Postoperative outcomes in pulmonary nodule patients: a comparative analysis of aggressive vs. conservative management

Introduction

Lung cancer is a prevalent malignant neoplasm globally, characterized by the highest incidence and mortality rates. According to the global cancer statistics, lung cancer affects over 2 million new patients each year (1-3). Early-stage lung cancer is typically asymptomatic, leading to diagnoses at advanced stages for many patients and causing them to miss the optimal therapeutic window. This critical period is essential for effective treatment and significantly influences the prognosis and therapeutic strategies available. Improved living standards, the widespread adoption of low-dose computed tomography (LDCT) scans, and the push for early tumor diagnosis and treatment have significantly increased the early detection rates of pulmonary nodules (PNs), an early sign of lung cancer (4,5). However, this has also introduced new challenges, such as a high false-positive rate and postoperative anxiety (6).

In patients with PNs detected via LDCT scan, the majority present with small, low-density nodules, for which effective diagnostic approaches remain scarce. The majority of patients are diagnosed with indeterminate pulmonary nodules (IPN). For nodules with a higher risk of malignancy, diagnostic methods such as positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG), bronchoscopy, and percutaneous lung biopsies can be employed for definitive diagnosis, but these methods are significantly influenced by the location and nature of the nodules, leading to inconsistent diagnostic efficacy (7). Moreover, the economic burden of PET and the psychological resistance to bronchoscopy, along with the risk of complications from invasive methods, pose additional challenges in the diagnostic process (8). The vast majority of computed tomography (CT)-screened PNs are only recommended for CT follow-up, which may impact prognosis and lead to progression of lung cancer.

This dilemma is particularly significant in PNs of 5–10 mm, with pure ground-glass nodules and mixed ground-glass nodules being the most typical. There are some differences in the treatment methods and follow-up times for these two types of lung nodules across various clinical guidelines. For solitary pure ground-glass nodules over 5 mm, the National Comprehensive Cancer Network (NCCN) guideline and the American College of Chest Physicians (ACCP) guideline suggest four CT scans within 3 years (9,10). In contrast, the Fleischner Society Guidelines recommend initial CT scans every 3–6 months to check for lesion persistence (11). If stable or with a solid component under 6 mm, annual scans for 5 years are suggested. For multiple ground-glass nodules, long-term CT monitoring is also recommended. For ground-glass nodules with a diameter more than 6 mm, it is proposed that surgical resection should be taken if there is an increase in the solid component. Several guidelines recommend various forms of follow-up, yet there is no universal agreement on the best course of action due to insufficient large-scale, robust research to guide decision-making.

Given the potential malignant risk associated with IPN, strict follow-up plans are typically required in accordance with current clinical recommendations. During follow-up, patients may undergo multiple CT screening and experience significant psychological distress, such as anxiety or depression (12). A study has even considered psychological distress as a surgical indication for IPN (13). A recent study has found that impaired sleep quality is common among the patients with PNs (14). However, these studies have only focused on the preoperative psychological status and short-term psychological status after surgery of PN patients, neglecting their long-term postoperative psychological status. It is necessary to explore the impact of aggressive management and treatment on the postoperative psychological status of the patients with PNs.

This study aimed to compare the clinical characteristics, imaging characteristics and pathological diagnosis of PNs, the lung cancer diagnosis rates, accompanying symptoms at 3 months, and postoperative anxiety, depression, and sleep quality assessments at 3 years between patients who underwent aggressive management and those who had conservative management. This study will offer substantial guidance for treatment choices between aggressive and conservative management strategies. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-371/rc).

