Psychological distress in patients with detected pulmonary nodules from lung cancer screening

Introduction

Background

Lung cancer remains one of the leading causes of cancer-related mortality globally (1,2). The implementation of low-dose computed tomography (LDCT) screening has resulted in earlier detection of pulmonary nodules (PNs) (3,4). PNs are defined as discrete, rounded opacities measuring ≤3 cm in diameter within the lung parenchyma (5). Based on radiologic appearance, PNs can be classified as solid, part-solid (subsolid), or pure ground-glass nodules (5).

As many PNs have been found to be benign (6), clinical surveillance is frequently recommended based on the level of imaging indicators (5). For suspicious PNs for malignant potential, a surgical biopsy/resection is recommended (7). In routine clinical practice, patients with newly detected PNs during health screening are evaluated holistically, considering both radiologic features and clinical context. Empirical short-term antibiotic therapy may be considered when an infectious or inflammatory etiology is suspected and no other concerning abnormalities are identified, followed by repeat LDCT to assess lesion resolution. If the nodule shrinks, fades, or disappears, it is typically regarded as benign, avoiding invasive procedures and reducing the risk of overtreatment (5,6). Conversely, if the lesion persists or grows, a more aggressive approach such as biopsy or resection may be pursued, particularly when malignancy is suspected (7). If no significant change is observed on follow-up LDCT, further management, such as surgical biopsy/resection or continued radiological surveillance, is typically determined based on nodule size, growth rate, morphology, and malignancy risk assessment.

Provider recommendations based on the screening outcomes may be associated with psychological distress (8,9), demonstrated by anxiety and depression rates of 42.4% and 26.4%, respectively (10). Insomnia is also common, reported in nearly half of patients studied with anxiety [odds ratio (OR) =1.78] and depression (OR =1.84), identified as independent risk factors for impaired sleep (11). Patients with indeterminate PNs on screening under surveillance experience significantly higher odds of lung cancer-related anxiety (OR =3.96, P<0.001), dejection (OR =1.35, P=0.015), and existential thoughts (OR =1.30, P=0.018), compared to individuals with negative findings on screening (12). The uncertainty of patients on surveillance, even though medically classified as low risk, has also been associated with psychological distress in other cancer contexts, such as in patients undergoing active surveillance for early-stage prostate cancer (13,14).

In men and women who undergo lung cancer screening, women are reported to have higher rates of anxiety (21.57% vs. 12.31%) and depression (18.05% vs. 9.30%) compared with men (P<0.05) (9). In addition, physical symptoms such as chest pain, acid reflux, and abnormal throat sensations were also reported and associated with increased psychological distress (15). Psychological distress can influence decision-making, evidenced by one study that reported anxious patients more likely to desire surgical intervention to determine the nature of the PNs, which often are benign (9).

Rationale and knowledge gap

Psychological distress has been frequently reported after detection of PNs by LDCT (8). However, existing studies mainly report symptom prevalence using cross-sectional designs, and rarely evaluate longitudinal psychological changes or compare outcomes between surgical resection and radiological surveillance (10,12). The psychological impact of resolving diagnostic uncertainty through surgery vs. continued observation remains unclear. Moreover, little is known about which patient subgroups are most vulnerable to persistent distress, limiting the ability to deliver targeted support (9). Addressing these gaps is essential to inform patient-centered PN management and integrate psychological care into lung cancer screening pathways.

Objective

We hypothesized that persistent diagnostic uncertainty may be associated with sustained distress and that psychological trajectories may differ between patients managed surgically and those managed with radiological surveillance. Therefore, this study addresses the gap in knowledge of psychological distress associated with lung cancer screening for those on surveillance vs. those who undergo a surgical biopsy/resection of PNs. We present this article in accordance with the STROBE reporting checklist (16) (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1153/rc).

Methods

Study design and participants

This prospective single-center study was conducted at the Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, from June to December 2024. The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. 2021-190; date: 31 December 2021) and adhered to the Declaration of Helsinki and its subsequent amendments (17). Written informed consent was obtained from all participants prior to enrollment. Psychological assessments were administered at outpatient visits using structured questionnaires.

