Immune-inflammatory indices as predictors of pathologic complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review and meta-analysis of observational studies

BACKGROUND: Achieving a Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) is associated with improved survival and organ preservation. Available blood-based inflammatory indices may help predict pCR and guide individualized treatment. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a comprehensive search of PubMed, Web of Science, Scopus, and Embase, and Cochrane Library to identify studies including adult patients with pathologically confirmed LARC treated with nCRT followed by total mesorectal excision. Included studies reported categorical analyses of pre-nCRT neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), or systemic immune-inflammation (SII) in relation to pCR. Random-effects models were used to generate pooled odds ratios for high versus low index values. Heterogeneity, small-study effects, meta-regression, and the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE framework were also assessed. RESULTS: Twenty-four studies including 6,572 patients (20 evaluating NLR, n = 6,110; 12 PLR; n = 4,601; and 5 SII, n = 1,340) met the inclusion criteria and all were rated as high quality according to the Newcastle–Ottawa Scale. Higher pre-nCRT NLR was associated with reduced odds of pCR (pooled OR 0.60, 95% CI 0.49–0.71; I²=35.4%). High PLR similarly predicted lower pCR rates (pooled OR 0.53, 95% CI 0.37–0.69; I²=54.7%), as did higher SII (pooled OR 0.42, 95% CI 0.26–0.58; I²=27.9%). Associations were consistent across cut-off values and geographic regions. Meta. Meta-regression suggested that age, sample size, cut-off value/determination methods, tumor stage, statistical adjustment (unadjusted vs. adjusted), geographic region and other potential confounders partially explained the between-study heterogeneity. CONCLUSIONS: Elevated pre-nCRT NLR and PLR were associated with lower odds of achieving pCR in patients with LARC. The evidence regarding SII was limited and should be interpreted with caution. These inexpensive and available inflammatory indices may potentially refine pre-nCRT risk stratification and identify candidates who may benefit form organ-preservation approaches.