Pathological fractures as a prognostic factor for survival in metastatic solid cancers: A meta-analysis
Ahmed Elkohail, Ali Soffar, Ahmed M. Khalifa, Ibrahim Omar, Ahmed Anber, Ashis Kumar Paul, Larisa Radu, Aqil Ahamed Mohideen Ahamed Sha, Ahmed Elsaket, Mostafa Abdulaziz, Mahmoud Teama, Ehab Sharyan, Mohamed TerraBackground
Pathological fractures (PFs) are clinically important skeletal-related events in patients with bone metastases from solid tumors and may negatively affect survival. This meta-analysis aimed to quantify the association between PFs and overall survival (OS) in patients with metastatic solid cancers.
Methods
This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 using a PICOS-defined protocol. PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 2025 without language restrictions. Eligible studies included adults with metastatic solid tumors, compared patients with and without PFs, and reported OS using hazard ratios (HRs). Tumor types were pooled a priori because the included studies evaluated the same exposure-comparator-outcome framework across metastatic solid tumors. Random-effects models were used, and heterogeneity was explored through moderator analyses and meta-regression. Two reviewers independently screened records, extracted data, and assessed risk of bias using MINORS for observational studies and the Cochrane tool for randomized trials.
Results
From 198 records, four studies comprising seven cohorts and 3,607 participants met the inclusion criteria. Random-effects pooling showed that PFs were significantly associated with poorer OS compared with no PFs (pooled HR 1.40, 95% CI 1.08–1.81; p = 0.010). However, heterogeneity was substantial (I 2 = 92.6%), indicating that the pooled estimate should be interpreted cautiously. Meta-regression suggested a positive association between publication year and effect size (β = 0.041; p = 0.041), whereas primary cancer subgrouping was not a significant moderator. Funnel-plot asymmetry and Egger’s test suggested possible small-study effects.
Conclusions
PFs appear to be associated with worse OS in patients with metastatic solid tumors, highlighting the importance of fracture prevention, early identification of impending fractures, and multidisciplinary care. Nevertheless, the small evidence base, substantial heterogeneity, and possible publication bias warrant cautious interpretation. Prospective studies with standardized PF definitions and adjusted survival analyses are needed.