Comparison of patient-reported outcome measures (PROMs) after thoracoscopic lobar and sublobar resections for non-small cell lung cancer

Introduction

Current data show that patients with non-small cell lung cancer (NSCLC) stages I–IIA have a 5-year survival rate ranging from 90% in early stages to 65% in advanced stages (1). Lobar resection has been the standard treatment for early-stage lung cancer. However, recent studies revealed that sublobar resections are not associated with worse oncological outcomes in patients with stage IA NSCLC (2-4). With improved survival rates, the importance of postoperative health-related quality of life has been elevated as a crucial outcome, alongside oncological and perioperative results (5). Moreover, the potential decline in physical function is an important concern for patients undergoing lung surgery (5).

The reported difference in postoperative forced expiratory volume in the first second (FEV1) between sublobar and lobar resection in early-stage NSCLC patients ranged from 2% to 3.5%, a clinically insignificant difference favoring sublobar resections (3,4). However, the effect of preserving more lung parenchyma with sublobar resection cannot be fully evaluated through changes in FEV1 alone, and additional functional parameters should be investigated (6). Recently, patient-reported outcome measures (PROMs) for patients with NSCLC undergoing lung resection have been increasingly used to assess the long-term postoperative outcome (7-11). PROMs are a validated set of questions assessing the health-related quality of life, including patients’ functioning and symptoms (12). This study aimed to assess the effect of thoracoscopic sublobar vs. lobar lung resections on long-term changes in physical function, shortness of breath, and coughing in patients with NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-173/rc).

Methods

Study design

We analyzed prospectively collected data from October 2020 to June 2023 as part of the Value Based Health Care (VBHC) project at the Lung Tumor Center, University Hospital Basel. The VBHC project was developed in collaboration with Roche Pharma (Switzerland) Ltd. (Basel, Switzerland). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the local ethics committee (Ethikkommission Nordwest- und Zentralschweiz/Ethics Committee of Northwestern and Central Switzerland) under BASEC ID 2023-01582. Informed consent was obtained from all individual participants. The inclusion criteria for this subgroup analysis were: (I) age ≥18 years; (II) a signed University Hospital Basel general research consent form; (III) patients who underwent an anatomical lung resection via video-assisted thoracic surgery (VATS) for NSCLC with stage ≤ IIA, according to the 8^th tumor-node-metastasis (TNM) classification (13); and (IV) completing at least one quality of life questionnaire (at baseline, 3, 6, 12, or 24 months post-surgery). Patients were excluded if they had undergone surgical revision requiring thoracotomy, middle lobe resection, or previous ipsilateral anatomical lung resection. Some patients were included without an initial assessment of the quality of life and contributed only follow-up data.

Patient data were extracted from the project dataset. Perioperative data included age, sex, lung function test, history of comorbidities, NSCLC pathology, and the extent of lung resection. Lung function tests measured FEV1 and the diffusing capacity for carbon monoxide (DLCO). Comorbidities were recorded using standardized PROMs questionnaires [International Consortium for Health Outcomes Measurement (ICHOM) Standard Set Lung Cancer, version 4.0.0, revised: May 10^th, 2021], capturing histories of heart disease, high blood pressure, peripheral arterial disease, chronic lung disease, diabetes mellitus, kidney disease, liver disease, stroke, chronic neurological disease, depression, arthritis, and other cancers diagnosed within the previous 5 years. The indication for lung resection and its extension are made after discussion in the local interdisciplinary tumor board. PROMs were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 (version 3.0) and QLQ-LC29, both validated tools for assessing the quality of life in lung cancer patients (14-16). PROMs were evaluated at baseline and through follow-up questionnaires at 3, 6, 12, and 24 months post-surgery.

Patients were divided into two groups according to the extent of their lung resection: (I) lobar resection and (II) sublobar resection. Patients who underwent resection of the upper or lower lobe were classified as having undergone lobar resection. Sublobar resections included all other anatomical lung resections. Wedge resections were not included. Patients who underwent middle lobe resections were excluded, as the middle lobe consists of two segments, and sublobar resections of the middle lobe are uncommon.

The primary endpoint was the effect of the type of anatomical lung resection (lobar vs. sublobar) on postoperative changes in physical functioning, assessed by the physical functioning score of the QLQ-C30 at 3, 6, 12, and 24 months. Higher scores indicated better physical function (15). Secondary endpoints included the postoperative changes in symptom scores (e.g., shortness of breath and coughing) following lobar and sublobar lung resections, as measured by the QLQ-LC29 questionnaire at 3, 6, 12, and 24 months, where higher scores indicated more severe symptoms (16). We conducted a sub-analysis for patients with early-stage lung cancer with tumor diameter ≤2 cm (stage IA2).

