The 2012 edition of the NCCN clinical practice guidelines for non-small cell lung cancer has been revised extensively and has many highlights, such as adjustments in surgery, pathological staging, genetic testing, and drug therapy. Through the updates, we also see that the individualized treatment of NSCLC has become more standardized and improved. In this article, we will explain some of the updates. Update 1 VATS is included in the standard treatment of early-stage lung cancer Television thoracoscopic surgery (VATS), also known as thoracoscopic lobectomy, is considered a revolutionary breakthrough in thoracic surgery at the end of the 20th century and is the most widely used thoracoscopic procedure in minimally invasive thoracic surgery. There is no significant difference in operation time, intraoperative bleeding and number of intraoperative lymph node dissection between VATS and open thoracic surgery, and its advantages include less trauma, protection of lung function, less postoperative pain, faster postoperative recovery, shorter hospitalization time, lower cost, and superiority for high-risk patients. Superiority exists. The current evidence-based medical evidence shows that the efficacy of VATS for stage I peripheral NSCLC is not significantly different from that of traditional open-heart surgery. one of the main directions for the future development of surgical treatment of lung cancer. In early 2011, the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) published a new international multidisciplinary classification standard for adenocarcinoma of the lung. This classification standard takes into account the updated understanding of lung adenocarcinoma by different disciplines and is the first classification based on an integrated multidisciplinary platform. One of the major changes in the new criteria is the elimination of the concept of fine bronchoalveolar carcinoma, as the term was used in five different types of adenocarcinoma, causing much confusion in clinical diagnosis and research. The 2012 edition of the NCCN guidelines also adopts new classification criteria for adenocarcinoma: adenocarcinoma in situ (AIS), microinvasive adenocarcinoma (MIA), invasive adenocarcinoma, and invasive adenocarcinoma variant. “Adenocarcinoma in situ” is a new classification of adenocarcinoma, which is a small adenocarcinoma (≤3 cm) with limited squamous growth of tumor cells along the alveolar wall without interstitial, vascular or pleural infiltration. This new term will replace the term “bronchoalveolar carcinoma” and is the most important update to the pathology section of the 2012 NCCN guidelines. The 2012 edition of the NCCN guidelines recommends ALK testing for patients with adenocarcinoma, large cell carcinoma, and stage NO NSCLC as a Class 2A recommendation. In contrast, EGFR mutation testing and ALK testing are not routinely recommended for patients with squamous carcinoma. Among the pathology principles, the NCCN recommends fluorescence in situ hybridization (FISH) for detection of EML4-ALK fusion genes in NSCLC. Although polymerase chain reaction (PCR) and immunohistochemistry (IHC) are still being evaluated, FISH is superior to both and is currently considered the “gold standard”, with the great advantage that commercial probes are now available for the diagnosis of ALK rearrangements. Therefore, the FISH test will help identify lung cancer patients who may benefit from crizotinib treatment. Although certain characteristics of EML4-ALK-positive patients (e.g., adenocarcinoma, non-smoking or light smoking) are similar to those with EGFR mutations, ALK-positive patients are resistant to EGFR TKIs. 2012 edition of the NCCN guidelines state that EGFR mutations and ALK rearrangements are often mutually exclusive and that for patients who are ALK-positive but crizotinib-resistant, second-line therapy given with erlotinib or gefitinib is ineffective. Update 4 Crizotinib Joins First-Line Treatment The 2012 edition of the NCCN guidelines recommends crizotinib as a first-line treatment option for patients with ALK-positive NSCLC. In recent years, EML4-ALK has become a new favorite in targeted therapy research. In NSCLC patients, the positive rate of ALK rearrangement is about 3% to 5%, and the odds of EML4-ALK fusion are high in patients with adenocarcinoma, never smokers or small smokers, and ALK-positive patients are younger but have a poorer prognosis compared to ALK-negative NSCLC patients. Crizotinib is a dual blocker of ALK and c-MET genes or their variants. Two multicenter single-arm clinical trials showed significant therapeutic activity of crizotinib in patients with ALK-positive NSCLC. One was the PROFILE 1001 study part 2 extension cohort study, which included 119 patients, with an objective remission rate (ORR) of 61% and a median duration of remission of 48.1 weeks in the crizotinib group. Another study, PROFILE 1005, enrolled 136 patients with ALK-positive advanced NSCLC who had failed prior chemotherapy (93% of patients had been treated with at least 2 or more chemotherapy regimens) from 12 countries who were treated with crizotinib. The results showed that patients had an ORR of 50% and a median duration of remission of 41.9 weeks. The most common adverse reactions observed in both studies (≥25%) were