Inclusion criteria were: (I) were aged ≥18 years; (II) had newly detected PNs (diameter ≤3 cm) confirmed by LDCT; (III) were able to complete the questionnaire independently; and (IV) provided informed consent. Exclusion criteria included: (I) known psychiatric disorders; and (II) prior thoracic surgery.

All participants were recruited using a consecutive enrollment strategy at a thoracic surgery clinic, underwent baseline psychological assessments, and were subsequently categorized into two groups based on clinical management: a surgical group, consisting of patients who received surgical biopsy or resection; and a surveillance group, comprising patients managed conservatively with serial LDCT monitoring. The 1-month follow-up assessment was defined a priori as 1 month after the initial clinical management decision, corresponding to 1 month after surgical intervention in the surgical group, and to a comparable time point after baseline evaluation in the surveillance group.

Psychological measures and clinical data

Baseline demographic and clinical characteristics were collected from medical records and structured intake forms, including: age, gender, smoking history, prior cancer history, family history of malignancy, number of nodules (solitary vs. multiple), nodule size (≤10, 11–20, 21–30, >30 mm), and radiologic features [pure ground-glass opacity (GGO), mixed GGO, or solid appearance]. Psychological status was assessed using three standardized and validated self-report instruments (Table S1). Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report tool evaluating anxiety severity over the past 2 weeks. Total scores range from 0 to 21. Severity levels were defined as: 0–4 (minimal), 5–9 (mild), 10–14 (moderate), and 15–21 (severe). A score ≥10 was used to indicate clinically significant anxiety (Cronbach’s α=0.89) (18). Patient Health Questionnaire-9 (PHQ-9) is a 9-item tool assessing depressive symptoms. Total scores range from 0 to 27, categorized as: 0–4 (minimal), 5–9 (mild), 10–14 (moderate), 15–19 (moderately severe), and 20–27 (severe). A score ≥10 was used to define clinically significant depression (Cronbach’s α=0.86–0.89) (19). Insomnia Severity Index (ISI) is a 7-item scale for evaluating insomnia severity. Total scores range from 0 to 28: 0–7 (no insomnia), 8–14 (subthreshold), 15–21 (moderate), and 22–28 (severe). Insomnia was defined as ISI ≥8 (Cronbach’s α=0.83) (20).

Each instrument was administered at baseline and again at 1-month follow-up. For longitudinal comparisons, GAD-7 and ISI were converted into ordinal severity levels based on validated thresholds: 0, minimal or none; 1, mild; 2, moderate; and 3, severe. For depression (PHQ-9), five levels [0–4] were used to reflect its standard classification. Changes in symptom severity were categorized as follows: “improved”, decrease by ≥1 grade; “worsened”, increase by ≥1 grade; “stable”, no change in grade. Changes in psychological symptom severity were assessed using both categorical and continuous approaches.

Outcomes

Primary outcome was psychological symptom improvement at 1-month follow-up, defined as a reduction in anxiety, depression, or insomnia severity levels compared to baseline. Secondary outcomes included the identification of clinical predictors associated with symptom improvement and the distribution of symptom trajectories (improvement, stability, or worsening) across subgroups.

Statistical analysis

Descriptive statistics were used to summarize baseline demographic, clinical, and psychological characteristics. Categorical variables were presented as frequencies and percentages, and continuous variables as means with standard deviations (SDs) or medians with interquartile ranges (IQRs), as appropriate. Group comparisons were performed using the chi-square test or Fisher’s exact test for categorical variables. For ordinal variables with paired observations, such as changes in GAD-7, PHQ-9, and ISI severity categories over time, the Wilcoxon signed-rank test was used to assess within-subject differences between baseline and follow-up. Sankey diagrams were applied to depict categorical transitions between two predefined time points, illustrating individual-level changes across severity states. In this study, changes in severity categories for anxiety, depression, and insomnia were tracked using Sankey diagrams to visualize individual transitions (improvement, stability, or worsening) from baseline to 1-month follow-up. Subgroup stratification was further explored using heatmaps according to variables such as age group, gender, and imaging characteristics.

