Prognostic Nutritional Index and Cancer Prognostic Outcomes: An Umbrella Review of Systematic Reviews and Meta-analyses of Observational Studies

Prognostic nutritional index (PNI) has been widely investigated as a predictor of outcomes in patients with cancer; however, a comprehensive synthesis evaluating the breadth, methodological quality, and certainty of this evidence is lacking. We aimed to systematically review and critically appraise existing meta-analyses on the association between PNI and cancer prognostic outcomes. We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from database inception through 28 February, 2025. Methodological quality of included systematic reviews and meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. The protocol was registered prospectively on the International Platform of Registered Systematic Review and Meta-analysis Protocols platform (INPLASY2025110096). A total of 64 systematic reviews and meta-analyses, comprising 265 quantitative syntheses, were included. Of these, 224 (84.5%) reported statistically significant quantitative syntheses (P < 0.05) under random-effects models. AMSTAR assessment classified 44 (68.8%) systematic reviews and meta-analyses as high quality. GRADE evaluation indicated that 121 (45.7%) quantitative syntheses were supported by high-certainty evidence. Elevated PNI was consistently associated with improved overall survival (OS) across both pan-cancer and cancer-specific analyses. In pan-cancer populations, higher PNI was significantly associated with longer OS, prolonged progression-free survival, and higher objective response rates. Significant prognostic benefits of elevated PNI for OS were also observed in specific malignancies, including pancreatic cancer, gastric cancer, advanced-stage lung cancer, and glioma. Although a higher PNI is robustly associated with favorable prognostic outcomes in diverse cancers, marked heterogeneity in PNI cutoff values across studies underscores the urgent need for standardized, population-specific thresholds validated through prospective diagnostic accuracy studies.