Right upper lobectomy versus left upper trisegmentectomy and middle lobectomy versus lingulectomy: real-world post-operative and oncological outcomes

Introduction

Lung cancer is the leading cause of cancer death worldwide (1). For early-stage non-small cell lung cancer (NSCLC), surgical resection is considered the gold standard treatment; however, the optimal extent of the surgical resection for these tumours is still matters of debate among the thoracic surgeons. In fact, the recent JCOG0802/WJOG4607L trial illustrated how for peripheral tumours less or equal to 2 cm anatomical segmentectomy is non-inferior to lobectomy with respect to overall survival (OS), while having similar 5-year relapse-free survival (2). Similarly, the CALBG 140503 trial showed that sublobar resection in patients with pN0 tumours ≤2 cm was not inferior to lobectomy in terms of disease-free survival (DFS), and had similar results in terms of OS (3).

The left upper lobe might be divided in two major anatomical units: the left upper division, or culmen, made by segments I to III, and the lingula, which is made by segments IV and V, thus being one of the largest lobe. These anatomical components might be compared to right upper lobe, also made by three segments (I–III), and the middle lobe (segments IV–V), respectively (4).

Although early-stage NSCLC in the right upper lobe or in the middle lobe are rarely resected through a bilobectomy, early-stage tumours in the left upper lobe are more often resected by a left upper lobectomy, even when they only involve the culmen or the lingula.

The resection of the left upper division alone or the lingula might provide a lung-sparing alternative to left upper lobectomy, without impairing long-term survival outcomes.

Therefore, to determine whether a lingulectomy (LL) or a left upper trisegmentectomy (LU3S) alone are as safe and oncologically-effective as a middle lobectomy and a right upper lobectomy (RUL), respectively, for NSCLC, we performed a retrospective study comparing short and long-term outcomes among these procedures. We present this article in accordance with the STROBE reporting checklist (available at https://asj.amegroups.com/article/view/10.21037/asj-25-51/rc).

Methods

Patients selection

Our study is a retrospective cohort study; we collected all consecutive patients from our retrospective databases who underwent an LL, LU3S, middle lobectomy or RUL for NSCLC at an Italian high-volume centre (Azienda Ospedale Università di Padova, Padova, Italy) between February 2016 and December 2023. All procedures were performed through video-assisted thoracoscopic surgery (VATS) approach. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Board of University Hospital of Padova (3812/AO/16) and individual consent for this retrospective analysis was waived.

Patients with other previous or concurrent primary cancers, patients with small cell lung cancer (SCLC) or clinical evidence of nodal disease, clinical and pathological T3–T4, or stage IV metastatic disease, according to the 8^th edition of the tumor-node-metastasis (TNM) classification of malign tumours (5), and patients without complete pathological resection were excluded from the study.

Patients were divided in four groups according to surgical procedure: LU3S, left LL, right middle lobectomy (RML), and RUL. We compared the LU3S to the RUL groups, and the LL to the RML groups.

Patients operated on before the adoption of the 8th edition of the TNM classification of malignant tumours were restaged according to the 8th edition. Patients were characterized according to demographic variables, including age, sex, smoking history (never, former, current); clinical variables, such as comorbidities, assessed through the Charlson Comorbidity Index (6), body mass index (BMI), forced expiratory volume in 1 s (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), tumour histology and diameter, and clinical and pathological stage.

Outcomes

Primary outcomes of this study were OS, recurrence rate, and DFS at 3 and 5 years after surgery. Secondary outcomes were length of hospital stay (LOS), length of drainage (LOD), postoperative complication rate, post-operative mortality at 90 days, lymph node yield, surgical time, conversion rate, and resection margins.

Follow-up

Patients were followed up after surgery according to institutional guidelines. The first follow-up visit was scheduled 3 months after surgery, then every 6 months for the first 2 years after surgery, then annually thereafter. At each follow-up visit, patients underwent a physical examination and a total body computed tomography. Positron emission tomography integrated with computed tomography was performed if recurrence was suspected based on imaging findings. Patients were defined as lost to follow-up when they did not return for at least two consecutive follow-ups and the study team was unable to reach them. A total of 8 patients were lost at follow-up, 6 in the RUL cohort, 1 in the RML cohort, and 1 in the LL cohort, which were included in the analysis and censored at the date of their last known contact.