Methods

Participants

The observational study prospectively enrolled patients with PNs identified through CT scan in West China Hospital from January to December 2020 and retrospectively included patients who underwent surgical treatment following regular follow-up between 2013 and 2019. According to the time interval between diagnosis of PNs and surgical treatment, the patients were assigned to the aggressive management group and the conservative management group. The aggressive management group underwent surgery within one year of initial nodule detection by CT scan, while the conservative management group underwent surgery after more than one year of follow-up. All patients underwent video-assisted thoracic surgery (VATS) to remove PNs. The inclusion criteria were as follows: (I) diagnosed with small PN at initial CT detection (less than 10 mm in maximum diameter); (II) availability of CT images; and (III) known surgical pathological results. The exclusion criteria were: (I) incomplete clinical, pathological, or imaging data; and (II) lack of regular follow-up. All included patients had undergone surgery finally in West China Hospital of Sichuan University. Informed consent was obtained from all participants. The flowchart of patient selection is shown in Figure 1. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of West China Medical Center [2017(114)] and informed consent was obtained from all individual participants.

Figure 1 Flowchart of participant selection and grouping. CT, computed tomography.

Data collection

At the time of enrollment, demographic characteristics (gender, age, occupation status and contact information) and clinical characteristics (smoking history, personal history of disease, family history of cancer, and reasons for seeking medical treatment) were recorded through history taking. All data were collected through the 2020 Electronic Medical Records System and Siemens Medical Imaging System in West China Hospital.

The PNs were classified to benign or malignant according to the pathological diagnosis by biopsy or surgery, which served as the gold standard. According to the 2021 World Health Organization (WHO) Classification of Lung Tumors, lung cancer could be categorized into precursor lesion [including atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) (15). Clinical stage was based on the eighth edition tumor-node-metastasis (TNM) classification established in 2018 (16).

All CT examinations were performed with slice thicknesses of 1 mm. An experienced radiologist with over 5 years of clinical practice evaluated the CT scans and extracted image information. The data was subsequently reviewed by another senior radiologist with over one decade of expertise. Finally, two specialists independently interpreted the CT images and disagreements were discussed to reach consensus. CT images after the diagnosis of PNs were used as baseline features. The radiological features of PNs on initial and preoperative CT scans were evaluated, consisting of the timepoint, nodule diameter, nodule location, nodule density, and the number of PNs. In addition, we also documented that if the PNs grew, stayed the same size or got smaller. Details about the key metrics were as follows: (I) nodule diameter, recorded at the maximum measured in the lung window setting; (II) nodule location, categorized as upper lobe, non-upper lobe, right lung, or left lung; (III) nodule density, classified as solid or ground-glass (including pure ground-glass nodule and mixed ground-glass nodule). Enlargement was defined as an increase in size exceeding 1.5 mm or a rise in density, whereas reduction entailed a decrease in size by more than 1.5 mm or a decline in density.

The symptoms of patients (including cough, pain, and shortness of breath) were recorded 3 months after surgery. We used the MD Anderson Symptom Inventory (MDASI) to evaluate the patients’ symptoms, which was developed by the University of Texas MD Anderson Cancer Center in the United States in 2000 (17). The MDASI consists of 13 symptom items and 6 interference items. Each item is scored between 0 (not at all) and 10 (as bad as you can imagine). Besides, the Chinese version of this questionnaire has been proven to be valid, reliable and sensitive to measure the symptom severity in cancer patients (18).

The survival status (survival or death) and the quality-of-life indicators (anxiety, depression, and sleep disorders) were assessed 3 years after surgery. In terms of death, the time and cause of death were documented. Anxiety was evaluated using the Generalized Anxiety Disorder 7-item (GAD-7) scale, and depression was assessed using the Patient Health Questionnaire 7-item (PHQ-7) scale (19-21). Both scales comprise seven items, rated on a scale from 0 to 3, culminating in a maximum score of 21. Anxiety and depression levels were categorized as follows: no anxiety or depression (0–6 points), mild (7–10 points), moderate (11–13 points), and severe (14–21 points). Sleep disorders were assessed using the Athens Insomnia Scale (AIS-8), which includes eight questions scored from 0 to 3 points, with a total score of 24 points (22). Patients scoring more than 6 points on the scale are considered to have a sleep disorder. Follow-up data were primarily collected through telephone interviews, supplemented by medical records.

