Prognosis of segmentectomy and lobectomy for clinical T1c solid-dominant lung cancer

Introduction

The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) remains radical lobectomy, a procedure involving en bloc resection of the affected pulmonary lobe, ipsilateral hilar lymph nodes, and mediastinal lymph node dissection to ensure oncological radicality. In 1995, Ginsberg and Rubinstein conducted a randomized controlled clinical trial comparing lobectomy to local resection for early stage lung cancer with nodules ≤3 cm in diameter (1). Although the study established lobectomy as a superior radical treatment, it was unable to demonstrate the non-inferiority of sublobectomy due to limitations in case enrollment criteria and surgical instruments available at that time.

Since the beginning of the 21st century, the widespread use of low-dose spiral computed tomography (CT) has led to significant changes in the presentation of lung cancer, with an increasing number of cases being identified as early ground glass nodular lung cancer (2). The necessity of lobectomy for this type of tumor requires further investigation. Furthermore, advancements in surgical instruments and techniques have resulted in a growing preference among surgeons for local excision, as it allows for preservation of more healthy tissue. There has been increasing evidence on the feasibility of the use of anatomic segmentectomy in early-stage NSCLC (3-5).

In recent years, several clinical studies have provided precise measurements of the diameter and composition of pulmonary nodules included in the study. For instance, the enrolled lung nodule in JCOG0802 needed to be ≤2 cm, with a consolidation-to-tumor ratio (CTR) >0.5 (6). The results demonstrated a significantly superior overall survival (OS) rate for the segment resection group in comparison to the lobectomy group. JCOG1211 investigated the feasibility of segmentectomy in lung nodules with a long diameter ≤2 cm and CTR ≤0.5, as well as those with a long diameter >2 but ≤3 cm and CTR ≤0.5 (7). Based on the findings from these clinical trials, there has been a gradual expansion in the application of segmentectomy (8). While trials like JCOG0802 and JCOG1211 have defined the role of segmentectomy for smaller solid tumors and ground-glass opacity (GGO)-dominant lesions, respectively, robust prospective data are still lacking for the distinct subgroup of clinical T1c (2–3 cm) NSCLC that presents as solid-dominant (CTR >0.5). This specific radiological profile may indicate a more aggressive tumor biology compared to GGO-dominant nodules, raising questions about the suitability of sublobar resection. Therefore, this retrospective study was conducted to compare the oncological outcomes of segmentectomy versus lobectomy specifically in this under-investigated, solid-dominant cT1c patient population. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1068/rc).

Methods

Patients and data collection

Patients with NSCLC who underwent segmentectomy of the dominant pulmonary segment or lobectomy at Fudan University Shanghai Cancer Center between January 2008 and December 2021 were retrospectively enrolled. The eligibility criteria were as follows: (I) CTR >0.5; (II) tumor diameter >2 to ≤3 cm; (III) clinically confirmed N0 status (no regional lymph node metastasis); (IV) absence of prior or concurrent malignancies. Tumor staging was performed according to the American Joint Committee on Cancer (AJCC) 8th edition guidelines. Patients who have received neoadjuvant therapy or those with severe interstitial lung disease that impacts the surgical approach were excluded. Clinicopathological data, including gender, age, pathological tumor size, histological subtype, radiographic characteristics, surgical approach, tumor location, smoking history, and presence of visceral pleural invasion (VPI) or lymphovascular invasion (LVI), were extracted from electronic medical records and histopathology reports. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Ethics Committee and the Institutional Review Board of the Fudan University Shanghai Cancer Center (No. 2008223-9, 14 July 2020). Informed consent was waived due to the retrospective nature of the study and minimal risk to participants.