Recurrence was defined as the presence of new lesions on imaging consistent with metastatic disease along with a biopsy confirmation if possible. Sites and dates of the first recurrence were recorded. OS was determined as the time from surgery until death from any cause or loss to follow-up. Patients who did not die during the observation period were censored at the date of the last available follow-up. DFS was defined as the time from surgery until recurrence or death from any cause.

Surgical technique

All surgical procedures were performed by the board-certified surgeons in our centre. All surgeries were performed through VATS approach; in 90% of patients, we used a 3-port anterior approach, and only in 10% of VATS surgery we used a 2-port approach. Regarding the 3-port anterior approach, it was performed according to the Copenhagen technique, as reported by Henrik J. Hansen and René H. Petersen (7).

As suggested by the European Society of Thoracic Surgeons (ESTS) guidelines for intraoperative lymph node staging in NSCLC and the International Association for the Study of Lung Cancer Staging Project (IASLC) (8,9), systematic lymphadenectomy was performed in every surgery, with the resection of at least three N2 stations, one of them always represented by station 7, and at least three N1 stations, including the hilar and intersegmental stations.

Statistical analysis

The characteristics of this study’s population are reported using numbers and percentages or median and interquartile range (IQR). Between-group differences were evaluated using the Fisher’s exact test for categorical variables and the Wilcoxon-Mann-Whitney test for continuous variables. OS and DFS were estimated using the Kaplan-Meier curves.

All statistical tests were two-tailed, and P values <0.05 were considered statistically significant. All analyses were carried out using GraphPad Prism version 9.5.1 (528).

Results

Patients’ characteristics

A total of 263 patients were included in the study, 162 of them underwent an RUL, 39 an LU3S, 44 an RML, and 18 an LL. The mean age of the entire population was 68 years (SD: ±10 years), and 50.6% (n=133) were women.

Patient demographics, comorbidities, and surgical variables are listed in Tables 1,2.

Between the LU3S and RUL groups, and the RML and LL groups, there were no statistically significant differences in terms of demographic characteristics, comorbidities, pre-operative respiratory function, BMI, and tumour histology. The predominant histologic type was adenocarcinoma in all groups.

The majority of patients in the RUL cohort were clinical IA3, at 35.8% (n=58), while in the LU3S cohort they were clinical IA2, at 43.6% (n=17). There were no significant differences in the clinical staging among the LL and the RML groups. Within the LL group, 22.2% (n=4) of patients had a pathological N2 disease (stage IIIA), while only 2.3% (n=1) had a mediastinal nodal metastasis in the RML group (P=0.008).

Primary outcomes

The mean follow-up period was 45 months in the whole series, 49 months for the RUL patients, 44 for LU3S, 38 for LL, and 35 for the RML patients. A total of 8 patients were lost at follow-up, 6 in the RUL cohort, 1 in the RML cohort, and 1 in the LL cohort. At the end of the follow-up, 239 (90.9%) patients were still alive. Out of the 24 deaths, 13 in the RUL group, 6 in the LU3S group, 2 in the RML group, and 3 in the LL group, 9 deaths were lung cancer related (7, 1, and 1 death in the RUL group, RML group, and LL group, respectively), the rest were non-cancer related.

There was no statistically significant difference in OS either between the RUL and LU3S groups (3-year OS: 91.6% vs. 79.5%; 5-year OS: 90.3% vs. 79.5%, respectively; P=0.07), and between the RML and the LL groups (3-year OS: 94.3% vs. 83.3%; 5-year OS: 94.3% vs. 83.3%, respectively; P=0.10), as illustrated in Table 3 and Figure 1. Subgroup analysis according to pathological stage > IA2 also did not show significant differences in OS between the RUL and LU3S and between the RML and LL groups (Table 3; Figure 2).