To evaluate longitudinal changes in psychological symptoms using continuous scale scores, a repeated-measures multivariate analysis of variance (MANOVA) was performed. Treatment group (surgical resection vs. radiological surveillance) was specified as a between-subject factor, time (baseline and 1-month follow-up) as a within-subject factor, and psychological measure (GAD-7, PHQ-9, and ISI) as the multivariate outcome.

Binary logistic regression models were constructed to identify predictors of psychological improvement, defined as a reduction in severity levels of anxiety, depression, or insomnia from baseline to 1-month follow-up. Results were reported as ORs with corresponding 95% confidence intervals (CIs). The models included demographic factors (age, gender), behavioral characteristics (smoking history), clinical background (personal or family history of malignancy), and nodule features (number, size, and radiologic type).

To further control for baseline confounding and approximate the conditions of a randomized controlled trial, inverse probability of treatment weighting (IPTW) based on propensity scores was applied. Propensity scores were estimated using a logistic regression model including baseline demographic (age, gender), psychological (GAD-7, PHQ-9, ISI grade), behavioral (smoking history), clinical (personal and family history of malignancy), and radiologic features (nodule number, size, and imaging type). Stabilized weights were calculated and applied to generate a weighted pseudo-population in which covariates were balanced across surgical and non-surgical groups. Standardized mean differences (SMDs) were used to assess covariate balance before and after weighting. Weighted binary logistic regression models were fitted to evaluate the effect of surgery on psychological improvement (anxiety, depression, and insomnia), with results reported as ORs and 95% CIs.

All statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA) and R software version 4.2.1. A two-sided P<0.05 was considered statistically significant.

Results

Baseline psychological distress and clinical characteristics

After applying the exclusion criteria, 936 (83.1%) of 1126 patients with PNs were included in the longitudinal observational cohort (Figure 1). Among 936 patients with newly detected PNs, 40.2% reported clinically significant anxiety, 31.7% depression, and 24.6% insomnia. The majority were aged 35–59 years (53.6%) and female (63.2%) (Figure 2).

Figure 1 Flowchart of the study design. PN, pulmonary nodule.

Figure 2 Baseline psychological distress in patients with PNs. (A) Anxiety; (B) depression; (C) insomnia. GGO, ground-glass opacity; PN, pulmonary nodule.

Psychological distress varied significantly by age and gender. Patients <35 years exhibited the highest rates of anxiety (50.4%) and depression (39.5%), while those ≥60 years reported the lowest (anxiety: 28.9%; depression: 27.2%) (P<0.001 and P=0.04, respectively). Insomnia showed no significant age association but was slightly more prevalent in younger patients (<35 years: 27.1%, P=0.406). Female patients consistently exhibited higher rates of anxiety (46.3% vs. 29.7%), depression (36.0% vs. 24.4%), and insomnia (30.1% vs. 15.1%) compared to males (all P<0.001) (Table 1).

While smoking and cancer history were not significantly associated with psychological symptoms, a family history of malignancy was marginally linked to higher anxiety (P=0.06). Nodule characteristics revealed additional patterns: nodules ≤10 mm were associated with higher anxiety (45.5%, P=0.001), nodules 11–20 mm with slightly elevated insomnia (28.7%, P=0.10), and mixed GGO lesions were linked to higher depression rates (39.6%, P=0.03) (Table 1).

In summary, younger age, female, and ambiguous imaging features such as mixed GGO were key correlates of elevated baseline psychological distress in patients undergoing LDCT screening.

Longitudinal changes in psychological status

All participants were followed up at a fixed interval of 1 month after baseline assessment. Among the 936 patients, including 472 who underwent surgical resection and 464 under surveillance, overall psychological status improved significantly in the surgical group. Wilcoxon signed-rank test revealed a significant reduction in anxiety (Z=−3.692, P<0.001), depression (Z=−2.985, P=0.003), and insomnia grades (Z=−4.647, P<0.001) at 1-month follow-up compared to baseline. Specifically, 14.9% showed anxiety improvement, 10.9% depression improvement, and 10.5% insomnia improvement, while most patients remained stable (Figure 3).