visual impairment, nausea, diarrhea, edema, and constipation. Based on the results of these two studies, the U.S. FDA approved crizotinib for the first-line treatment of locally advanced or metastatic ALK-positive NSCLC in August 2011. Is crizotinib available for second-line treatment? An ongoing randomized phase III clinical study (PROFILE1007) is currently comparing crizotinib with other second-line treatment options, and we look forward to the publication of the results. The addition of crizotinib to first-line therapy is undoubtedly a major breakthrough in targeted therapy for NSCLC patients, but despite the relatively high efficiency (>80%), patients who are effectively treated with crizotinib usually develop resistance after 1 year of treatment, so further research is needed to explore the mechanism of crizotinib resistance and how to overcome it. UPDATE 5 Maintenance therapy adds another force – gemcitabine Maintenance therapy for lung cancer has received widespread attention. With the approval of pemetrexed, gefitinib, erlotinib and docetaxel for maintenance therapy, gemcitabine is also recommended as Class 2A in the 2012 edition of NCCN guidelines for continued maintenance therapy. In 2010, M. Perol et al. published the results of the IFCT-GFPC0502 study in the journal J ournal of Clinical Oncology. This was a randomized phase III clinical study in which lung cancer patients given first-line cisplatin + gemcitabine regimen chemotherapy for 4 cycles were randomized 1:1:1 into three groups: gemcitabine maintenance, erlotinib maintenance, or observation. The results showed that PFS was significantly prolonged in the maintenance group compared to the observation group, with a particularly prominent prolongation in the gemcitabine maintenance group (3.8 months) compared to 2.9 months in the erlotinib maintenance group and 1.9 months in the observation group. a phase III randomized clinical study published by Brodowicz in Lung Cancer in 2006. comparing the efficacy of the gemcitabine continuation maintenance treatment group with the best supportive care group after first-line application of gemcitabine + cisplatin regimen, showed a slight difference in PFS but no difference in OS between the two groups. Therefore, the 2012 edition of the NCCN guidelines recommends gemcitabine as a continuation maintenance therapy, and NSCLC patients, especially those with squamous cancer, have an additional drug option for maintenance therapy. The 2012 edition of the NCCN guidelines also upgraded the recommendation level for maintenance therapy. For patients with adenocarcinoma, large cell carcinoma, and NSCLC, pemetrexed has been changed from a Class 2B recommendation to a Class 2A recommendation for maintenance therapy; erlotinib has been changed from a Class 2B recommendation to a Class 2A recommendation for maintenance therapy, and docetaxel (Class 3) has been removed. For patients with squamous carcinoma, erlotinib was changed from a Class 2B recommendation to a Class 2A recommendation in switch maintenance therapy and docetaxel was changed from a Class 3 recommendation to a Class 2B recommendation. Update 6 Other updates Second-line therapy The current remission rate for second-line therapy for lung cancer is less than 10%. For patients with PS 0 to 2 who progress on or after first-line therapy, the NCCN guidelines recommend giving docetaxel, pemetrexed, erlotinib, or a two-drug regimen containing platinum ± bevacizumab. Because crizotinib was included in the NCCN guidelines, the phrase “if erlotinib has been used as a first-line regimen and is an adenocarcinoma type” was changed to “if erlotinib or crizotinib has been used as a first-line regimen and is a non-squamous pathology type” after the platinum-containing two-drug regimen ± bevacizumab, and the recommendation level was changed from 2B “and the recommendation level was changed from category 2B to 2A. For early-stage lung cancer, the new NCCN guidelines state that: adjuvant therapy for stage IA (peripheral T1ab, N0), radical RT to radical RT or SABR for inoperable patients; stage IB (peripheral T2a, N0), stage I (central T1ab-T2a, N0), stage II (T1ab~T2ab, N1; T2b, N0), stage IIB (T3, N0), and radical RT to radical RT or SABR ± chemotherapy for inoperable patients. It is evident that SABR is an important option worth considering for all patients with early-stage lung cancer. Conclusion In recent years, the field of NSCLC has undergone radical changes, and from the changes in the NCCN guidelines this year, not only the changes in treatment strategies, but also the changes in details are very important. with the evidence-based medical evidence becoming more and more adequate, the recommendation level of NCCN guidelines has been widely agreed and gradually increased. the treatment of NSCLC has gradually entered the era of individualized treatment, with pathology, immunophenotype, Prognostic and predictive marker genes and proteins have become indicators to guide individualized treatment of lung cancer, thus “prescribing the right medicine” and improving the overall survival of patients. Of course, new driver genes are being discovered and new targeted therapeutic agents are being developed, and more exploratory studies are needed to find new therapeutic strategies.