The Road to Dissemination: The Concept of Oligometastases and the Barriers for Widespread Disease

SIMPLE SUMMARY: Oligometastatic disease is an intermediate state of metastatic dissemination with a limited number of metastatic sites and extent of disease. Tumor cells need multiple capabilities in order to migrate, survive and evolve to macroscopic metastases. These capabilities are acquired by evolutionary mechanisms and are associated with several clinical factors and biomarkers. Better understanding of these properties and biomarkers may help to select patients that can benefit from local ablative therapies, which have shown to be a promising approach in recent clinical evidence. ABSTRACT: Over the last years, the oligometastatic disease state has gained more and more interest, and randomized trials are now suggesting an added value of stereotactic radiotherapy on all macroscopic disease in oligometastatic patients; but what barriers could impede widespread disease in some patients? In this review, we first discuss the concept of oligometastatic disease and some examples of clinical evidence. We then explore the route to dissemination: the hurdles a tumoral clone has to overtake before it can produce efficient and widespread dissemination. The spectrum theory argues that the range of metastatic patterns encountered in the clinic is the consequence of gradually obtained metastatic abilities of the tumor cells. Tumor clones can obtain these capabilities by Darwinian evolution, hence early in their genetic progression tumors might produce only a limited number of metastases. We illustrate selective dissemination by discussing organ tropism, the preference of different cancer (sub)types to metastasize to certain organs. Finally we discuss biomarkers that may help to distinguish the oligometastatic state.