Figure 3 Changes in psychological symptoms from baseline to 1-month follow-up in patients with PNs. (A-C) Sankey diagrams illustrating individua trajectories of (A) anxiety, (B) depression, and (C) insomnia between baseline and 1-month follow-up. (D-F) Heatmaps showing subgroup-specific changes in (D) anxiety, (E) depression, and (F) insomnia. G, grade; GGO, ground-glass opacity; PN, pulmonary nodule.

Across all three psychological domains, symptom changes were influenced by age, gender, smoking status, nodule size, and imaging features, with patterns showing both consistency and domain-specific differences (Figure 3). Patients aged 35–59 years consistently demonstrated the greatest improvement—18.9% in anxiety, 13.5% in depression, and 13.1% in insomnia, while the majority of those ≥60 years remained stable (anxiety: 89.2%; depression: 89.5%; insomnia: 90.5%; P≤0.01). Female patients showed greater variability than males, with higher rates of both improvement (anxiety: 19.8% vs. 6.4%; depression: 14.0% vs. 5.5%; insomnia: 14.5% vs. 3.5%) and worsening (anxiety: 12.7% vs. 3.8%; depression: 10.8% vs. 2.6%; insomnia: 6.4% vs. 1.2%) compared with males (all P<0.001) (Tables 2-4). Non-smokers generally fared better than smokers, with improvement rates of 16.5% vs. 6.5% for anxiety (P=0.001), 11.6% vs. 7.1% for depression (P=0.01), and 12.0% vs. 2.6% for insomnia (P<0.001). Nodule characteristics also shaped symptom changes: patients with ≤10 mm nodules showed greater fluctuations in anxiety severity (P<0.001), while those with 11–20 mm nodules achieved the highest improvement rates for depression (12.5%, P<0.001) and insomnia (13.6%, P=0.02). Mixed GGO lesions were associated with the highest improvement in anxiety (17.7%, P=0.02) and insomnia (15.6%, P=0.002), as well as favorable depression improvement rates, while variability in outcomes was also observed within this subgroup (Tables 2-4).

Longitudinal comparison of psychological scores between surgical and surveillance groups

Baseline demographic, clinical, radiologic, and psychological characteristics stratified by treatment strategy are summarized in Table 5. Patients in the surgical group were significantly older than those in the surveillance group (P=0.001). Differences were also observed in family history of malignancy, which was more frequent in the surveillance group (P=0.040). Marked differences in nodule-related characteristics were noted between groups. Patients undergoing surgery more commonly presented with larger nodules, whereas nodules ≤10 mm were more prevalent in the surveillance group (P<0.001). Imaging features also differed significantly, with a higher proportion of mixed GGO in the surgical group (P<0.001).

With respect to baseline psychological status, the distribution of anxiety (GAD-7) and insomnia (ISI) severity differed modestly between groups (P=0.03 and P=0.001, respectively), while baseline depression severity (PHQ-9) was comparable between the surgical and surveillance groups (P=0.19). No significant between-group differences were observed for gender, smoking history, prior cancer history, or PNs number.

Mean psychological symptom scores with corresponding 95% CIs at baseline and 1-month follow-up, stratified by treatment strategy, are shown in Figure 4. Over the 1-month follow-up period, patients managed with surgical resection demonstrated consistent reductions in mean symptom scores across all three psychological domains. The mean change (follow-up minus baseline) was −1.50 (95% CI: −1.73 to −1.28) for GAD-7, −0.87 (95% CI: −1.10 to −0.65) for PHQ-9, and −0.85 (95% CI: −1.12 to −0.58) for ISI. In contrast, patients undergoing radiological surveillance showed modest increases or minimal changes in symptom scores, with mean changes of +0.60 (95% CI: 0.43 to 0.78) for GAD-7, +0.30 (95% CI: 0.13 to 0.48) for PHQ-9, and +0.22 (95% CI: 0.03 to 0.41) for ISI.

