Abstract
Background:
The incidence and mortality of lung cancer is the highest among malignant tumors worldwide, and it seriously threatens human life and health. Surgery is the primary radical treatment for lung cancer. However, patients often experience discomfort, changes in social roles, economic pressures, and other postsurgical challenges. These factors frequently cause various psychological disorders such as anxiety and depression, significantly diminishing the quality of life and elevating the risks of recurrence, metastasis, and mortality. Therefore, effective strategies for mental function rehabilitation should be urgently developed. Traditional Chinese medicine can significantly improve psychological function and physical symptoms after lung cancer surgery, and prolong patient survival. However, its effectiveness for mental function rehabilitation after lung cancer surgery remains unclear. This study aimed to investigate the effects of Chinese medicine on mental function recovery after lung cancer surgery through a systematic review and meta-analysis.
Methods:
This study will systematically search the following databases: PubMed, Cochrane Library, EMBASE, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure, Wanfang database, VIP database, and Chinese BioMedical Literature database. Search for studies published from the inception of each database until April 22, 2024. This study will be limited to clinical randomized controlled trials (RCTs). The primary outcome will be depression or anxiety, as indicated by the scale score. Data analysis will be performed using RevMan 5. The Cochrane Risk of Bias Assessment Tool will be used to evaluate the quality of included studies. Finally, the quality of the evidence will be classified using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) System.
Results:
This meta-analysis aims to offer comprehensive evidence of the effectiveness of traditional Chinese medicine in mental function rehabilitation after lung cancer surgery. The study will assess the quality of the reports and conduct a subgroup analysis based on various postoperative stages, intervention measures, intervention duration, and sex to gather more evidence to fill the gap in psychological function rehabilitation after lung cancer surgery. These data can be used to guide clinical practice and inform future studies. More importantly, the results of this study will provide evidence to support the development of expert consensus and clinical guidelines in the field of mental function rehabilitation after lung cancer surgery.
Introduction
The Global Cancer Data 2022 statistics show that nearly 20 million new cancer cases have been reported worldwide. Among these, lung cancer is the most frequently diagnosed, accounting for 12.4% of all cancers (2.48 million cases). Additionally, lung cancer is also the leading cause of cancer-related deaths, accounting for 18.7% (1.8 million) cancer-related deaths. 1 Currently, radical surgery is one of the most effective treatments for lung cancer. In general, access to surgery increases the likelihood of a cure, leading patients to feel more optimistic and hopeful, with lower levels of anxiety and depression. 2 However, clinical studies have found that patients with lung cancer who have undergone surgery often experience psychological disorders such as depression, anxiety, shame, and guilt.3,4 The prevalence of anxiety and depression increased from 8% to 9% and 12% to 19%, 5 respectively. Compared to patients with other cancers, those with lung cancer often experience more psychological pressure and stigma, leading to poorer mental health.6,7
A six-month prospective study found that approximately 29% of patients with lung cancer experience depression after thoracotomy. Patients with lung cancer and emotional problems have a lower quality of life (QOL) and heavier symptom burden than patients without emotional problems (P < .05).8,9 In addition, residual pain and dyspnea were significantly correlated with postoperative depression, while dyspnea was significantly correlated with postoperative anxiety (P < .01). 5 Anxiety and depression were associated with reduced disease-free survival (DFS) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. 3 Compared to individuals without depression, those with depression had a 17% higher mortality rate. The median survival estimates were reduced by approximately 200 days and the risk of death was 50% higher in individuals with newly diagnosed and persistent depression. 10 Adverse psychological states can also disrupt the tumor microenvironment and decrease treatment compliance and overall rehabilitation effectiveness in patients with lung cancer after surgery, potentially leading to suicidal tendencies.11,12 Moreover, psychological stress impairs the ability of iNKT cells to trigger IL-4 and IFN-γ production, forcing them to promote atypical systemic inflammatory features. 13 This can accelerate the development and spread of cancer cells. Therefore, anxiety, depression, and other psychological disorders are closely associated with the clinical symptoms and prognosis of patients with lung cancer after surgery. Psychological function rehabilitation in these patients is a key clinical issue.
