Oligometastatic Disease (OMD): The Classification and Practical Review of Prospective Trials

SIMPLE SUMMARY: Oligometastatic disease (OMD) is currently recognized as an intermediate state of cancer between the localized and widely metastatic form of the disease. Before the term OMD was introduced into practical oncology, metastatic lesions were considered markers of the systemic disease and the majority of such patients received systemic therapies that were usually associated with a broad spectrum of adverse side effects. After the concept of the OMD state of cancer was introduced into the clinic and accepted by oncologists, different treatment options became available. Given no OMD biomarkers are currently available, the diagnosis of OMD is based exclusively on imaging findings. Based on this data, different clinical scenarios have become available that are associated with different treatment strategies and clinical outcomes. Some of clinical studies illustrated a significant improvement in the overall survival (OS) and progression-free survival (PFS) rates of cancer patients who received local aggressive therapies (e.g., stereotactic body radiotherapy (SBRT)). Such therapies are generally well-tolerated and provide good local control of the disease. Moreover, local therapies can be used to delay systemic therapies in the context of metachronous disease. We discuss here the current classification and management strategies in OMD and review the prospective and ongoing clinical trials. ABSTRACT: Oligometastatic disease (OMD) is currently known as an intermediate state of cancer, characterized by a limited number of systemic metastatic lesions for which local ablative therapy could be curative. Indeed, data from multiple clinical trials have illustrated an increase in overall survival (OS) for cancer patients when local ablative therapy was included in the systemic adjuvant therapy. Given that no driver and somatic mutations specific to OMD are currently established, the diagnosis of OMD is mainly based on the results of X-ray studies. In 2020, 20 international experts from the European Society for Radiotherapy and Oncology (ESTRO) and the European Organization for Research and Treatment of Cancer (EORTC) developed a comprehensive system for the characterization and classification of OMD. They identified 17 OMD characteristics that needed to be assessed in all patients who underwent radical local treatment. These characteristics reflect the tumor biology and clinical features of the disease underlying the development of OMD independently of the primary tumor type and the number of metastatic lesions. In particular, the system involves the characteristics of the primary tumor (e.g., localization, histology, TNM stage, mutational status, specific tumor markers), clinical parameters (e.g., disease-free interval, treatment-free interval), therapies (e.g., local, radical or palliative treatment, the numbers of the therapeutic regimens), and type of OMD (e.g., invasive). Based on the aforementioned criteria, an algorithm was introduced into the clinic to classify OMDs collectively according to their nomenclature. A history of polymetastatic disease (PMD) prior to OMD is used as a criterion to delineate between induced OMD (previous history of PMD after successful therapy) and genuine OMD (no history of PMD). Genuine OMD is divided into two states: recurrent OMD (i.e., after a previous history of OMD) and de novo OMD (i.e., a first newly diagnosed oligometastatic disease). de novo OMD is differentiated into synchronous and metachronous forms depending on the length of time from the primary diagnosis to the first evidence of OMD. In the case of synchronous OMD, this period is less than 6 months. Lastly, metachronous and induced OMD are divided into oligorecurrence, oligoprogression, and oligopersistence, depending on whether OMD is firstly diagnosed during an absence (oligo recurrence) or presence (oligoprogression or oligopersistence) of active systemic therapy. This classification and nomenclature of OMD are evaluated prospectively in the OligoCare study. In this article, we present a practical review of the current concept of OMD and discuss the available prospective clinical trials and potential future directions.