Lung cancer remains the number one cancer killer worldwide. Whereas once we knew nothing about lung cancer treatment, through scientific research and development over the past decades, the treatment and management paradigm of lung cancer has changed and advanced dramatically. From macroscopic to microscopic, from radiotherapy to targeted therapy to immunotherapy. Today, let’s review these 43 years of lung cancer treatment development from 1973 to 2016 through this article. Early screening for lung cancer: from macroscopic to microscopic The National Cancer Institute designed a randomized trial in 2000 to study which method of “quarterly sputum cytology screening” or “annual chest x-ray screening” could detect early lung cancer and reduce the mortality rate of lung cancer, and found that these two methods of early screening prolonged survival but failed to reduce the mortality rate of lung cancer. In 2001, it was reported that low-dose computed tomography (CT) of the chest could improve the detection rate of small lung nodules and that the 5-year survival rate of patients who were screened early was very high. Subsequently, the National LungScreeningTrial (NLST) demonstrated that low-dose CT scans reduced lung cancer mortality by 20% compared to x-ray screening. In recent years, early lung cancer screening and identification of lung nodules can also be performed using sputum, blood, bronchial brushes, and exhaled gas for a variety of molecular and cytological analyses, and not just epidemiology, but also to understand the pre-evolutionary process of lung cancer by analyzing chromosomal alterations, gene expression, microRNA expression, and volatile organic compounds. Prevention: Smoking cessation is still the only effective intervention available In 1964, the Surgeon General of the United States issued a report; there is a definite relationship between smoking and lung cancer, and people should cut down on smoking. The damage of smoking to lung cancer is well known: the incidence of lung cancer in smokers is increasing year by year, and the recurrence rate of lung cancer after surgery is increasing at a rate of nearly 2% per year, although the incidence of lung cancer in non-smokers is increasing in recent years, the incidence of lung cancer in people with a history of smoking is still 10% higher. Professor Doll published a study in 1976; lung cancer prevalence: persistent smokers > quitters by age 30 > never smokers, so it is important to quit smoking early (especially before age 30). In addition, timely smoking cessation in patients with diagnosed lung cancer who smoke significantly prolongs survival. Smoking cessation is the only known effective intervention. In recent years, preclinical trials have shown that iloprost is effective in preventing lung cancer – the only drug that has been shown to improve bronchial heterotypic hyperplasia in phase II trials. Long-term trials using lung cancer as a study endpoint are currently underway to evaluate the effectiveness of Iloprost for lung cancer chemoprevention. Pathologic Staging: The 8th edition is hot off the presses The International Association for the Study of Lung Cancer has improved the pathologic staging of lung cancer this year. For example, the previous bronchoalveolar carcinoma is now classified as adenocarcinoma in situ, invasive carcinoma, and microinvasive carcinoma. The International Association for the Study of Lung Cancer revised the old TNM staging criteria and released the eighth edition of the TNM staging criteria, which came into effect on January 1, 2017. The staging is more detailed, making the prognosis of patients with different stages more distinct and helping to select better treatment options. Surgery: continuous progress The application of thoracoscopic surgery: reduction of postoperative pain; segmental or wedge resection: increased success rate of small nodule resection; Masako develops the use of robotic surgical techniques, PK traditional thoracoscopic surgery: efficacy geometry, expect results to be revealed. Radiotherapy: new indications, new tools Radiotherapy for stage IIIA/N2 lung cancer: in early stage lung cancer, postoperative radiotherapy can have detrimental effects and can be beneficial in patients with stage IIIA/N2 lung cancer. New radiotherapy techniques have reduced toxicity at this stage, and many patients with stage IIIA/N2 lung cancer can achieve good results using a triple therapy approach of surgical chemotherapy radiotherapy. Stereotactic radiation (SBRT): The efficacy of SBRT for treating microscopic lesions is similar to that of surgical resection, so SBRT can be an alternative