Definition of dominant pulmonary segments

The term “dominant pulmonary segments” designates anatomically stable segments frequently targeted for resection during segmentectomy. These include the dorsal segment (S6) of the lower lobes bilaterally, the lingular segment (S4+S5) of the left upper lobe, and other functionally demarcated segments (e.g., apical segments of the upper lobes). These segments are characterized by minimal anatomical variability and standardized vascular-bronchial patterns, rendering them technically favorable for surgical resection. Their anatomical consistency reduces intraoperative challenges such as aberrant vasculature identification or unexpected bronchial branching, thereby lowering surgical risks and procedural complexity. This predictability is particularly advantageous in preserving pulmonary function while ensuring oncological margins (9-11). At present, there is no accurate definition of the dominant pulmonary segment. Based on intraoperative anatomical assessments and consensus among our senior thoracic surgeons, the dominant pulmonary segments were defined as anatomically stable regions, classified into the following categories consistent with established anatomical criteria—right lung: individual segments (S1, S2, S3, S6, S8) and combined segments (S7+S8, S9+S10, S7+S8+S9+S10); left lung: individual segments (S1+S2, S3, S6, S8) and combined segments (S1+S2+S3, S4+S5, S7+S8+S9+S10) (S1, apical; S2, posterior; S3, anterior; S4, lateral; S5, medial; S6, superior; S7, medial basal; S8, anterior basal; S9, lateral basal; S10, posterior basal) The distribution of dominant lung segments in our cases is shown in Table 1.

Surgical procedure

In this study, segmentectomy was considered for clinically node-negative, peripheral tumors deemed technically suitable for complete resection with adequate margins based on preoperative imaging. Surgical margins were assessed in the resected specimens, and the procedure was switched to lobectomy if the margins were judged insufficient. All patients routinely underwent systematic hilar and mediastinal lymph node dissection; intraoperative lymph node examinations using frozen sections were mandatorily performed. If lymph node metastasis was detected intraoperatively, the procedure was switched to lobectomy.

Follow-up protocol

For all enrolled patients, the follow-up period commenced on the date of surgery. Postoperative surveillance included physical examinations, chest CT scans, abdominal/cervical/supraclavicular ultrasonography, and brain magnetic resonance imaging (MRI) or CT scans, performed at approximately 6-month intervals during the first 3 years, every 8 months between years 3 and 5, and annually thereafter. Additionally, whole-body bone scans were conducted at least once per year.

OS was measured from the surgical date until either death or the last follow-up visit. Recurrence-free survival (RFS) was defined as the duration from diagnosis to the first recurrence, death, or last follow-up. Patients who died from non-oncological causes were treated as censored observations in the RFS analysis.

Statistical analysis

Comparisons of baseline demographics and clinicopathological features were performed using Pearson’s χ² test or Fisher’s exact test for categorical parameters, and Student’s t-test or the Mann-Whitney U test for continuous variables, as appropriate. Survival curves for RFS and OS were generated using the Kaplan-Meier method, and differences were assessed with the log-rank test. A 1:1 nearest propensity score matching (PSM) were performed to ensure the robustness of the findings. Subgroup analyses were performed to identify potential risk factors for recurrence. All analyses were conducted using SPSS (version 25; IBM Corp., Armonk, NY, USA) and R (version 4.3.1; R Foundation for Statistical Computing, Vienna, Austria). A two-sided P value ≤0.05 was considered statistically significant.

Results

Patients’ characteristics

The inclusion criteria were met by 888 patients, among whom 833 patients received lobectomy and 55 patients received segmentectomy. Table 2 summarizes the characteristics of the 888 patients analysed.

Survival outcomes

The mean follow-up period for the entire cohort was 46.0±16.2 months (range, 0–165 months). Among 55 patients undergoing segmentectomy (SEG), 5 (9.1%) experienced recurrence, and 1 (1.8%) died from primary lung cancer, yielding a 5-year RFS rate of 89.0% (95% CI: 80.0–98.0%) and a 5-year OS rate of 91.7% (95% CI: 76.0–107.4%) (Figure 1). In contrast, among 833 patients treated with lobectomy (LOB), 215 (25.8%) developed recurrence, and 137 (16.4%) succumbed to lung cancer, corresponding to a 5-year RFS of 71.6% (95% CI: 67.9–75.0%) and a 5-year OS of 84.3% (95% CI: 81.1–87.4%). Unadjusted analyses demonstrated significantly better 5-year RFS rate [P=0.02; hazard ratio (HR): 0.726, 95% confidence interval (CI): 0.395–1.335] and OS rate (P=0.02; HR: 0.199, 95% CI: 0.081–0.489) in the SEG group (Figure 1).

Figure 1 Comparison of overall survival and recurrence-free survival between lobectomy and segmentectomy groups before propensity score matching. (A) Overall survival of LOB and SEG groups. (B) Recurrence-free survival of LOB and SEG group. LOB, lobectomy; SEG, segmentectomy.