Figure 1 Overall survival (A) and disease-free survival (B) in the RUL and LU3S cohort, and in the RML and LL cohort. LL, lingulectomy; LU3S, left upper trisegmentectomy; RML, right middle lobectomy; RUL, right upper lobectomy.

Figure 2 Overall survival (A) and disease-free survival (B) for pathological stages > IA2 in the RUL and LU3S cohort, and in the RML and LL cohort. LL, lingulectomy; LU3S, left upper trisegmentectomy; RML, right middle lobectomy; RUL, right upper lobectomy.

Similarly to OS, there were no statistically significant difference in DFS among the RUL and LU3S groups (3-year DFS: 83.4% vs. 76.4%; 5-year DFS: 79.2% vs. 76.4%, respectively; P=0.58), and between the RML and the LL groups (3-year DFS: 95.2% vs. 82.4%; 5-year DFS: 95.2% vs. 82.4%, respectively; P=0.09) (Table 4; Figure 2). Subgroup analysis according to pathological stage > IA2 also did not show significant differences in DFS between the RUL and LU3S and between the RML and LL groups (Table 4; Figure 2).

Regarding the recurrence rate, a total of 34 patients (12.9%) had a recurrence, most of them were distant recurrences. The distant recurrences in the whole cohort occurred mainly in the contralateral lung, contralateral lymph-nodes, bone, and brain.

There were no significant differences in recurrence rate between RUL patients, at 15.4% (n=25), and the LU3S patients, at 17.9% (n=7) (P=0.81) (Table 3), or between the RML and the LL patients (2.3% vs. 5.9%, respectively; P=0.49) (Table 4).

Secondary outcomes

There was no statistically significant difference between the RUL and LU3S group in terms of LOS, LOD, postoperative complications, and post-operative mortality at 90-days, as illustrated in Table 5.

Five cases (3.1%) were converted to open surgery in the RUL cohort, and 2 cases (5.1%) in LU3S cohort (P=0.06).

Surgical time was similar among the two groups, at a median of 125 minutes (IQR, 52.5 minutes) for the RUL compared to 115 minutes (IQR, 52.5 minutes) for the LU3S (P=0.37).

There were no significant differences in the resection margin free of disease among the RUL and LU3S groups [25 (IQR, 25) vs. 20 (IQR, 18.5) mm, respectively; P=0.17].

Compared to the RUL, LU3S was associated with a higher median of lymph nodes harvested overall [8 (IQR, 5.5) vs. 12 (IQR, 8.5), respectively; P<0.001], mediastinal [4 (IQR, 2) vs. 5 (IQR, 4), respectively; P=0.005], and hilar [3 (IQR, 3) vs. 6 (IQR, 6), respectively; P<0.001].

The median LOS in the LL group was double the days than in the RML group [6 days (IQR, 1 days) vs. 3 days (IQR, 2.25 days), respectively; P<0.001]. Aside from the LOS, there were no significant differences among the LL and RML groups in LOD, postoperative complications, and post-operative mortality at 90 days, as illustrated in Table 6.

Only one case (2.3%) was converted to open surgery in the RML cohort, while the conversion rate in the LL cohort was 0% (P=0.51).

There was no statistically significant difference between RML and LL in surgical time [105 (IQR, 40) vs. 120 (IQR, 46.25) minutes, respectively; P=0.24].

The median resection margin free of tumour was similar among the groups, at 15 mm (IQR, 10 mm) in the RML cohort compared to 11 mm (IQR, 27.5 mm) in the LL cohort (P=0.96).

Lymph node yield was better in the LL group compared to the RML group, with a median of lymph nodes harvested overall of 14 (IQR, 5.75) vs. 7 (IQR, 3), respectively (P<0.001); hilar lymph nodes of 6.5 (IQR, 4.75) vs. 3 (IQR, 2), respectively (P<0.001); and mediastinal lymph nodes of 6 (IQR, 4.5) vs. 3.5 (IQR, 2), respectively (P<0.001).