Figure 4 Longitudinal trajectories of psychological symptom scores by treatment strategy. CI, confidence interval; GAD-7, Generalized Anxiety Disorder-7; ISI, Insomnia Severity Index; PHQ-9, Patient Health Questionnaire-9.

To further examine whether longitudinal changes in psychological symptoms differed by management strategy, a repeated-measures MANOVA was performed using continuous GAD-7, PHQ-9, and ISI scores. A significant main effect of time was observed for anxiety, depression, and insomnia (all P<0.001), indicating overall changes in psychological symptoms from baseline to follow-up across the study population. Importantly, significant time-by-treatment group interactions were identified for all three psychological outcomes (anxiety: F=210.762, P<0.001; depression: F=65.631, P<0.001; insomnia: F=40.302, P<0.001), demonstrating distinct longitudinal trajectories between the surgical and surveillance groups. Descriptive statistics further illustrated that patients undergoing surgical resection experienced greater reductions in psychological symptom scores at 1-month follow-up compared with those managed by surveillance alone.

Predictors of psychological symptom improvement

Binary logistic regression was used to identify independent predictors of psychological symptom improvement (improved vs. non-improved) at 1-month follow-up.

Surgical intervention emerged as the most powerful predictor of improvement across all three psychological domains. In unadjusted analyses, surgery was associated with markedly higher odds of improvement in anxiety (OR =77.88, 95% CI: 7.48–810.37, P=0.004), depression (OR =9.91, 95% CI: 5.22–18.82, P<0.001), and insomnia (OR =11.56, 95% CI: 5.78–23.13, P<0.001) (Figure 5).

Figure 5 Forest plot of predictors for persistent anxiety, depression, and insomnia. (A) Anxiety; (B) depression; (C) insomnia. CI, confidence interval; GGO, ground-glass opacity; OR, odds ratio; PN, pulmonary nodule.

Demographic factors were consistently associated with symptom improvement. Compared with patients aged ≥60 years, those aged 35–59 years were more likely to experience improvement across all domains, including anxiety (OR =3.43, P<0.001), depression (OR =2.51, P=0.001), and insomnia (OR =2.17, P=0.007). Patients younger than 35 years also showed a higher likelihood of anxiety improvement (OR =2.15, P=0.045). Female sex was similarly associated with a greater probability of improvement in anxiety (OR =3.79, P<0.001), depression (OR =3.32, P=0.001), and insomnia (OR =3.77, P<0.001).

Nodule characteristics showed domain-specific effects. Compared with larger lesions, small nodules (≤10 mm) were associated with a higher likelihood of anxiety improvement (OR =3.07, P=0.040). Similarly, mixed GGO lesions were associated with an increased probability of improvement in depressive symptoms (OR =2.17, P=0.004). Other variables, including smoking status and prior cancer history, were not significant predictors of improvement in any psychological domain. Collectively, these findings highlight that demographic factors (female and age <60 years), specific nodule features (small size or mixed GGO), and clinical pathway (surgery vs. surveillance) are critical determinants of psychological outcomes. Surgical intervention was associated with substantially lower odds of persistent psychological distress across all three domains.

IPTW-adjusted analysis of surgery on psychological improvement

To account for potential baseline confounding, IPTW was applied using a logistic regression-based propensity score model. Baseline covariates included demographic characteristics, behavioral history, psychological symptom scores, and radiologic features. After weighting, the balance of covariates between the surgical and non-surgical groups improved substantially, as shown in the Love plot (Figure 6), with all absolute SMDs reduced to below 0.1.

Figure 6 Effect of surgery on psychological improvement after IPTW adjustment. (A) Covariate balance between surgical and non-surgical groups after IPTW, evaluated by absolute SMDs. All variables achieved post-weighting balance with SMDs <0.1. (B) Forest plot showing the IPTW-adjusted ORs and 95% CIs for surgery-associated improvement in anxiety, depression, and insomnia. CI, confidence interval; IPTW, inverse probability of treatment weighting; OR, odds ratio; PN, pulmonary nodule; SMD, standardized mean difference.

