Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives

SIMPLE SUMMARY: Oligometastatic disease is a condition in oncology where cancer affects only a few distant sites. It is associated with a low-burden spread and a more favorable prognosis compared to polymetastatic disease. Recent studies have identified specific molecular and genetic features that underlie the oligometastatic phenotype, including reduced cancer cell migration and invasion ability, and an enhanced immune response in the metastatic microenvironment. Understanding these characteristics could suggest innovative personalized therapies and contribute to improving the understanding of complex cancer–host relationships. This scoping review highlights new clinical, biological, and methodological challenges that characterize this fascinating field from a modern and innovative perspective. By shedding light on the unique features of oligometastatic disease, we aim to promote the development of more effective and tailored treatments for patients with this condition. ABSTRACT: Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as “oligometastatic disease” (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.