Currently, psychological rehabilitation methods for patients with lung cancer mainly involve psychosocial and drug interventions. 14 However, patients often express concerns about being stigmatized for having a mental illness after undergoing psychological treatment, which leads them to resist treatment. In addition, some anti-anxiety and anti-depression drugs interact with tumor treatment-related drugs, leading to neurotoxicity, addiction, and other adverse reactions due to the lack of medication guidance. 15 Therefore, the implementation of these interventions is often restricted. Previous studies have found that traditional Chinese medicine (TCM) can improve the psychological well-being of patients with lung cancer by alleviating depression and anxiety, reducing postoperative discomfort, increasing compliance, and enhancing treatment tolerance.16,17 For example, Shenlingcao oral liquid (SOL) can significantly improve the psychological status of patients undergoing adjuvant chemotherapy after radical lung cancer surgery and reduce tumor-related symptoms for at least 6 months. 18 In addition, compared with the follow-up observation group, the comprehensive treatment program involving TCM can increase the improvement rate of clinical symptoms by 69.03%, the effectiveness rate of self-rating anxiety scale by 17.2%, and the effectiveness rate of self-rating depression scale by 14.24%, thus improving the anxiety and depression and reducing the burden of clinical symptoms on patients.19 -22
Comprehensive treatment programs involving Chinese medicine have shown significant clinical benefits in rehabilitating psychological function after surgery for lung cancer. However, no standardized Chinese medical approach currently exists to specifically enhance the clinical advantages of psychological dysfunction rehabilitation after lung cancer surgery. Therefore, we focused on patients with anxiety and depression status after lung cancer surgery, and conducted a systematic review and meta-analysis of the use of traditional Chinese medicine for mental function rehabilitation after lung cancer surgery. This study aims to provide credible evidence for the clinical application of Chinese medicine in mental function rehabilitation after lung cancer surgery and in follow-up studies, and promote the development of expert consensus or clinical guidelines in this area.
Methods and Analysis
This study protocol was registered in PROSPERO with registration number “CRD42024532994.” It will be reported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. 23 Any changes during the review process will be documented appropriately.
Criteria for Including Studies
Types of studies
We will include only randomized controlled studies.
Types of participants
Patients who were diagnosed with lung cancer by histopathology, underwent radical surgical resection, and were diagnosed with depression or anxiety disorder, according to the Chinese Classification and Diagnostic Criteria for Mental Disorders Version 3 (CCMD-3) and the Diagnostic and Statistical Manual of Mental Disorders, United States.
Types of control groups
Control group will include patients who received conventional treatment, such as psychological counseling, non-pharmaceutical therapy, and others.
Types of interventions
The intervention group will receive combined TCM treatment based on the conventional treatment of the control group, including a Chinese medicine decoction and Chinese patent medicine.
Outcome measures
Primary outcomes: State of depression or anxiety (as indicated by the scale score).
(Secondary outcomes: Pulmonary function, QOL, postoperative complications, changes in laboratory test indicators in serum, and others.
Criteria for Excluding Studies
(1) Duplicate publications.
(2) For which original data cannot be obtained by contacting the original author.
(3) The language of publication was not English or Chinese.
Search Methods for the Identification of Studies
Data sources
We will search the relevant databases (PubMed, Cochrane Library, EMBASE, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure, Wanfang database, VIP database, and Chinese BioMedical Literature database) from their inception to April 22, 2024 (Figure 1).

Flow chart.
Searching strategies
The following terms will be used: “Lung Cancer OR Lung neoplasm OR Pulmonary neoplasms OR Neoplasms, Lung OR Neoplasms, Pulmonary OR Neoplasm, Pulmonary OR Pulmonary Neoplasm OR Cancer, Lung OR Cancers, Lung OR Lung Cancers OR Pulmonary Cancer OR Cancer, Pulmonary OR Cancers, Pulmonary OR Pulmonary Cancers OR Cancer of the Lung OR Cancer of Lung” and “Surgery” OR “Operation” OR “Postoperative OR Post Operation OR Postoperative Period OR After Operation OR After Surgery OR Post Operative OR Postoperatiue Period” and “Depression OR Depressive OR Depressive Disorder OR Mood Disorder OR Negative Emotion OR Negative Mood OR Anxiety OR Anxiety disorder OR Anxiety neurosis” and “Randomized controlled studies OR Randomized controlled studies OR Randomized controlled trial OR Randomized controlled trial OR Randomize control OR Randomize control OR Randomized OR Randomized OR Randomly,” the detailed searching strategies in PubMed was available in Table 1.