In the IPTW-adjusted pseudo-population, weighted logistic regression models demonstrated that surgery was significantly associated with psychological improvement across all three domains. Specifically, surgery was associated with a markedly higher likelihood of anxiety improvement (OR =15.80, 95% CI: 10.18–25.95), depression improvement (OR =7.38, 95% CI: 4.94–11.46), and insomnia improvement (OR =8.58, 95% CI: 5.60–13.77).

Surgical benefit among patients with small PNs (≤10 mm)

In patients with small PNs (≤10 mm), surgical intervention was consistently associated with markedly better psychological outcomes across all domains compared with surveillance (Figure 7).

Figure 7 Comparative symptom change distributions between surgical and surveillance groups. (A) Anxiety; (B) depression; (C) insomnia.

For anxiety, 41.6% of surgical patients improved vs. only 2.6% in the non-surgical group, while worsening occurred in 1.5% vs. 24.1%, respectively. Surgical patients accounted for 91.3% of all improvements and only 3.9% of worsening cases. For depression, improvement rates were 23.3% in the surgical group and 2.3% in the non-surgical group, with worsening substantially lower in surgical patients (2.5% vs. 18.2%). Surgical patients contributed 87.0% of all improvements and only 8.3% of worsening cases.

Similarly, insomnia improvement occurred in 21.3% of surgical patients compared with 1.7% in non-surgical patients, and worsening was less frequent in the surgical group (3.5% vs. 8.3%). The majority of improvements (89.6%) occurred among surgical patients, whereas most worsening cases (78.1%) were in the non-surgical group. These findings suggest that even among patients with small nodules often considered low-risk, surgical intervention is associated with significantly better psychological outcomes in anxiety, depression, and insomnia, compared to clinical observation alone.

Discussion

Key findings and explanations of findings

This study evaluated psychological distress among patients with newly detected PNs, specifically examining changes following different clinical management approaches. At baseline, we observed approximately a quarter to two-fifths of patients experiencing clinically significant anxiety (40.2%), depression (31.7%), and insomnia (24.6%), despite the absence of confirmed malignancy. These findings align with existing literature, suggesting that emotional distress among patients with PNs predominantly stems from diagnostic uncertainty rather than from disease severity itself (21-23).

Previous research has demonstrated that psychological distress can profoundly influence treatment decision-making in individuals with PNs (24-26), underscoring the importance of addressing anxiety during diagnostic evaluation. Further support comes from studies on patients with breast and thyroid nodules, where definitive pathological diagnosis has consistently shown superior efficacy in alleviating anxiety compared to observation or surveillance alone (27,28).

Our findings indicate that surgical resection significantly reduced anxiety symptoms 1 month after treatment, from 38.5% to 31.9% (P=0.046), whereas the surveillance group demonstrated no substantial improvement. This result provides strong evidence that unresolved diagnostic uncertainty itself may perpetuate anxiety. Indeed, anxiety persisted or worsened in approximately one-fourth (26.8%) of surveillance patients, despite their lesions being clinically classified as low-risk. This observation closely mirrors findings from major lung cancer screening trials, such as Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON) and National Lung Screening Trial (NLST), which noted persistent psychological distress even in cases with reassuring or benign imaging results (29,30).

Surgical resection may confer a psychological benefit by reducing perceived threat and resolving diagnostic ambiguity. Conversely, prolonged surveillance inherently extends the period of uncertainty, particularly among patients with indeterminate imaging findings, such as mixed GGO. Our data revealed that these patients were significantly more likely to continue experiencing anxiety, a finding that resonates with psychological theories emphasizing intolerance of uncertainty as a central contributor to cancer-related anxiety (31-34).

Our multivariate regression analysis identified female sex and younger age as robust, independent predictors of persistent anxiety, findings widely corroborated in both oncological and broader health psychology literature (35,36). Identifying these vulnerable subgroups early can guide targeted psychological interventions initiated at the point of nodule detection, regardless of subsequent clinical pathways.