Statistical analysis

Propensity score matching was performed at a ratio of 1:2 based on age, gender, smoking and family history of tumors. The Shapiro-Wilk test was performed to check the normality of data. Continuous variables were described as mean and standard deviation (SD), with the independent samples t-test used to assess variations between the groups. Categorical variables were reported as number and percentage and compared using the chi-square test. The Fisher’s exact test was used to analyze data with a frequency less than 5. We employed multivariable logistic regression to examine the association between treatment groups and 3-month symptoms, as well as 3-year quality-of-life indicators. In model 1, any confounding factors were not adjusted for, as age and gender were adjusted for in model 2. Model 3 adjusted for age, gender, smoking and postoperative pathological diagnosis. Subgroup analysis was performed to explore if the association differed for subgroups classified using different parameters including age, gender, smoking and postoperative pathological diagnosis. Statistical significance was based on two-tailed P values, with a value of P<0.05 being statistically significant. All data analysis was conducted using R (Version 4.3.2) software.

Results

Patients and baseline characteristics

In this observational study, a total of 3,074 patients due to PNs resection were collected in 2020, and 190 patients that initially met the inclusion criteria from 2013 to 2019 were screened. Following the application of inclusion and exclusion criteria, the data of 604 patients were considered valid. After the propensity score matching, the final cohort comprised 396 patients, consisting of 109 males and 287 females. The clinical characteristics of the patients in the aggressive management group and conservative management group were shown in Table 1. The aggressive management group was shown to have a younger mean age (53.3 vs. 57.2 years, P=0.001) compared with the conservative management group. Additionally, the conservative management group had a notably higher proportion of smokers (19% vs. 9.5%, P=0.007). Conversely, the conservative management group showed a higher incidence of prior tumor history (29% vs. 8.3%, P=0.001). Regarding the imaging characteristics of the patients, the proportion of patients showing PNs enlargement during the preoperative observation period was significantly higher in the conservative management group than in the aggressive management group (76% vs. 3.4%). There was no statistically significant difference in the initial size of PNs between the radical group and the conservative group. However, the preoperative nodule size of the conservative management group was significantly higher than the aggressive management group (12.30 vs. 7.41 mm, P=0.001). These findings underscored the distinct clinical profiles between the two groups. However, no significant disparities in gender, the family history of lung cancer, the family, history of other tumors number of PNs or the location of PNs were observed between the two groups.

Diagnosis of patients with lung cancer

The results of pathological types after the PNs resection were shown in Table 2. A total of 333 patients were confirmed cases of lung cancer, including adenocarcinoma, squamous cell carcinoma and other non-small cell carcinomas, with 215 (81.4%) in the aggressive management group and 118 (89.4%) in the conservative management group. In the aggressive management group, 214 cases (81.1%) were adenocarcinomas, compared to 117 cases (88.6%) in the conservative management group. Regarding pathological classification of adenocarcinoma, the incidence of IA type within the aggressive management group was markedly reduced compared to the conservative management group [25 (9.5%) vs. 35 (27%)], whereas the proportion of MIA type was significantly higher [183 (69%) vs. 68 (52%)]. In the aggressive management group, there was 1 case (0.3%) of squamous cell carcinoma. In the conservative management group, there were 1 case (0.8%) of other non-small cell lung cancers. Notably, the aggressive management group exhibited higher rates of precursor lesions (3.8% vs. 2.3%) and benign nodules (15% vs. 8.3%) compared with the conservative management group.

The pathological staging results of patients diagnosed with lung cancer were shown in Table 3. Regarding pathological staging, the majority of patients with lung cancer in the aggressive management group (97%) were in stage IA, which was significantly higher than the conservative management group (92%). Alternatively, the ratio of stage IB and after in the conservative management group surpassed that in the aggressive management group. These differences were statistically significant (P<0.05). However, no significant disparity in the diagnosis of multiple nodules was observed between the aggressive management group and the conservative management group (P=0.73).

