Phosphaturic Mesenchymal Tumors and Tumor-Induced Osteomalacia: A Systematic Review and Meta-Analysis of Clinicopathological, Molecular, and Therapeutic Paradigms

Introduction: Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms frequently overlooked in the differential diagnosis of refractory hypophosphatemia and osteomalacia. Despite their clinical significance, a comprehensive synthesis of evidence on diagnostic accuracy, therapeutic outcomes, and prognostic factors remains lacking, with current literature fragmented across small case series and heterogeneous methodologies. This gap impedes the development of standardized clinical pathways for timely diagnosis and effective management. Objective: To systematically evaluate and meta-analyze the best available evidence on the clinicopathological features, diagnostic performance of imaging modalities, and treatment outcomes in patients with tumor-induced osteomalacia (TIO) secondary to PMTs. Methods: A PRISMA-compliant systematic review and meta-analysis was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library. Peer-reviewed case series (≥3 patients) published in English were included. Data extraction focused on tumor localization, biochemical response, imaging accuracy, and surgical outcomes. Random-effects models were used for pooled estimates, with heterogeneity assessed via I2 and Cochran Q. Sensitivity and publication bias analyses ensured robustness. Results: Ten studies encompassing 1,176 patients were analyzed. Complete surgical resection yielded a high rate of biochemical remission, with consistent results across sensitivity analyses. 68Ga-DOTATATE PET/CT demonstrated superior diagnostic sensitivity compared to conventional modalities, significantly improving tumor localization. Methodological quality was moderate to high in most studies, and funnel plot symmetry indicated minimal publication bias. Conclusion: This meta-analysis confirms that early tumor localization with advanced functional imaging and complete resection are pivotal for curing TIO. A multidisciplinary approach integrating endocrinology, radiology, and surgical oncology is essential for optimal outcomes. Keywords: Phosphaturic mesenchymal tumor, Tumor-induced osteomalacia, Systematic Review, Meta-Analysis.