Searching Strategy in PubMed.
Data Collection and Analysis
Selection of studies
All data will be extracted independently by two investigators (LC and ZW), and any discrepancies between the reviewers will be resolved by an investigator (JL) until a consensus is reached.
Data extraction and management
We will search for studies published from the inception of each database to April 22, 2024. Data retrieved from the publications will include the first author name, publication year, country, intervention, comparison, intervention duration, study period, sample size, age at enrollment, sex, follow-up time, depression or anxiety score, QOL score, lung function, and serum detection indicators.
As some studies are ongoing or have not been published yet, new data may soon become available and, if included, may reduce the uncertainty of the results of the meta-analysis. Therefore, the Cochrane Collaboration recommends that meta-analysis articles be updated every 2 to 4 years after publication, as necessary.24 -26 Therefore, in the future, we will follow the update frequency requirements of the Cochrane Collaboration, update and screen the included articles every 2 to 4 years, and extract data for relevant data integration. The research team (at least three members) will then hold an online meeting to discuss the emerging data and explain its implications for the existing findings and conclusions. The main conclusions will be updated accordingly.
Data Synthesis
The results reported in the randomized controlled studies will be combined quantitatively. Meta-analysis will be performed using RevMan software. The selection of the model will depend on the results of the chi-squared and the I2 tests. For example, “P ≥ .1 and I2 ≤ 50%” indicates a lack of significant statistical heterogeneity, so a fixed effects model (FEM) will be used, otherwise a random effects model (REM) will be selected. If a meta-analysis is not appropriate owing to clinical/methodological issues or statistical heterogeneity, a narrative summary or relevant subgroup analysis will be used.
Measures of treatment effect
Relative risk (RR) will be selected to evaluate dichotomous outcomes with 95% confidence intervals (95% CI).
Assessment of publication bias
Funnel plots will be used to test the risk of publication bias if ≥10 studies are included.
Heterogeneity analysis
Heterogeneity analysis will be conducted using the chi-square test and I2. P ≥ .1 and I2 ≤ 50% indicate low heterogeneity and the statistics will be combined and analyzed using the FEM. P < .1 and/or I2 > 50% suggest a relatively large statistical heterogeneity among the included studies; if obvious clinical and methodological heterogeneity are excluded, the REM will be used for statistical analysis. The stability of the meta-analysis results will be tested using a sensitivity analysis. The source of heterogeneity should be analyzed and processed using a subgroup analysis or meta-regression. When there is high heterogeneity, a multi-level sensitivity analysis should be conducted to explore the stability of the results from the sources of heterogeneity. In addition, when heterogeneity is too obvious and cannot be resolved, meta-analysis will be performed with caution and conclusions will be drawn with caution.27,28
Subgroup analysis
Subgroup analyses will be performed to identify the factors that may be associated with clinical treatment efficacy for depressive anxiety after lung cancer surgery. We will conduct a subgroup analysis according to psychological state, surgical mode, pathological type, pathological stage, intervention duration, intervention measures, whether adjuvant therapy was performed, sex, age, and other factors.
Sensitivity analysis
Sensitivity analysis will exclude each study individually in the model to determine whether the heterogeneity changes significantly. If the combined effect before and after excluding a particular piece of literature does not change significantly, the results of the meta-analysis are relatively stable. If the exclusion of a particular piece of literature decreases heterogeneity, it may be the main source of heterogeneity. Further analysis is needed to find specific heterogeneity influencing factors by analyzing the differences between this study and other studies in the experimental protocol. Trials with low, unclear, and high risks of bias will be synthesized separately. The results of the sensitivity analysis will be reported.