Comparison with similar researches

Our findings differ from those of a recent prospective observational study by Wu et al., published in January 2025 (37), which reported no additional psychological benefit of surgery over follow-up among patients with indeterminate PNs. In that study, both surgical and follow-up groups demonstrated gradual improvement in anxiety and depression over a 1-year period, but surgery was not independently associated with greater symptom relief after multivariable adjustment.

Several factors may explain this discrepancy. First, the follow-up duration differed substantially; while Wu et al. focused on longer-term psychological adaptation over 1 year, our study captured early psychological trajectories within the first month after nodule detection and management. Second, differences in psychological assessment tools and analytic strategies [IPTW vs. propensity score matching (PSM)] may have influenced sensitivity to early symptom changes. Taken together, these findings suggest that the psychological impact of management strategies may be time-dependent and vary across different phases of the diagnostic and treatment pathway.

At the cohort level, both depression and insomnia grades significantly reduced 1 month after baseline in patients with LDCT-detected PNs (Wilcoxon, P<0.05). This finding contrasts sharply with previous studies, which have reported minimal or no improvement in mood and sleep disturbances among patients with PNs. For example, one study observed that depressive symptoms in early-stage lung cancer patients often remained stable or even worsened over time despite surgical treatment (11). Similarly, Tian et al. reported that sleep disturbances frequently persisted throughout the surveillance period and rarely resolved spontaneously (38).

Despite the significant overall improvement, the extent of change in depression and insomnia differed substantially between management strategies. Surgical resection was associated with greater psychological relief compared with radiological surveillance. In contrast, prolonged surveillance, by extending the period of uncertainty, was associated with a higher likelihood of persistent symptoms, particularly in patients with indeterminate imaging findings such as mixed GGO.

Beyond treatment strategy, patient demographic and clinical characteristics were also associated with differences in the trajectories of depression and insomnia. In our cohort, mixed GGO lesions were associated with a lower likelihood of depressive symptom remission, suggesting that radiologic ambiguity itself may contribute to sustained psychological burden. Several explanations may account for this persistence. Unlike anxiety, which is often triggered by immediate uncertainty (e.g., fear of malignancy), depression may reflect a more entrenched emotional state shaped by long-standing psychological vulnerabilities, poor coping mechanisms, and reduced resilience (39,40). Postoperative patients, although reassured about their diagnosis, may face new psychological stressors—including surgical recovery, functional limitations, and fear of recurrence—all of which can perpetuate depressive mood.

Furthermore, women and middle-aged adults (35–59 years) were more prone to persistent insomnia, potentially reflecting hormonal changes and heightened emotional reactivity during the peri-menopausal transition (41,42). Additionally, insomnia is frequently reported in patients with anxiety and depression, and neurobiologically, sleep disruption has been linked to dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity and altered cytokine profiles in cancer patients (43).

These findings underscore an important clinical implication: although depression and insomnia have traditionally been regarded as less responsive to short-term interventions, our results indicate that alleviation is more likely when diagnostic uncertainty is reduced and individual risk factors are addressed. Early identification and close follow-up of high-risk subgroups, such as women, middle-aged adults, and patients with ambiguous imaging features, are therefore essential for improving psychological outcomes and should be considered integral components of PN management.

Clinical implications and actions needed

Given the psychological outcomes, our study suggests several clinical implications for the management of patients with incidentally detected PNs.

First, the high prevalence of psychological symptoms even in the absence of confirmed malignancy supports the need for routine psychological screening at the time of nodule detection. The moderate prevalence of anxiety, depression, and insomnia underscores the emotional burden associated with ambiguous radiological findings and uncertain prognosis.

Second, although surgical intervention is primarily intended for diagnostic and therapeutic purposes, it may also offer psychological benefits, particularly alleviating anxiety. As our data demonstrate, anxiety significantly improved following surgery, likely due to resolution of diagnostic uncertainty and perceived action toward disease control. However, the trajectories of depression and insomnia appeared to be influenced by multiple factors beyond diagnostic resolution. Clinicians should consider routine screening for mood and sleep disturbances even after definitive surgical management, and provide appropriate referrals for further evaluation when indicated (44,45).

