SARIFA and Lipid Metabolic Reprogramming in Prostate Cancer: Fundamental Mechanisms, Tumor Microenvironment, and Novel Biomarker Prospects.

Prostate cancer (PCa) is one of the most prevalent malignancies in men worldwide. Established clinicopathological parameters do not fully describe the biological heterogeneity of PCa or consistently predict its clinical course after radical prostatectomy, supporting the investigation of additional prognostic markers. Stroma AReactive Invasion Front Areas (SARIFA) is a recently described histomorphological pattern characterized by direct contact between tumor cells and adipocytes without intervening desmoplastic or inflammatory stroma at the invasion front. Limited retrospective evidence from prostatectomy specimens indicates that SARIFA positivity is associated with adverse pathological features. However, its independent prognostic value and clinical utility remain to be established. Because SARIFA can potentially be assessed on routinely prepared hematoxylin and eosin-stained sections without additional molecular assays or immunohistochemical staining, it represents a potentially accessible candidate marker, although its reproducibility, standardization, and cost-effectiveness require formal evaluation. This review summarizes current evidence concerning lipid metabolic remodeling and tumor-adipocyte interactions that may contribute to the SARIFA phenotype in PCa. Androgen receptor-regulated lipid metabolism, uptake of adipocyte-derived fatty acids, adipokine signaling, and extracellular vesicle-mediated communication provide a plausible mechanistic framework. Nevertheless, direct experimental evidence linking several of these processes specifically to SARIFA in PCa remains limited, and some proposed relationships are based on indirect evidence or findings from other tumor types. Further studies should establish standardized scoring criteria, intra- and interobserver reproducibility, external validation, and incremental prognostic value before the clinical implementation of SARIFA can be considered.