Discussion

The role of segmentectomy for the treatment of early stage <2 cm NSCLC has been well established in the Japanese and American multicenter randomized trials (2,3). However, not all the segments are equal; in fact, we can distinguish different types of segmentectomy based on the number of segmental plans and on the number of segments to resect: simple segmentectomy, which requires the dissection of only one intersegmental plan, or complex segmentectomy (two or more intersegmental plans), and single or multi- (more than one segment) segmentectomy. According to JCOG0802 trial results (2), simple segmentectomies are easier procedures compared to complex segmentectomies, and they are associated with lower surgical times and complications rate. LU3S and LL are considered as simple segmentectomies and they are well established standard procedures in general thoracic surgery often performed by thoracic surgeons worldwide. The left upper three-segments and lingula actually represent two autonomous and well distinguished anatomical structures, owning independent arterial and venous vascularization and a separate bronchial branch each (4). From an anatomical point of view, the left upper division might represent the equivalent of the right upper lobe, while the lingula can be compared to the middle lobe; in fact, they have the same number of segments and similar anatomical patterns, not to mention that in many patients the minor fissure of the right lung is not well developed or completely absent. For this reason, the resection of the left upper division with preservation of the lingula is the anatomical counterpart of an right upper lobe sparing the right middle lobe. This theory is supported by many authors, such as Huock et al. (10) in their surgical series, where they suggested that LU3S with sparing of the lingula is a safe and reasonable operation for early-stage left apical NSCLC. However, in a tumor larger than 2 cm located in the right upper lobe, the gold standard treatment would be an RUL rather than a bilobectomy. Conversely, in the same conditions on the left side, a left upper lobectomy would be proposed, despite a culmenectomy or LL with satisfying free surgical margins would be feasible. The intention of our study is to understand the feasibility from a surgical and oncological point of view of performing a culmenectomy or LL, also for tumors with clinical stage > IA2. For this reason, we divided our study population in four groups, RUL, LU3S, RML, and LL, comparing the RUL to the LU3S cohort, and the RML to the LL cohort, respectively.

No differences were observed in mean tumor diameter between the lobectomy and segmentectomy groups; culmenectomy was more often performed for clinically IA1, IA2 stages (n=22: 56.4%), while the majority of patients undergone a RUL were clinical-stage T1cN0 (IA3), at 35.8% (n=58); both LL and RML were mostly performed for cT1bN0 (IA2) stage (50% vs. 45.5%, respectively; P=0.74).

Dealing with ‘early’ NSCLC stages (I–IIA), all the procedures were approached minimally invasively. We report a low global conversion rate (8 over 263 patients; 3%), with no significant differences between segmentectomies (n=2, 5.1%) and lobectomies (n=6, 5.4%).

Some authors described similar surgical times after segmentectomy and lobectomy (11); conversely, we report a trend towards longer surgical times in the RUL group [125 minutes (IQR, 52.5 minutes)] compared to the LU3S group [115 minutes (IQR, 52.5 minutes)], although this difference did not result statistically significant (P=0.37).

One of the main segmentectomy-related issue reported by many authors is the extent of the lymphadenectomy, especially of N1 intrafissural lymph nodes which may not be removed during segmentectomy; as a consequence, the disease might be under-staged, not allowing patients who would benefit from adjuvant therapy to receive it. In their study, Aprile and colleagues (12) reported different cases of LU3S, with inadequate lymph node dissection. In our population, we noted that the quality of hilar and mediastinal lymph-node dissection was still high in the segmentectomy groups. In fact, we reported an higher median number of total lymph nodes removed in the segmentectomy groups, at 12 (IQR, 5) in LU3S and 14 (IQR, 5.75) in the LL group, compared to 8 (IQR, 5.5) in the RUL and 7 (IQR, 3) in the RML group, respectively, with a statistically significant difference between the groups (P<0.001). Moreover, LU3S and LL were associated to higher number of both N1 and N2 lymph nodes removed compared to the respective lobectomy (RUL and RML), again with a statistically significant difference among the groups (P<0.001). In our opinion, this result is relevant because it suggests that lymphadenectomy can be done adequately also during a segmentectomy. The increased sampling of hilar and mediastinal lymph nodes in our population may be the result of our great experience in minimally invasive surgery. In fact, since we performed our first VATS lobectomy and segmentectomy in 2013 and 2015, respectively, in the last 10 years, the majority of our major surgical procedures for lung cancer have been performed through VATS approach, while conversion to open surgery has gradually become a very rare event.

