Platelet-derived biomarkers in solid malignancies: a systematic review and meta-analysis of prognostic outcomes and...

Platelets contribute to tumor angiogenesis, immune evasion, and metastasis, and baseline platelet indices have been proposed as accessible prognostic biomarkers for solid malignancies. Their clinical utility remains uncertain because prior studies have reported inconsistent comparison directions and cancer type-dependent effects. This PRISMA 2020-compliant, PROSPERO-registered (CRD420261350460) systematic review and meta-analysis evaluated platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in patients with solid malignancies. Overall survival (OS) was the primary endpoint for all indices, and disease-free survival (DFS) was the secondary endpoint for PLT and PDW. Studies were pooled using Hartung-Knapp random-effects models, and diagnostic and secondary biomarker categories were synthesized narratively. Of the 29 included studies, 22 contributed to the quantitative synthesis. Pooled PLT-OS was significantly adverse (HR 1.41, 95% CI 1.11-1.79) following exclusion of two studies whose platelet count estimates were not exposure-comparable to the remaining cohorts; the direction-specific high-versus-low PLT estimate was similarly adverse (HR 1.22, 95% CI 1.04-1.42). High-versus-low MPV was significantly associated with adverse overall survival (HR 1.34, 95% CI 1.16-1.55, I² = 0%); the non-directional pooled MPV-OS estimate was not robust to publication bias (trim-and-fill-adjusted HR 1.05, 95% CI 0.85-1.29). The PDW-OS (HR 1.95, 95% CI 0.51-7.43) and PCT-OS (HR 1.55, 95% CI 0.22-10.92) were not significant. PLT-DFS was significantly adverse (HR 1.51, 95% CI 1.10-2.08), whereas PDW-DFS was not (HR 1.17, 95% CI 0.53-2.59). GRADE certainty was moderate for PLT and MPV, low for PDW, and very low for PCT. Diagnostic evidence was synthesized narratively because of substantial methodological and clinical heterogeneity; combined biomarker and machine-learning models generally showed better discriminatory performance than standalone platelet indices. Both PLT and MPV were independently associated with adverse overall survival in direction-specific analyses, while PDW and PCT lack support. Diagnostics remain narrative pending validation. Standardized prospective multicenter studies are required.