Follow-up outcomes

As shown in Table 4, postoperative cough for the 3-month postoperative follow-up of aggressive management group was noted in 122 patients (46%), pain in 105 (40%), and shortness of breath in 81 (31%). In contrast, within the conservative management group, postoperative cough was documented in 27 patients (20%), pain in 31 patients (23%), and shortness of breath in 25 patients (19%). The incidence of symptoms such as cough, pain, and shortness of breath was notably higher in the aggressive management group, and the comparison of symptoms between the two groups at 3 months after surgery was statistically significant (P<0.05).

In the 3-year postoperative assessment of anxiety, depression, and sleep disorders. Notably, no patient deaths occurred during the follow-up period of this study. The conservative management group demonstrated a significantly higher proportion of patients with anxiety and depression symptoms compared to the aggressive management group (5.3% vs. 0.8%, P=0.008). However, there was no significant difference between the two groups in terms of sleep disorders (P=0.40).

Through univariate and multivariate logistic regression analyses, we identified that the choice of conservative and aggressive management was associated with postoperative cough, pain, shortness of breath (P<0.05, Table 5). Aggressive management is a risk factor for cough [odds ratio (OR) =3.34; 95% confidence interval (CI): 2.08–5.52; P=0.001], pain (OR =2.15; 95% CI: 1.35–3.49; P=0.001), and shortness of breath (OR =1.89; 95% CI: 1.15–3.20; P=0.01). At the same time, aggressive management is a protective factor for anxiety and depression (OR =0.14; 95% CI: 0.02–0.57; P=0.01). However, we did not find a significant correlation between the treatment groups and sleep disorder (P=0.43).

Subgroup analysis results are shown in Figure 2. Female is independently related to pain at 3 months postoperatively. Non-smoking status showed a significant association with cough. Pathological diagnosis of malignancy showed significant association with cough, pain, and shortness of breath. However, no interaction effects were observed between treatment groups and accompanying symptoms and sleep disorder.

Figure 2 Subgroup analysis results of cough, pain, shortness of breath and sleep disorder. (A) Subgroup analysis results of cough. (B) Subgroup analysis results of pain. (C) Subgroup analysis results of shortness of breath. (D) Subgroup analysis results of sleep disorder. CI, confidence interval; OR, odds ratio.

Discussion

The decision of aggressive management and conservative management of incidental PNs is a significant topic of global interest (23). In our study, we prospectively enrolled patients and divided them into two groups: the aggressive management group and the conservative management group. We compared various outcomes after the surgery, including the rates, pathological types and pathological stages of lung cancer diagnosis, the occurrence of postoperative symptoms within 3 months, and assessments of anxiety, depression, and sleep quality observed 3 years after surgery between the two groups. We also employed propensity score-matched analysis and multivariable logistic regression to examine the associations between treatment groups and 3-month symptoms, as well as 3-year quality-of-life indicators. Our findings indicated that the aggressive management group had a higher incidence of precursor and benign lesions, as well as a greater proportion of MIA type. However, this group also experienced a higher possibility of postoperative symptoms such as cough, pain, and shortness of breath. Female patients are more likely to experience coughing and shortness of breath due to aggressive management, while male patients are more prone to sleep disorders as a result of aggressive management. In contrast, patients in the conservative management group, who underwent long-term follow-up, were more likely to have psychological symptoms, including anxiety and depression.