Interestingly, also post-operative results in our population are encouraging. In fact, no differences were observed in terms of LOS (P=0.29) and LOD (P=0.34) among the RUL and LU3S groups.

Similarly to other authors (11-16), we didn’t find any statistically significant difference in surgery-related post-operative complications between the groups: prolonged air leaks (PAL) occurred in 5 (12.8%) and 17 (10.5%) patients in LU3S and RUL group, respectively (P=0.63), with the development of subcutaneous emphysema in 21 patients (13%) in the RUL cohort and 1 patient (2.6%) in the LU3S cohort (P=0.06). Only for this one patient in the LU3S group, a reoperation was necessary to perform aerostasis, while no patient needed a reoperation in the RUL group.

Regarding RML and LL groups, there were no significant differences in post-operative complications among the groups, and LOD was about 2 days in both procedures, with no significant differences reported (P=0.09); conversely, we observed an higher LOS in the LL group compared to RML [6 (IQR, 1) vs. 3 (IQR, 2.25) days], with a statistically significant difference between the two (P<0.001). The longer LOS in the LL group was not consequential to surgically-related complications, as demonstrated by the shorter LOD duration in the same group, but it could be the result of a more frail population, as confirmed by the higher mean Charlson Comorbidity Index in this group [5 (IQR, 2)].

Finally, in our cohort, there were no significant differences in 3- and 5-year OS either between the RUL and LU3S groups (P=0.07), and between the RML and the LL groups (P=0.09). Similarly, no differences were reported in DFS among the groups, nor in recurrence rate. Our findings are in line with what other authors reported in their research (12-15); Aprile and colleagues (12) performed a retrospective study comparing LU3S, LL and left upper lobectomy for NSCLC, and they found comparable oncologic outcomes, with no difference in OS (P=0.82) and DFS (P=0.56); Witte et al. (13), in their pair matched control study comparing left upper lobectomy with both LL and culmenectomy, did not find differences between the procedures in OS (P=0.9) and DFS (P=0.3). Furthermore, similarly to our study, their research includes patients with a tumour diameter wider than 2 cm and with pathological nodal involvement, suggesting that culmenectomy and LL, when feasible with good margins free of tumour, might be considered as an oncologically-safe alternative to left upper lobectomy also in patients with tumours larger than 2 cm or with potential nodal involvement.

Limitations of the study

The present study has several limitations. Firstly, there might be a selection bias among the groups due to the retrospective assignment of the patients to surgical arms, and due to its single-centre nature. Secondly, the lack of randomization in this study means that the two groups could differ both on measured and unmeasured factors. Most importantly, the numerosity of our population is not consistent among the groups; in fact, over 263 patients in total, more than half undergone an RUL, and only 18 patients underwent an LL. Lastly, no standardized criteria were used in choosing the surgical procedure, this decision was ultimately left to the surgeon’s personal judgment and expertise.

Conclusions

In our study, multi-segmentectomies, such as LL and LU3S, were associated with comparable long-term oncological outcomes and similar short-term outcomes compared to their anatomical counterparts, RML and RUL, respectively. Our results suggest that multi-segmentectomies are as oncologically and surgically feasible as RML or RUL, even for tumours staged > IA2.

Further and larger prospective studies are warranted to confirm our findings.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://asj.amegroups.com/article/view/10.21037/asj-25-51/rc

Data Sharing Statement: Available at https://asj.amegroups.com/article/view/10.21037/asj-25-51/dss

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-25-51/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-25-51/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Ethics Board of University Hospital of Padova (3812/AO/16) and individual consent for this retrospective analysis was waived.

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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