Statistical analysis

Data were extracted from a database using Microsoft Excel (Microsoft^®, Redmond, WA, USA). Categorical variables are presented as numbers (n) and percentages (%), while continuous variables are reported as means ± standard deviations (SDs). Comparisons between the two groups were conducted using Fisher’s exact test for categorical variables and Student’s t-test for continuous variables.

We used linear mixed models to analyze all PROMs assessments for the entire study cohort to estimate treatment effects (lobar vs. sublobar resection) on both primary and key secondary outcomes (physical functioning score from the QLQ-C30, shortness of breath, and coughing from the QLQ-LC29). Treatment and time were included as categorical, along with an interaction term of treatment and time as fixed effects, while patient ID was included as a random effect into the model. Furthermore, we also included baseline scores as a fixed effect [analysis of covariance (ANCOVA)] to improve the precision of the estimates, given the subjectivity of the outcomes. We included additional variables (age >70 years, FEV1 <80%, and DLCO <80%) as covariates into the mixed models for the sub-analysis for patients with early-stage lung cancer (≤ stage IA2). A change of ≥10 points from baseline was considered clinically significant. For visualization, we plotted the treatment margins at each time point without adjusting for baseline assessments. All statistical analyses were performed using Stata [StataNow/SE 18.5 for Windows (StataCorp LLC, College Station, TX, USA)].

Results

Patient characteristics

A total of 57 patients were included in the study, 26 patients undergoing thoracoscopic lobar resection and 31 patients undergoing thoracoscopic sublobar resection. The mean age was 71.4±8.3 years in the lobar group and 70.7±10.5 years in the sublobar group (P=0.77). Thirteen patients (50%) in the lobar group and 18 patients (58%) in the sublobar group were male (P=0.60). No significant differences were observed in the preoperative lung function tests between the two groups. The mean FEV1 was 88%±17.1% in the lobar group and 83.4%±19.3% in the sublobar group (P=0.37), while the mean DLCO was 79%±18.2% in the lobar group and 78.5%±23% in the sublobar group (P=0.94). Adenocarcinoma was the most common pathology, found in 22 patients (85%) in the lobar group and 27 patients (87%) in the sublobar group (P>0.99). Patient characteristics are summarized in Table 1. Comorbidities were comparable between the two groups, with details provided in Table 2.

Changes in PROMs

The mean baseline physical functioning score was 78±23 in the lobar group and 73±30 in the sublobar group (P=0.44). No significant effect of sublobar resection compared to lobar resection was observed on changes in the physical functioning scores (P=0.76; Table 3). Furthermore, no decline in physical function was noted over time. There was no significant difference in physical function from baseline to 3 months postoperatively, nor during later follow-up assessments at 6, 12, and 24 months, with average changes ranging between −1.9 and 5.5 points and wide confidence intervals (CIs) (P=0.45, P=0.17, and P=0.15, respectively; Figure 1).

Figure 1 Postoperative changes in physical function scores (QLQ-C30) following thoracoscopic lobar and sublobar resections. No decline in the postoperative physical functioning up to 24 months compared to baseline following thoracoscopic lobar or sublobar resection. The average change ranged between −1.9 and 5.5 points, with wide CIs (P=0.45, P=0.17, and P=0.15, respectively). CI, confidence interval; QLQ, Quality of Life Questionnaires.

The mean baseline symptom scores for shortness of breath and coughing were 25±23 and 26±22 in the lobar group, and 24±21 and 25±25 in the sublobar group (P=0.90 and P=0.84, respectively). Analysis of the follow-up symptom scores for shortness of breath and coughing revealed no significant effect of the type of resection on changes in these scores (P=0.24 and P=0.73, respectively; Figures 2,3, Table 3). Additionally, there was no significant worsening of the symptoms up to 24 months postoperatively, with average changes ranging between −4 and 7.5 score points for shortness of breath and between −9.2 and 1.9 for coughing, with a wide CI that did not reach statistical significance (Figures 2,3, Table 3).

Figure 2 Postoperative changes in shortness of breath scores (QLQ-LC29) following thoracoscopic lobar and sublobar resections. No worsening of the postoperative shortness of breath up to 24 months after thoracoscopic lobar and sublobar resections. Time coefficients ranged from −4 to 7.5 score points, with wide CIs (P=0.48, P=0.27, and P=0.11, respectively). CI, confidence interval; QLQ, Quality of Life Questionnaires.