For patients under clinical surveillance, the psychological burden often persisted, despite a clinically low risk of malignancy. This highlights the importance of structured communication, clear explanation of imaging findings, and scheduled follow-up to reduce distress during the observation period. Additionally, surveillance strategies should integrate psychosocial support, particularly for high-risk subgroups such as women, younger patients, and individuals with mixed GGO, who consistently exhibited poor psychological trajectories in our cohort.

Third, from a health system perspective, incorporating mental health evaluation into PN clinics may reduce unnecessary surgery driven by anxiety and improve patient-centered decision-making. Providing psychoeducation, counseling, or referral to clinical psychology could help mitigate the emotional drivers of overtreatment, a known concern in nodule management.

Strengths and limitations

A key methodological strength of our study is the use of IPTW to control for baseline differences between the surgical and surveillance groups. IPTW produced balanced covariates (SMD <0.1) across both clinical (e.g., nodule size, radiologic features) and psychological (e.g., age, gender, baseline symptom scores) characteristics, consistent with recommended thresholds in the literature (46). Unlike PSM, IPTW preserved the full study cohort, enhancing statistical power and minimizing sample selection bias. The weighting process simulates a pseudo-randomized design by creating a pseudo-population where group assignment is independent of observed baseline covariates (47).

Compared with previous studies, our study offers two methodological advances: (I) a within-patient longitudinal design, capturing changes in the same individuals over time; and (II) a robust IPTW strategy, ensuring quasi-experimental balance without compromising cohort size. Previous studies used pre-post designs or unmatched comparisons, limiting their ability to attribute psychological outcomes to specific interventions (48). Our design integrates both within-participant longitudinal assessment and IPTW-based causal adjustment, enabling stronger inference about intervention effects while retaining full sample representativeness.

Despite its strengths, there are limitations in this study. First, the follow-up period was limited to 1 month, which may not fully capture long-term psychological changes or delayed responses to surgical or conservative treatment. Future studies with extended follow-up are needed to determine whether the observed improvements are durable. Second, the study was conducted at a single high-volume thoracic center, which may limit generalizability to other settings with different clinical protocols or patient populations. Future multicenter studies across diverse healthcare settings are needed to validate the reproducibility and external applicability of our findings. Third, although we adjusted for major confounders in multivariate analyses, residual psychological factors, such as resilience, uncertainty, and coping styles, were not assessed and may influence symptom trajectories. In addition, psychosocial factors, including marital status and socio-economic status, were not collected or adjusted for in the present study. These social determinants may influence patients’ psychological responses and questionnaire-based assessments, and their omission may have contributed to residual confounding. Future studies should incorporate psychological traits alongside socio-demographic factors such as marital status, socio-economic indicators, and social support measures to better characterize psychological vulnerability and enhance the interpretability and generalizability of findings in patients with PNs. Finally, although validated instruments were used to assess psychological status, formal psychiatric diagnoses were not made, and symptom changes were measured using self-report questionnaires. Future studies should include qualitative interviews or clinician-rated scales to triangulate patient-reported outcomes.

Conclusions

This study highlights distinct psychological trajectories in patients with PNs managed through surgery or surveillance. Notably, even in patients with small nodules typically considered low-risk, surgical resection was associated with markedly better psychological outcomes than clinical surveillance. Integrating psychological assessment and structured support early in clinical evaluation is crucial to address emotional distress, facilitate appropriate clinical decisions, and enhance patient care quality. Future longitudinal research is needed to refine targeted psychological interventions for this growing population.

Acknowledgments

The authors extend sincere gratitude to all the patients who participated in this study. We also acknowledge the staff of the Thoracic Surgery Department at The First Affiliated Hospital of Guangzhou Medical University for their assistance with patient recruitment and data collection.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1153/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1153/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1153/prf

Funding: This research was supported by the R&D Program of Guangzhou National Laboratory (No. SRPG22-017).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1153/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 protocol was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. 2021-190; date: 31 December 2021) and adhered to the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all participants prior to enrollment.

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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