Current state of anatomic lung resection in the management of early-stage non-small cell lung cancer. a narrative review

Introduction

Background

Lung cancer is the second most common malignancy in both males and females with an estimate of 226,650 new cases in the United States in 2025 alone (1). The World Health Organization estimated 2.5 million new cases yearly of lung cancer worldwide (2). However, lung cancer is the leading cause of cancer related mortality, with an estimated 124,730 death in the US this year, exceeding that of breast, prostate, colon and rectal cancers combined (1). According to the American Cancer Society, mortality has slowly decreased since the 1990s in men and 2000s in women, largely attributed to declining prevalence of smoking (1).

In the management of lung cancer, staging is paramount for selection of the appropriate treatment. The new 9^th edition of the American Joint Committee on Cancer staging system was released in 2025 (3). Although the latest edition redefined lung cancer staging in the N and M parameters, only minor changes have been made to the T component and thus it does not significantly impact interpretation of previous data regarding stage IA non-small cell lung cancer (NSCLC).

Rationale and knowledge gap

Although surgery has been universally accepted as a standard of care for stage IA NSCLC, there is no consensus on the appropriate extent of surgical resection. Early landmark studies suggested that lobectomy, as opposed to sublobar resections, results in a lower rate of recurrence (4). However, recent trials have demonstrated noninferior outcomes with sublobar resections in small, less than 2 cm peripheral cancers (4-8). Notably, despite noninferiority design, JCOG0802 trial demonstrated even superior 5-year overall survival (OS) in segmentectomy group (95% vs. 91%). An important contextual factor to consider is the release of the National Lung Screening trial in 2010, which lead to wide adoption of screening practices and lung cancer detection at earlier stages. According to the United States Preventative Service Task Force, the current recommendation for annual screening with a low-dose spiral computed tomography includes patients aged 50–80 years old with 20 pack-year smoking history (9). Due to common risk factors and the high prevalence of chronic obstructive pulmonary disease (COPD) in the patient population of interest, some patients are unable to tolerate a pulmonary lobectomy due to impaired pulmonary function. Thorough assessment of pulmonary reserve can be accomplished with pulmonary function testing in the majority of cases. In patient with borderline results further assesment can be performed using quantitative V/Q scanning and cardiopulmonary exercise testing amongst others (10).

Regardless of the planned type of parenchymal surgical resection, there are three surgical approaches to consider—open thoracotomy, video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS). Recently, there has been a shift toward minimally invasive surgical options, with RATS rapidly gaining popularity and becoming the most common type of surgical approach due to inherent benefits with a three-dimensional view, magnification, tremor filtration, wristed instruments and others, despite incremental cost and lack of tactile feedback with a steep learning curve (11).

Of note, previous reviews have explored the evolution of extent of the resection and clinical implications of the recent key randomized controlled trials (12,13). In our review, we aim to offer a comprehensive analysis including not only the extent of resection, but also the surgical approach with a discussion of surgical adjuncts and cost analysis.

Objective

We conducted a literature analysis to better understand the indications and nuances of the current state of anatomical lung resection in the treatment of early-stage lung cancer with a focus on the role of sublobar resection. Additionally, we aim to explore the optimal surgical strategy with discussion of open and minimally invasive techniques. We present this article in accordance with the Narrative Review reporting checklist (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-30/rc).

Methods

Our study serves as an expert narrative review of the landmark papers and recent literature pertaining to the surgical treatments of early-stage lung cancer (Table 1). Articles to include in this review were identified using the PubMed, Medline, and Cochrane library from the date of inception to March 1, 2025. Article titles including “Non-Small Cell Lung Cancer”, “Lobectomy”, “Sublobar resection”, and “Segmentectomy” were evaluated for inclusion in the review. Exclusion criteria encompassed studies that were not published in English and case-reports. Relevant references in the articles were also assessed for inclusion. Eighty papers were screened and ultimately 43 were included. After consensus of both authors, results of selected studies are summarized below.