It is found that patients who underwent aggressive management for PNs experienced a shorter time interval from detection to surgical intervention, with the nodules measuring a smaller average diameter of 6.671 mm. The aggressive management group also received earlier pathological classification and staging compared to those in the conservative management group, potentially improving the detection rate of early-stage lung cancer. A study on incidental surgery for PNs has indicated that the postoperative benign rate is higher in patients who underwent aggressive treatment (20.2% vs. 4%) (24). In contrast, the control group, which underwent surgery after observing a persistent increase in nodule size through prolonged regular follow-up, demonstrated a higher proportion of lung cancer diagnoses and greater accuracy in lung cancer detection compared to the aggressive treatment group, mitigating the risks of overtreatment.

However, the pathological results from the conservative management group revealed that, in comparison to the aggressive treatment group, a higher proportion of lung cancer diagnoses after long-term follow-up were of IA type. In these patients, IA type tumor cells had already infiltrated surrounding normal tissues and may have invaded lymphatic and vascular structures, which could increase the risk of lymph node metastasis or distant spread and lead to poorer prognostic outcomes (25). Additionally, research on the survival rates of stage I lung cancer indicates that the 5-year survival rates decreased with the progression of stage (26). The majority of patients in the aggressive management group were classified as IA1, while those with relatively later stages of lung cancer constituted a smaller percentage compared to the conservative management group, thereby predicting a higher survival rate. Taking into account the specific risks associated with PNs and the patients’ preferences, an increased inclination towards aggressive treatment may prove more beneficial for patient prognosis.

There have been many studies on the accompanying symptoms after surgery, but study on the effect of surgery timing on the accompanying symptoms is insufficient. In our study, the postoperative symptoms of the conservative management group were milder than those of the aggressive management group. With a longer follow-up and a higher incidence of tumor history, chronic obstructive pulmonary disease (COPD), and asthma, conservatively managed patients were more likely to choose follow-up, cultivating better psychological adaptability and reducing post-surgical stress like coughing and shortness of breath. Due to the presence of existing diseases, the conservative management group patients more inclined to choose follow-up observation, thus establishing better psychological adaptability in the long-term follow-up observation process, which can alleviate the stress reactions such as cough, chest tightness, and shortness of breath that occur after surgery (24). Notably, the conservative management group had a lower chance of experiencing postoperative accompanying symptoms, leading to benefits for psychological health (27). Our subgroup analysis found that aggressive treatment is a risk factor for cough, pain and shortness of breath in the population with malignant tumors. In clinical practice, we should take measures for patients with malignant tumors to alleviate these postoperative accompanying symptoms. Due to the limitations of the retrospective study, we did not collect data on postoperative complications. The situation regarding postoperative complications can be referred to the previous research of West China Hospital of Sichuan University (28,29).

Current guidelines often rely on nodule type and size to determine surgery, sometimes overlooking the psychological effects of timing on patients. The Fleischner Society advises over 5 years of monitoring for stable small PNs, while Asian consensus guidelines propose extended surveillance. The Clinical Practice Consensus Guidelines for Asia propose annual scans for 3 years if the nodule remains stable, followed by yearly scans. In the vast majority of cases, various guidelines prioritize follow-up over surgical resection for PNs. Despite the indolent nature of most PNs, the watchful waiting approach can provoke significant cancer anxiety in patients. Though most PNs are benign and many grow slowly, advanced lung cancers can stem from them. The “watchful waiting” approach may cast a shadow of “cancer anxiety” over patients, heightening psychological stress and potentially causing anxiety and depression.

