maintained across all cancers; the most pronounced impacts were observed in hepatocellular carcinoma (HR 2.10), esophageal carcinoma (HR 2.08), and head and neck squamous cell carcinoma (HR 2.61). For PFS, a notable link to poor outcomes was observed in NSCLC and hepatocellular carcinoma, whereas renal cell carcinoma showed no such correlation. (3) PLR cutoff: both PLR ≥180 (OS: HR 1.87; PFS: HR 1.68) and PLR <180 (OS: HR 1.73; PFS: HR 1.53) subgroups consistently yielded unfavorable outcomes. (4) ICI category: for OS, camrelizumab showed the strongest prognostic relevance (HR 4.68), whereas for PFS, all ICIs yielded consistent results. (5) Treatment line: both first-line (OS: HR 1.98; PFS: HR 1.93) and second-line or beyond (OS: HR 1.87; PFS: HR 1.79) demonstrated clear prognostic utility without inter-subgroup differences. (6) Tumor stage: Advanced stages (III–IV, IIIB–IV, IV) confirmed the predictive value of PLR for both OS and PFS. (7) Cancer Subtypes: PLR remained prognostic in nivolumab-treated, stage IV genitourinary cancers; correlated with survival in pembrolizumab-treated but not nivolumab-treated NSCLC; and remained predictive in camrelizumab-treated/advanced gastrointestinal tumors. Notably, elevated PLR was uniquely associated with worsened OS and PFS in nivolumab-treated renal cell carcinoma.

Elevated PLR is consistently associated with shortened OS across the cancer types receiving ICIs, while its prognostic value for PFS fluctuates depending on cancer type and ICI class. The prognostic impact of PLR is particularly robust in the nivolumab-treated RCC, pembrolizumab-treated NSCLC, camrelizumab-treated gastrointestinal tumors, and various advanced-stage malignancies.

https://www.crd.york.ac.uk/prospero/.