Prognostic analysis for patients receiving lobectomy and segmentectomy following PSM

PSM (12) effectively balanced all baseline clinical variables between the LOB and SEG groups (Table 3). Post-PSM analyses revealed comparable 5-year RFS rates between LOB (81.4%; 95% CI: 70.2–92.6%) and SEG (89.0%; 95% CI: 78.5–99.5%), as well as similar 5-year OS rates (LOB: 88.1%; 95% CI: 75.4–100.8% vs. SEG: 91.7%; 95% CI: 82.3–101.1%) (Figure 2). Although a non-significant trend toward improved OS was observed in the SEG group (P=0.08), no statistically meaningful advantage was detected. Conversely, RFS outcomes demonstrated no significant intergroup difference (P=0.26) (Figure 2). Notably, numerical disparities in the number of at-risk patients at later follow-up intervals (e.g., 72 months) suggest potential variations in long-term survival dynamics or follow-up attrition, necessitating validation in larger cohorts to clarify clinical implications.

Figure 2 Comparison of overall survival and recurrence-free survival between lobectomy and segmentectomy groups after propensity score matching. (A) Overall survival of LOB and SEG groups after propensity score matching. (B) Recurrence-free survival of LOB and SEG group after propensity score matching. LOB, lobectomy; SEG, segmentectomy.

Subgroup analysis of RFS by surgical approach and pathological factors

This Cox proportional hazards analysis evaluated RFS outcomes in 888 patients with clinical T1c solid-dominant NSCLC (2–3 cm; CTR >0.5) undergoing SEG or LOB (Figure 3). Overall, no significant RFS difference was observed between SEG and LOB (HR: 0.47, 95% CI: 0.20–1.15; P=0.1). However, subgroup analyses demonstrated that SEG was associated with significantly improved RFS in patients without VPI (HR: 0.13, P=0.043) or LVI (HR: 0.12, P=0.03), suggesting its superiority in low-risk tumors (Figure 3). Conversely, LOB trended toward better outcomes in VPI-positive (HR: 1.36) or LVI-positive (HR: 2.67) subgroups, though statistical significance was not reached (Figure 3). Younger patients (≤65 years) also showed a tendency toward SEG benefit (HR: 0.15, P=0.06), while advanced disease stages (IB–IIIA) and nodal involvement (N1/N2) consistently favored LOB. Significant interaction effects were observed for VPI (P=0.04) and LVI (P=0.007), highlighting the critical role of pathologic risk stratification in surgical decision-making (Figure 3). These findings advocate for SEG in anatomically favorable, low-risk tumors (VPI/LVI-negative) and LOB in high-risk lesions, emphasizing the need for personalized treatment algorithms integrating preoperative imaging and intraoperative pathologic assessment.

Figure 3 Subgroup analysis of RFS by surgical approach and pathological factors. CI, confidence interval; CTR, consolidation-to-tumor ratio; HR, hazard ratio; LVI, lymphovascular invasion; mGGO, mixed ground-glass opacity; N, node; RFS, recurrence-free survival; sGGO, solid ground-glass opacity; T, tumor; VPI, visceral pleural invasion.

Discussion

Lobectomy is considered the standard procedure for the treatment of clinically operable stage IA NSCLC (1). This paradigm is now being refined by evidence from prospective trials supporting parenchymal-sparing resections. The JCOG0802/WJOG4607L trial in Japan established segmentectomy as a standard for small (≤2 cm), radiologically invasive (CTR >0.5) tumors (6), a finding complemented by the CALGB 140503 trial in the United States for peripheral T1a N0 NSCLC (13). Concurrently, for the less aggressive end of the spectrum, the JCOG1211 trial and our team’s subsequent publication in Translational Lung Cancer Research have demonstrated the efficacy of segmentectomy for GGO-dominant lesions (e.g., tumors ≤3 cm with CTR ≤0.5) (7). These findings underscore a paradigm shift toward parenchymal-sparing resections, driven by advancements in preoperative imaging (e.g., high-resolution CT) and minimally invasive techniques (e.g., robotic-assisted thoracoscopic surgery) (14,15).

