Consistency of Recommendations for the Diagnosis and Treatment of Non-Small Cell Lung Cancer

A Systematic Review

Zhe Zhang; Sen Yang; Yanfang Ma; Hanqiong Zhou; Xuan Wu; Jing Han; Jiabao Hou; Lidan Hao; Jonathan D. Spicer; Young Wha Koh; Mariano Provencio; Noemi Reguart; Tetsuya Mitsudomi; Qiming Wang


Transl Lung Cancer Res. 2021;10(6):2715-2732. 

In This Article

Abstract and Introduction


Background: To systematically assess the consistency of recommendations regarding diagnosis and treatment of non-small cell lung cancer (NSCLC) in clinical practice guidelines (CPGs).

Methods: We systematically searched relevant literature databases and websites to identify CPGs related to NSCLC. We extracted the general characteristics of the included guidelines and their recommendations and descriptively compared and analyzed the consistency of recommendations across the guidelines.

Results: A total of 28 NSCLC guidelines were retrieved. The recommendations covered mainly diagnosis and treatment. The recommendations in the guidelines differed substantially in various topics, such as the application of positron emission tomography (PET) and the classification of stage III. Fourteen guidelines divided stage III into two types: operable and inoperable; and the remaining 14 guidelines into three sub-stages IIIA, IIIB and IIIC. Recommendations regarding the treatment in stage III were relatively inconsistent. In driver gene (EGFR, ALK, ROS1) positive patients, targeted therapy was the most common recommendation for first-line treatment, but recommendations regarding second-line treatment varied according to the site of the mutation. In driver gene negative patients, immunotherapy was the most frequently recommended option as both first- and second-line treatment, followed by chemotherapy.

Discussion: A number of countries are devoting themselves to develop NSCLC guidelines and the process of updating guidelines is accelerating, yet recommendations between guidelines are not consistent. We adopted a systematic review method to systematically search and analyze the NSCLC guidelines worldwide. We objectively reviewed the differences in recommendations for NSCLC diagnosis and treatment between the guidelines. Inconsistency of recommendations across guidelines can result from multiple potential reasons. Such as, the guidelines developed time, different countries and regions and many more. Poor consistency across CPGs can confuse the guideline users, and we therefore advocate paying more attention to examining the controversies and updating guidelines timely to improve the consistency among CPGs. Our study had also several limitations, we limited the search to CPGs published in Chinese or English, the interpretation of recommendations is inherently subjective, we did not evaluate the details of the clinical content of the CPG recommendations. Our research presents the current status of NSCLC guidelines worldwide and give the opportunity to pay more attention to the existing gaps. Further investigations should determine the reasons for inconsistency, the implications for recommendation development, and the role of synthesis across recommendations for optimal guidance of clinical care treatment. With the continuous revision and update of the guidelines, we are confident that future guidelines will be formulated with higher quality to form clear, definite and consistent recommendations for NSCLC diagnosis and treatment.


Lung cancer is the most common type of cancer type worldwide in terms of both incidence (2.1 million new cases in 2018) and mortality (1.8 million deaths in 2018). The key cause of lung cancer is tobacco smoking, which is responsible for 63% of overall global deaths from lung cancer and for more than 90% of lung cancer deaths in countries where smoking is prevalent among both men and women.[1] The morbidity of lung cancer is however declining: the annual reduction in incidence grew from 3% between 2008 and 2013 to 5% between 2013 through 2017 in men, and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined.[2] Almost one-quarter of all cancer deaths are due to lung cancer.[2,3] Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 80% of all lung cancers. Screening of high-risk population groups, early diagnosis, individualized treatment, targeted therapy and immunotherapy have contributed to the increase in 5-year survival probability from 17.2% in 2009 to 21.7% in 2019.[4,5] However, due to different treatment options, this progress differs across countries and regions. Active promotion of the optimal treatment pathways for NSCLC will therefore improve clinical outcomes.

Clinical practice guidelines (CPGs) provide clinical practitioners a basis for decision-making, and play an important role in standardizing behavior in medical care, improving patient prognosis, and saving medical resources.[6,7] In recent years, an increasing amount of CPGs for NSCLC have been published. However, there are differences in the classifications and terms used to describe the level of evidence and the strength of the recommendations between different guidelines, which can lead to confusion and complicate the choice of the most suitable guidelines to guide clinical work.[8] Conversely, guidelines must represent the diversity and inequities in access to modern care occurring at a global level and provide support as to how to manage these issues. As well, important differences in prevalence of various NSCLC patient scenarios that occur within specific geographic areas can reasonably account for regional peculiarities of specific CPGs.

This study systematically retrieved the CPGs for NSCLC and analyzed the content of the guidelines in order to provide references for the diagnosis and treatment of NSCLC, and suggestions for the formulation of related guidelines in the future. We present the following article in accordance with the PRISMA reporting checklist (available at