International consensus on severe lung cancer-the first edition.

Abstract

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.