to surgical resection of microscopic lesions; it can also be used for palliative treatment. Clinical trials are currently underway to study the use of SBRT for the treatment of oligometastatic disease. In addition, brain stereotactic radiotherapy is commonly used to treat brain metastases and can prolong survival and reduce radiotherapy-related side effects compared to whole brain radiotherapy. Chemotherapy: NSCLC and SCLC Chemotherapy was the first treatment to significantly prolong the survival of patients with progressive small cell lung cancer (SCLC). Since the 1980s, the two-drug combination of etoposide combined with platinum has been the standard of care for SCLC, being more effective and less toxic than three-drug combinations. In limited-stage SCLC, the combination of chest radiation and chemotherapy is superior to radiation or chemotherapy applied alone. A 70 Gy once-daily dose of radiotherapy is less effective than a 45 Gy twice daily dose of radiotherapy, and the combination of chemotherapy and radiotherapy is better than sequential therapy. In extensive stage SCLC, chest radiotherapy after chemotherapy in patients who have responded to chemotherapy can achieve better outcomes, but it has not yet become standard therapy and needs to be proven in other randomized trials. Prophylactic head radiotherapy after induction chemotherapy for either limited-stage or progressive SCLC can reduce the incidence of brain metastases and can prolong survival, with a recommended total radiotherapy dose of 25 Gy to reduce the incidence of central nervous system side effects. Existing studies in non-small cell lung cancer (NSCLC) have shown that platinum-based two-drug combination chemotherapy is more effective than placebo or single-drug chemotherapy, with no difference in efficacy between platinum classes. In addition, pemetrexed was more advantageous for adenocarcinoma, while gemcitabine was more therapeutic for squamous carcinoma. Targeted therapy: a new battlefield for lung cancer treatment 1. Anti-angiogenesis In first and second line treatment, the use of anti-vascular endothelial growth factor (VEGF) bevacizumab or anti-vascular endothelial growth factor receptor (VEGFR) ramolutumab in combination with chemotherapy can prolong overall survival. Bevacizumab, which is less effective in non-squamous cancers, and in combination with chemotherapy did not improve survival in patients with non-squamous cancers. Nedanib, which is both an anti-VEGFR and multiple tyrosine kinase inhibitor (TKI), can prolong the survival of non-squamous cancer patients in combination with second-line chemotherapy regimen. 2. EGFR mutations EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have achieved dramatic breakthroughs in the efficacy of a small group of patients. Comparing the efficacy of three EGFRTKIs (gefitinib, erlotinib, or afatinib) with platinum-based chemotherapy for NSCLC in patients with EGFR mutations. EGFRTKIs beat chemotherapy as the first-line treatment for EGFR-mutated NSCLC (higher ORR, longer PFS, lower toxicity, better quality of survival). Unfortunately, lung cancer is still not curable because all lung cancers eventually undergo tumor progression, most commonly due to mutational resistance. 50-60% of resistance is in patients with T790M locus mutations, and the third-generation TKIs oseltinib can improve ORR after resistance to erlotinib and gefitinib due to T790M mutations. therefore, when deciding whether to use oseltinib after failure of first-line targeted therapy When second-line treatment is performed, the patient must know the T790M mutation, and if it occurs, the patient can switch to oseltinib. 3.ALK gene mutation The proportion of ALK mutation in NSCLC is about 3% to 5%. Crizotinib is the most effective drug for treating ALK-positive cancer patients, and ALK gene testing must be done before taking it. For this type of patients, ORR reaches about 50%, and longer PFS can be obtained compared with chemotherapy. 4.Other In addition to ALK gene mutation, lung cancer patients may also have ROS1, MET, BRAF (V600E), HER2, RET gene mutations, drugs targeting the above genes are still in clinical trials and are not listed in China. PD-L1) or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as the target for immunosuppression to exert anti-tumor effects. The FDA has approved the anti-PD-1 antibodies nivolumab and pembrolizumab for the second-line treatment of NSCLC. phase 2 clinical trials have found that anti-PD-L1 antibodies such as atezolizumab and durvalumab are more effective than docetaxel, and phase 3 clinical trials are underway regarding the efficacy of these two drugs.