Our present study specifically addresses the critical gap between these established indications by focusing on solid-dominant (CTR >0.5), clinically T1c (2–3 cm) invasive lung cancers. In this retrospective cohort, we compared segmentectomy and lobectomy for these intermediate-size, solid lesions and found segmentectomy to be non-inferior in terms of RFS after PSM, and even associated with a superior OS. Furthermore, while our study included cases of complex segmentectomy such as basilar segmentectomy (S7–10), which can be technically extensive, these procedures were rigorously performed as anatomical segmentectomies with the paramount goal of preserving functional lung parenchyma (e.g., the S6 segment) while achieving oncologic resection margins. This suggests that the oncologic efficacy of segmentectomy extends beyond smaller solid nodules (JCOG0802) and GGO-dominant nodules (16) to include selectively larger, solid-dominant tumors. However, the recurrence pattern analysis indicated that segmentectomy might be associated with a higher risk of recurrence in the presence of VPI or LVI, highlighting that meticulous patient selection remains paramount.

These results collectively align with the principle of precision oncology. Segmentectomy, when applied to anatomically favorable segments in appropriately selected patients (e.g., VPI/LVI-negative), preserves pulmonary function—sparing approximately 10–15% more lung parenchyma than lobectomy—without compromising oncologic outcomes. This approach may reduce postoperative morbidity and enhance quality of life, particularly in elderly or comorbid patients. The evolving evidence, from GGO-dominant to solid-dominant lesions, underscores a paradigm shift towards tailoring the surgical extent based on both tumor radiology and pathology.

There are several limitations that should be carefully considered when interpreting and generalizing the findings. First, its single-center retrospective design and the relatively small sample size in the segmentectomy group (n=55 even after matching) may limit the statistical power and generalizability of the findings. This limitation arises because lobectomy remained the standard approach for clinical stage I NSCLC during the study period, resulting in fewer segmentectomy cases. The limited sample size increases the risk of a type II error (i.e., failing to detect a modest true difference between procedures), and readers should be aware that the non-significant P values reported here do not necessarily demonstrate equivalence. Although PSM and statistical adjustments were applied, residual confounding cannot be entirely excluded. Second, treatment allocation was not randomized but determined based on individual clinical and anatomical considerations. For example, patients selected for segmentectomy more frequently had tumors located in anatomically favorable segments where sufficient resection margins could be achieved. This non-random selection introduced baseline imbalances between groups, which may affect outcome comparability. As such, caution is warranted when applying these findings to broader patient populations. Third, given the recent expansion of segmentectomy indications, the postoperative follow-up duration remains relatively short, especially for patients who underwent surgery in later years of the study. Consequently, long-term survival and recurrence data are still immature. Extended follow-up and accumulation of longitudinal evidence are essential to comprehensively assess the long-term outcomes of segmentectomy. Fourth, as with all retrospective observational studies, there is an inherent susceptibility to biases, particularly selection bias. While PSM was employed to minimize intergroup differences, the effectiveness of matching may have been constrained by the limited sample size, thereby affecting the robustness of the conclusions. Besides, information on the administration of adjuvant therapy was not comprehensively collected or analyzed in this retrospective study. This lack of data limits our ability to fully account for its potential impact on recurrence and survival, particularly in patients with adverse pathological features.

Conclusions

Despite these limitations, this study provides valuable real-world evidence supporting the role of segmentectomy in a well-defined subset of early-stage lung cancer patients. The results suggest that, in carefully selected individuals with T1c solid-predominant NSCLC, segmentectomy is non-inferior to lobectomy and may offer potential advantages in OS. By precisely excising the tumor-bearing segment while maximizing preservation of healthy lung parenchyma, segmentectomy maintains oncological safety and reflects the growing emphasis on precision and individualized thoracic surgical strategies. Although lobectomy remains the standard for cases involving multiple segments, central tumor locations, or high-risk features, this study supports the consideration of segmentectomy under specific conditions: when the tumor is situated in an anatomically accessible segment, preoperative staging confirms N0 disease, and a standardized segmentectomy with adequate margins can be performed. Future large-scale, multicenter, randomized controlled trials are necessary to further validate the long-term efficacy and safety of segmentectomy, particularly for larger tumors (>2 cm) containing GGO components.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1068/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1068/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1068/prf

Funding: The study was supported by the National Key R&D Program of China (No. 2022YFA1103900), National Natural Science Foundation of China (No. 82430099), the Clinical Research Special Project of Shanghai Municipal Health Commission (No. 202440070), and the Medical Research Special Project for Shanghai Science and Technology Innovation Action Plan (No. 24Y12800400).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1068/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, and was approved by the Institutional Review Board of the Fudan University Shanghai Cancer Center (No. 2008223-9). The requirement for informed consent was waived as it was a retrospective research.

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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