Figure 3 Postoperative changes in coughing score (QLQ-LC29) following thoracoscopic lobar and sublobar resections. No worsening of the postoperative coughing up to 24 months after thoracoscopic lobar and sublobar resections. Average changes ranged from −9.2 to 1.9 with large CIs (P=0.14, P=0.79, P=0.30, respectively). CI, confidence interval; QLQ, Quality of Life Questionnaires.

Sub-analysis for patients with early-stage lung cancer ≤ IA2

A total of 36 patients with NSCLC ≤ IA2 were included. There was no difference in the preoperative patients’ characteristics or history of comorbidities between the lobar and sublobar groups (Tables 4,5). The score analysis showed no significant difference in physical function during the follow-up assessments at 6, 12, and 24 months, with average changes ranging between −0.4 and −5.0 points (P=0.99, P=0.22, and P=0.94, respectively; Figure 4, Table 6). An improvement of physical function was detected after 6 months postoperatively in the sublobar group with average increase of 9.79 points (95% CI: 0.14 to 19.4, P=0.047), however this advantage could not be observed during the later follow-up assessments. Analysis of the follow-up symptom scores for shortness of breath and coughing revealed no significant effect of the type of resection (sublobar) on changes in these scores (P=0.14 and P=0.84, respectively; Figures 5,6, Table 6). A general worsening of shortness of breath scores of 16.4 points (95% CI: 0.78 to 32.10, P=0.040) in both groups could be observed in the follow-up assessment after 2 years postoperatively (Figure 5).

Figure 4 Postoperative changes in physical function scores (QLQ-C30) following thoracoscopic lobar and sublobar resections for patients with lung cancer stage ≤ IA2. No decline in the postoperative physical functioning at 6, 12, and 24 months in both groups, with average changes ranging between −0.4 and −5.0 points (P=0.99, P=0.22, and P=0.94, respectively. An isolated improvement of physical function after 6 months in the sublobar group with average increase of 9.79 points (95% CI: 0.14 to 19.4, P=0.047). CI, confidence interval; QLQ, Quality of Life Questionnaires.

Figure 5 Postoperative changes in shortness of breath scores (QLQ-LC29) following thoracoscopic lobar and Sublobar resections for patients with lung cancer stage ≤ IA2. Worsening of shortness of breath scores of average 16.4 points (95% CI: 0.78 to 32.10, P=0.040) in both groups, firstly after 2 years, without significant effect of the type of resection (P=0.09). CI, confidence interval; QLQ, Quality of Life Questionnaires.

Figure 6 Postoperative changes in coughing score (QLQ-LC29) following thoracoscopic lobar and sublobar resections for patients with lung cancer stage ≤ IA2. No worsening of the postoperative coughing up to 24 months after thoracoscopic lobar and sublobar resections. Average changes ranged from −3 to 12 with large CIs (P=0.77, P=0.27, P=0.67, respectively). CI, confidence interval; QLQ, Quality of Life Questionnaires.

The subgroups analysis showed that FEV1 <80% is associated with the worsening of postoperative coughing score with average 15.1 points (95% CI: 1.97 to 28.2, P=0.02; Table 6) and DLCO <80% is associated with average decrease in postoperative physical function of 14.2 points (95% CI: −26.5 to −1.84, P=0.02; Table 6). Age >70 years was not associated with significant changes in postoperative physical functioning, shortness of breath, or coughing (P=0.76, P=0.90, and P=0.71, respectively; Table 6).

Discussion

The main finding of this study indicates that there is no significant difference in patient-reported physical function between thoracoscopic sublobar and lobar resections for early-stage NSCLC, from 3 months to 2 years postoperatively. Shortness of breath and coughing were also not significantly affected by the type of resection during the follow-up period.

In a multicentric randomized trial, Lim et al. reported that thoracoscopic lobar resection for early-stage NSCLC was associated with improved postoperative recovery of physical function within 5 weeks compared to thoracotomy (10). Similarly, Heiden et al. demonstrated recovery of physical function 6 months postoperatively following both lobar and sublobar resections, including wedge resections for NSCLC, with no significant impact of the type of resection (9). Our findings are consistent with this pattern, as we observed no difference in physical function recovery between lobar and sublobar resections during the follow-up. In contrast, Stamatis et al. observed a permanent decline in physical function within 1 year after lobar resection for NSCLC, with superior recovery after sublobar resections. However, most of these procedures were performed via thoracotomy (8). In our study, where all operations were performed via thoracoscopy, physical function was recovered by 3 months and was maintained for up to 2 years, irrespective of the type of resection. However, we observed an improvement of physical function scores with average 9.79 points during the 6 months assessment for patients with early-stage NSCLC ≤ IA2 after sublobar resection. This advantage could not be further detected during the later follow-up assessments.

