Local for advanced, is this a paradox?

Transl Lung Cancer Res 2021 | http://dx.doi. org/10.21037/tlcr-20-771 Approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) present with a limited number of metastatic sites at the time of diagnosis. This pattern, called ‘oligometastatic’, is commonly defined as an intermediate state between localized and widespread disease, according to the first definition proposed by Weichselbaum and Hellman in 1995 (1). They sensed that the reduced metastatic potential, the less aggressive biology and the limited number of lesions could offer a window for the use of local therapy on each active site of disease. Therefore, patients with oligometastatic disease might represent a unique subpopulation of advanced NSCLC, possibly amenable of curative intent treatments. Accordingly, in the eighth edition of TNM classification, the M descriptor was furtherly divided into three categories: M1a defining patients with contralateral pulmonary nodule(s) or pleural involvement without extrathoracic metastases, M1b for those with a single extrathoracic metastasis, and M1c in case of multiple extrathoracic metastases, even in a single organ. Such classification is based on the improved survival rates of patients with M1a/ M1b disease as compared to those with M1c (2). Instead of being a unique entity, oligometastatic NSCLC can be further defined using a time-based classification. Indeed, while synchronous oligometastatic refers to patients whose primary tumor and a limited number of metastases occur at the same time, metachronous oligometastatic applies to clinical situations characterized by the appearance of metastases after the definitive treatment of the primary tumor. Finally, a third entity, named oligoprogressive disease, depicts those patients experiencing disease progression on a limited number of distant foci during systemic therapy, in the presence of a controlled primary tumor (3). The increasing number of available loco-regional treatment strategies, especially minimally invasive surgery and stereotactic radiotherapy, have led to the introduction of synchronous oligometastatic NSCLC as a special treatment entity in the clinical practice guidelines by European Society of Medical Oncology from 2016 (4). However, even if acknowledging this entity was a step forward in research and daily practice, the optimal management of these patients is still far from being defined. The first reason that made evidence left behind was the absence of a common definition. Consequently, clinical trials exploring loco-regional approaches in this disease entity are characterized by extreme heterogeneity regarding number of metastatic sites, type of involved organs, and staging procedures, leading to not comparable results. For this reason, the European Organization for Research and Treatment of Cancer-Lung Cancer Group (EORTCLCG) started a consensus process to find a common definition of synchronous oligometastatic disease (5,6). The work included a European survey, a systematic review and real-life case discussions. A subsequent consensus meeting established that the expression ‘long-term disease control’ should replace the term ‘cure’ in matter of disease treatment. For the definition of oligometastatic disease, a maximum number of 5 metastases in 3 different organs was proposed. This was based on a balance between the survey results (where the maximum number of lesions most frequently reported was 3) and those of the systematic review (where studies included patients with 1 to 8 distant metastases, and up to 5 sites in more than one third of trials). According to the EORTC-LCG consensus, all organs are potential oligometastatic sites, except diffuse serosal, meningeal and bone marrow involvement, as these sites cannot be treated with radical intent. Even if mediastinal lymph nodes Editorial