Beyond the primary site: Molecular insights and clinical implications of cancer metastatic overlap between lung and urological organ cancers (Review).

Metastasis between primary lung cancers and urological malignancies, for example prostate, renal and bladder cancers, poses diagnostic and therapeutic challenges. Previous epidemiological data underscore a frequent bidirectional overlap that adversely affects patient survival. This review synthesizes current molecular insights and clinical implications of this metastatic crosstalk, delineating how these distinct tumor types exploit shared molecular toolkits, including the C‑X‑C chemokine receptor 4/C‑X‑C motif chemokine ligand 12 axis, hepatocyte growth factor/mesenchymal‑epithelial transition factor signaling and epithelial‑mesenchymal plasticity, to facilitate dissemination and colonization. The distinct immune contextures and cellular architectures of the metastatic niche in different organs have also been explored, revealing their notable influence on therapeutic responses. Although molecular profiling and liquid biopsies have been refining diagnostic precision and allowing for a shift toward mechanism‑centric agnostic therapies, organ‑specific microenvironments continue to modulate drug efficacy. Integration of these insights is necessary for advancing personalized management strategies and improving outcomes for patients in this complex clinical setting.