Is segmentectomy a viable option for small-sized peripheral non-small-cell lung cancer?

We commend Drs. Hattori et al., for their meticulous randomized, controlled trial comparing segmentectomy and lobectomy in patients with small-sized peripheral non-small-cell lung cancer (NSCLC) with a radiologically pure-solid appearance, a post-hoc supplemental analysis. This study aimed to evaluate overall survival, relapse-free survival, causes of death, and recurrence patterns in patients with radiologically pure-solid NSCLC undergoing segmentectomy or lobectomy. The objective was to explore why segmentectomy demonstrated superior overall survival to lobectomy, even in oncologically invasive lung cancer (1). It is important to note that in this post-hoc analysis, ground-glass opacity (GGO) and tumors with semi-solid appearances commonly considered less aggressive were excluded. By focusing on radiologically pure-solid tumors, the study provides a more stringent comparison of segmentectomy and lobectomy for more invasive forms of NSCLC.

A total of 553 patients were included in this post-hoc analysis. Among them, 274 (50%) underwent lobectomy and 279 (50%) underwent segmentectomy between August 2009 and October 2014. With a median follow-up of 7.3 years, the 5-year overall survival rate was significantly higher in the segmentectomy group compared to the lobectomy group [92.4% vs. 86.1%; hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.41–0.97; P=0.033]. However, the 5-year relapse-free survival was similar between the two groups (82.0% vs. 81.7%; HR 1.01; 95% CI: 0.72–1.42; P=0.94). The number of lung cancer-related deaths was comparable between both groups. However, non-cancer-related deaths were reported in 35 patients (13%) following lobectomy, compared to 19 patients (7%) after segmentectomy. Segmentectomy was associated with a higher rate of locoregional recurrence (45 patients, 16%) compared to lobectomy (21 patients, 8%) (P=0.0021). Subgroup analyses revealed that segmentectomy provided superior 5-year overall survival compared to lobectomy in patients aged 70 years or older 85.6% vs. 77.1% (P=0.013) and in male patients 92.1% vs. 80.5% (P=0.0085). In contrast, better 5-year relapse-free survival after lobectomy than after segmentectomy was observed in younger than 70 years (87.4% vs. 84.4%; P=0.049) and in female patients (94.2% vs. 82.2%; P=0.047). These findings are consistent with the results of their previous study (2).

Lobectomy has been the standard surgical procedure for lung cancer treatment for decades. However, the advent of computed tomography screening programs (3,4) and enhanced follow-up strategies have facilitated the earlier detection of very small NSCLC, leading to the proposal of parenchyma-sparing treatments, such as sublobar resections, not only for high-risk surgical patients but also as a means of preserving lung function. Sublobar resections include wedge resection and segmentectomy. Segmentectomy involves the dissection of the artery, vein, and bronchus supplying the segment, with the peripheral ends of these structures included in the resected specimen. In some cases, however, the vein may be preserved depending on the anatomical considerations. Compared to wedge resection, segmentectomy offers hilar and intersegmental lymph node dissection, ensuring a more complete oncological assessment (5). In recent years, this surgical technique has become increasingly popular and a viable surgical option for tumors with pure GGO <2 cm, adenocarcinoma in situ <2 cm, or minimally invasive or invasive adenocarcinoma <2 cm (6). Two recent randomized controlled trials with a 7-year follow-up (2,7) demonstrated the non-inferiority of sublobar resections compared to lobectomy for small peripheral stage IA NSCLC. However, the superiority of segmentectomy has not been established for centrally located small tumors, where lobectomy remains the standard treatment.

One of the key strengths of this study is its large sample size and the rigorous methodological approach, including randomization and central monitoring. The long follow-up period of 7.3 years adds robustness to the survival data. However, the main limitation of this study lies in its post-hoc nature. As this type of analysis is carried out after primary data collection and is not predefined in the study design.

Hattori et al. showed that the number of deaths unrelated to the primary cancer was higher after lobectomy than after segmentectomy (1). A larger parenchymal resection is likely to have a greater impact on postoperative recovery. Wang et al. demonstrated in their meta-analysis that segmentectomy provides comparable survival outcomes with less post-operative complications when compared to lobectomy in elderly patients (8). According to Hattori et al., segmentectomy was associated with a significantly higher 5-year overall survival rate in male patients and those over 70 years old. This is particularly relevant, as these patients often have comorbidities, especially cardiovascular conditions, which make them more vulnerable and frailer. In the landmark study by Saji et al., a marginal disparity in forced expiratory volume in one second (FEV1) reduction between the two groups was observed, but this difference was minimal (2 vs. 3.5%) (2). As highlighted by Boujibar et al., these markers are nowadays outdated for the proper assessment of patients’ respiratory function (9). It is likely that other more clinically relevant markers could be used to highlight a decline in postoperative recovery (10).

Although overall survival is better in the segmentectomy group, authors demonstrated that the locoregional recurrence rate is higher after segmentectomy compared to lobectomy [45 (16%) vs. 21 (8%); P=0.0021] (1). In their first study, the locoregional recurrence rate after segmentectomy was only 10.5% (2). Another study focusing on GGO or predominantly ground-glass lesions found a 5-year relapse-free survival rate of 98% (95% CI: 95.9–99.1%) after segmentectomy (11). To minimize the risk of locoregional recurrence and ensure adequate resection margins, the use of three-dimensional (3D) reconstructions has proven invaluable in the preoperative planning of segmentectomies. These reconstructions allow precise localization of the target nodule and help define safe resection margin, reducing the risk of residual disease (12). In preoperative planning, 3D reconstructions support surgeons in deciding between segmentectomy and lobectomy for a personalized surgical strategy (13).

In conclusion, segmentectomy should be considered the standard surgical procedure for managing early-stage, peripheral NSCLC in specific subgroups, particularly in elderly and male patients, unless contraindicated. The findings from Hattori et al. demonstrate superior overall survival for these populations following segmentectomy, although the increased risk of locoregional recurrence remains a concern. Preoperative planning with advanced techniques, such as 3D reconstructions, is crucial for ensuring safe resection margins and minimizing recurrence risk. In contrast, lobectomy may still be preferred for younger patients and females due to better relapse-free survival outcomes. This highlights the need for personalized surgical strategies based on individual patient profiles, ensuring both oncological safety and optimal functional outcomes.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.

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Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2151/coif). The authors have no conflicts of interest to declare.

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