The analysis of the QLQ-LC29 symptom scores from 3 months to 2 years postoperatively showed no effect of resection type on patient-reported shortness of breath. Pompili et al. observed a mild deterioration in dyspnea following thoracoscopic anatomic lung resection, with approximately 30% of patients experiencing significant dyspnea during a follow-up period of 6 to 12 months, as assessed by the QLQ-LC13 (17). Similarly, Brunelli et al. showed that a substantial proportion of patients who underwent thoracoscopic anatomical lung resection for early-stage NSCLC experienced persistent dyspnea for up to 5 years postoperatively. Whereas, the incidence of dyspnea was reported to be lower after sublobar resections (7). In contrast, we did not observe a significant worsening of dyspnea in either group during the 2-year follow-up period. Jiang et al. reported worse dyspnea in patients after lobar compared to sublobar resection for NSCLC (18). Nonetheless, approximately 29% of their patients who underwent lobar resection had stages IIB to IVA cancer, which may have influenced their reported symptoms, whereas our cohort consisted of patients with earlier stages of NSCLC (18). In the sub-analysis for patients with NSCLC stage ≤ IA2 we observed a worsening of dyspnea of average 16.4 points during the assessment after 2 years after the operation.

Persistent coughing is a common issue among long-term survivors of NSCLC following anatomical lung resections (19). In our study, we found no significant difference in coughing scores between lobar and sublobar resections throughout the study period, starting at 3 months postoperatively. This aligns with findings from Lin et al., who reported no impact of resection type on coughing symptoms from 3 months postoperatively, though patients who underwent sublobar resection experienced faster recovery within the first month after surgery (20). In our cohort, which had a minimum follow-up of 3 months, no significant postoperative worsening of coughing could be observed during the 2-year study period.

We observed an association between decreased preoperative lung function tests and worse PROMs for patients with early-stage lung cancer ≤ IA2. This aligns with the finding from Khullar et al., who showed a significant deterioration of physical function for patients with low preoperative DLCO after minimally invasive lung cancer surgery (21). In our study, low preoperative DLCO was associated with decreased postoperative physical function. Furthermore, a low preoperative FEV1 was associated with an increased postoperative coughing.

Limitations

The primary limitation of this study is the relatively small sample size, which limits the ability to draw definitive conclusions and may overlook clinically significant differences. In addition, the small number of patients in certain subgroups prevented further analysis to compare both surgical techniques based on factors such as age, tumor size, preoperative lung functions, and the presence of comorbidities. Most patients included in the study exhibited good preoperative lung function, which prevented the analysis of outcomes in patients with more limited lung function. Beside that we observed an association between low lung function and decreased PROMs after the surgery for patients with early-stage lung function. However, a further analysis to investigate a possible benefit of sublobar resection for this group was not applicable due to the small number of patients. Another limitation is that while we included patients with NSCLC up to stage IIA, sublobar resection is not the standard treatment for NSCLC stage ≥ IA3, which may affect the generalizability of our findings. Furthermore, the criteria for performing sublobar resections were not documented, which may be affected by intraoperative findings, deep tumors, or the experience of surgeon. Another factor that may influence the PROMs is the occurrence of postoperative complication, which was not investigated in this study.

Conclusions

Thoracoscopic sublobar and lobar resections for patients with NSCLC were not associated with significant deterioration in physical function, increased shortness of breath, or coughing from 3 months to 2 years postoperatively. Additionally, no significant impact of the type of resection on postoperative changes in these outcomes was observed. This study highlights the value of standardized, disease-specific patient-reported outcome data collected throughout the course of treatment. Such data not only inform individual patient management but also enable aggregated analyses of various subgroups that support the implementation of value-based, patient-centered care (22).

Acknowledgments

The study data were collected as part of the internal Value Based Health Care (VBHC) program for lung cancer at University Hospital Basel.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-173/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-173/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-173/prf

Funding: The PROMs project was developed with financial support from Roche Pharma (Switzerland) Ltd.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-173/coif). M.H. reports that the study data were collected as part of the internal Value Based Health Care (VBHC) program for lung cancer at University Hospital Basel. The project was developed in collaboration with Roche Pharma (Switzerland) Ltd. The other 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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the local ethics committee (Ethikkommission Nordwest- und Zentralschweiz/Ethics Committee of Northwestern and Central Switzerland) under BASEC ID 2023-01582. The Ethics Committee of Northwestern and Central Switzerland serves as the ethics review board for University Hospital Basel, which does not have an internal ethics committee. 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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