Quality Assessment
Two reviewers will assess the quality of the randomized controlled studies using the Cochrane Risk of Bias Assessment Tool. The assessment of evidence quality in randomized controlled studies include the randomization, blinding, withdrawals, and dropouts.
Discussion
Anxiety and depression are prevalent psychological disorders in patients with cancer. Statistically, the prevalence of anxiety and depression in patients with lung cancer is 43.5% and 57.1%, respectively. Anxiety and depression account for 33.0% and 29.0% of patients with lung cancer, respectively. 29 Studies have found that patients with lung cancer often experience chronic stress after surgery, such as postoperative discomfort and follow-up treatment. Long-term pressure can lead to negative emotions such as anxiety and depression. Therefore, the rates of anxiety and depression after surgery are often higher than those before the surgery. Anxiety, depression, and other negative emotions can further weaken the immune system, stimulate malignant tumors growth and spread, and lead to unfavorable clinical results. 30 Therefore, in 2007, 10 the World Health Organization emphasized that psychosocial factors play an important role in tumor occurrence, development, and outcome and recommended that every patient be provided with effective tumor psychotherapy services. Effective psychological intervention is a key component of comprehensive rehabilitation treatment after lung cancer surgery and should be given attention. Currently, psychological rehabilitation methods for patients with lung cancer after surgery mainly consist of psychosocial and western medicine interventions. However, the application of these two interventions is often limited by a lack of professionals, low patient compliance, and drug side effects, which results in less than expected clinical efficacy. 31 Studies have found that TCM can significantly improve the negative emotions of anxiety and depression, enhance QOL, and prolong the survival of patients after lung cancer surgery.
Several studies have focused on the effect of mindfulness interventions on anxiety and depression in patients with NSCLC. 32 However, intervention methods are relatively limited, and very few specific analyses have focused on psychological rehabilitation after lung cancer surgery. At present, there is no systematic summary of the different TCM treatments for psychological rehabilitation after lung cancer surgery. In terms of research subjects, most studies have focused on anxiety and depression, while other psychological burdens such as stigma and guilt are frequently overlooked. Therefore, we will conduct a systematic review and meta-analysis to provide high-quality evidence supporting the effectiveness of TCM in enhancing psychological rehabilitation after lung cancer surgery. In this study, a systematic review and meta-analysis of the literature related to mental function rehabilitation after lung cancer surgery will be conducted to address the gap in the use of TCM in psychological rehabilitation after lung cancer surgery. This study is based on data from existing literature, which may exhibit some heterogeneity and bias. To obtain a high-quality evidence summary, we will standardize the literature retrieval and screening process as much as possible, and address potential biases through subgroup and sensitivity analyses.
However, the occurrence of limitations in the process of this study should be avoided: (1) The sample size of some studies may be small, and disease severity and course in patients may be inconsistent, so the extrapolation will be investigated; (2) some studies may not report the specific implementation method of the blind method, which may lead to a risk of bias; and (3) further exploration of the long-term efficacy of interventions is difficult owing to the short follow-up period of most trials. Therefore, large-sample, multicenter, and high-quality RCT studies should be carried out in the future to further observe the long-term efficacy and safety of TCM therapy on the mental function rehabilitation of patients after lung cancer surgery.
Footnotes
Author Contributions
(1) Conception and design: JL and LC. (2) Collection and assembly of data: LC and ZW. (3) Data analysis and interpretation: LC, GZ, YZ and XW. (4) Manuscript writing: LC, and ZW. (5) Final approval of manuscript: LC, ZW, XW, GZ, YZ and JL.
Data Availability
The data and materials are available from the corresponding authors upon request.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Key Research and Development Program of China (2023YFC3503300, 2023YFC3503301), High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023097).
Ethical Statement
All authors are accountable for all aspects of this work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study will be completed based on published literature; therefore, research ethics board approval and consent are waived.
Presenting and Reporting of Results
The PRISMA guideline will be used to support the reporting of the final full-text. The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.
Trial Registration
International Prospective Register of Systematic Reviews (PROSPERO): CRD42024532994.