A lot of current guidelines often take nodule type and size as key indicators for surgery, often neglecting the psychological effects of the timing of surgery on patients. The Fleischner Society Guidelines recommend a follow-up duration of over 5 years for stable PNs, while the Clinical Practice Consensus Guidelines for Asia suggest even longer periods. Despite the majority of nodules are benign and numerous PNs grow slowly, advanced-stage lung cancers stem from these nodules. This “watchful waiting” strategy can put patients under the shadow of “cancer anxiety”, increasing their psychological burden and leading to anxiety and depression (30). Research indicates that approximately 60.4% of lung nodule patients worry monthly, 17.8% daily, and 59.3% experience anxiety (31). In our study, the aggressive management group underwent surgery shortly after nodule detection, determining the pathological nature and allowing for early-stage lung cancer diagnosis. Follow-up calls revealed fewer anxiety and depression symptoms in this group compared to the conservative management group, which might explain the preference for aggressive management among many patients. Although not conclusively proven, severe anxiety or depression has been proposed as a potential indication for surgery in PNs management expert consensus, suggesting that psychological distress should be scored and considered as a surgical indication for PNs (13). We believe that along with considering factors causing follow-up anxiety, one should also account for factors affecting postoperative anxiety and depression, such as potential complications and the psychological impact of a lung cancer diagnosis. Our research findings are also in line with this theory. In the results of the logistic regression, aggressive treatment was regarded as a protective factor against 3-year postoperative anxiety and depression. In other words, early surgery for PN patients who meet surgical criteria may benefit their psychological. Sleep disturbance is common among PN patients (44.9%), with the elderly and women more susceptible (14). However, our subgroup analysis revealed that aggressive treatment was a risk factor for sleep disorders in male patients. But no matter what, both the mental symptoms and sleep conditions of patients need to be comprehensively considered.

Distinguishing between benign and malignant PNs is a complex clinical challenge and a significant source of patient anxiety. International guidelines advocate for strict surveillance programs to actively monitor these nodules, thereby preventing overdiagnosis and overtreatment. While aggressive management can lead to early lung cancer detection and extended survival, it also carries the risk of unpredictable physical impairments and complications (32). We believe that the purpose of regular follow-ups is to identify the most appropriate timing for intervention.

Accurately assessing the risk based on nodule size and density remains challenging, but various methods can aid in surgical decision-making. Regular monitoring can promptly detect high-risk nodules. Integrating demographic characteristics, imaging information, and follow-up data into diagnostic models powered by artificial intelligence can help assess the risk level of PNs and guide the selection of treatment timing (33). Technological advancements have shifted from unidimensional to multidimensional diagnostic systems, which can reduce unnecessary invasive procedures for low-risk cases and ensure timely intervention for very high-risk nodules, preventing diagnostic delays.

There are already many studies on the psychological state after PN resection, but to our knowledge, this represents the first 3-year longitudinal follow-up study examining the psychological state after PN resection. While subgroup analysis offers the advantage of exploring treatment effects across different populations, our study is not without limitations. However, these limitations should be acknowledged. Firstly, our study did not evaluate the preoperative psychological status and postoperative symptoms of the patients because of the limitation of retrospective study. Secondly, the relatively small sample size precluded the possibility of conducting robust subgroup analyses, particularly for anxiety and depression. Third, this was a single-center study, with participants recruited exclusively from West China Hospital, China. Future studies should aim to incorporate larger sample sizes from diverse regions. Despite these limitations, our findings provide valuable insights into the long-term psychological impact of this procedure.

As living standards improve, there is heightened awareness of early cancer prevention and treatment. However, the lack of disease knowledge and fear of missing the best treatment window can lead to or promote aggressive management choices. It is essential to consider factors contributing to surveillance anxiety, including underlying diseases, cancer history, treatment experiences, education level, economic status, family and social support, and psychological state, when advocating for follow-ups. Personalized treatment plans should be provided based on individual differences.

Conclusions

Aggressive management can significantly reduce the incidence of IA type and rise the early detection rate of lung cancer, particularly for stage IA. However, it may also lead to more postoperative symptoms such as cough, pain, and shortness of breath, potentially leading to unnecessary medical interventions. Despite these drawbacks, aggressive management may positively impact the reduction of postoperative anxiety and depression in patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-371/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-371/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-371/prf

Funding: This work was supported by grants from National Natural Science Foundation of China (No. 32201231 to L.L.). The funding sources were not involved in study design; collection, analysis, and interpretation of data; or writing of the manuscript.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-371/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of West China Medical Center [2017(114)] and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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