Surgical approaches for early-stage NSCLC

Extent of resection: lobectomy, segmentectomy, and wedge resections

Although surgery has been universally accepted as a gold standard in the management of early-stage lung cancer, there is no consensus on the extent of resection, ranging from wedge resection to lobectomy for small peripheral lung cancer. Lobectomy as a standard of care has been established by the Lung Cancer Study Group since 1995 (4). This was a randomized control trial including 247 patients with T1N0 NSCLC, defined at the time as tumor less than 3 cm in size with no lymph node involvement. The interventions were lobectomy versus sublobar resection, which included both segmentectomy and wedge resections with over 2 cm margins. The randomization process was quite rigorous, including decisions after thorough intraoperative assessment of the extent of disease by a surgeon. Although post-operative complications were comparable, sublobar resections had three times higher locoregional recurrence, which remained statistically significant when stratified by pathology. One criticism of this study is the high dropout rate, as out of the 771 registered patients, 495 were excluded for various reasons, including benign or non-adenocarcinoma histology and advanced disease, precluding sublobar resection. This accounts for 2/3 of participants and reduces the reliability of findings. However, this can partially be attributed to a limited preoperative workup, as plain radiographs alone prior to proceeding with surgery was an accepted practice at the time of the study. Advanced CT imaging was required only if there was suspicion of advanced or metastatic disease. Nevertheless, sublobar resections should have been more clearly delineated between segmentectomies and wedge resections as important oncologic implications arise.

Numerous retrospective studies challenged this practice in the late 2000s, especially when the United States Preventative Service Task Force recommended annual screening for high-risk individuals leading to earlier diagnosis of NSCLC (9). One of the first was a report by Schuchert et al., including 246 lobectomies and 182 segmentectomies from 2002–2006 for tumors less than 2 cm (T1_a-bN0) (14). There was no difference between complications or 30-day mortality. Overall, recurrence rates were similar between segmentectomy and lobectomy groups (17.6% vs. 16.7%). Notably, there was a smaller margin among patients with recurrence of only 12.8 mm versus 18.6 mm in patients without recurrence. The recurrence rates in patients with a margin:tumor size ratio of less than 1 were significantly higher (25.0% vs. 6.2%). Interestingly, segmentectomies compared to lobectomies were associated with shorter operative times and estimated blood loss, a finding that was later put into question by other studies.

More retrospective studies were presented, suggesting no difference in recurrence rate or mortality with segmentectomy for T1_a-bN0 NSCLC, prompting a systematic review and meta-analysis by Righi et al. (15,16). Data from eleven papers was pooled with a total of 3,074 lobectomies and 2,278 segmentectomies, excluding studies with wedge resections. Again, the hazard ratio and mean survival time was comparable, but there was a trend toward higher post-operative air leaks in the segmentectomy arm.

To investigate further, three randomized control trials were conducted recently (6,7,17). The JCOG0802/WJOG4607L was a non-inferiority trial, conducted in Japan from 2009–2014 and enrolled 1,106 patients with T1_a-bN0 tumors in the outer third of the lung, randomizing patients into lobectomy or segmentectomy (Table 2) (17). Segmentectomy had a strict definition of no more than 1–2 segments, with exclusion of the middle lobe. Post-operative complications were similar, but segmentectomies tended to have higher rates of air leaks. Although local recurrence rates were higher with segmentectomy (11% vs. 5%), the OS at the 5-year follow up was better (94.3% vs. 91.1%). Postoperative pulmonary function tests were superior in the segmentectomy group with a forced expiratory volume in one second (FEV₁) difference of 2.7% and 3.5% in 6 months and 1 year, respectively. Of note, an inclusion criterion was consolidation to tumor ratio over 0.5 with predominance of adenocarcinoma. This study has demonstrated astonishingly high OS in both groups of lung cancer and many authors question the generalizability of these findings to the typical practice (7). Post-hoc analysis on this patient cohort, revealed higher rates of locoregional recurrence with male sex [odds ratio (OR) 2.1], margins smaller than tumor size (OR 2.7), and pure solid morphology (OR 3.2) (8). Furthermore, a post-hoc analysis was performed to further investigate differences in survival, specifically looking at pure solid NSCLC, which are associated with a worse prognosis (18). Five-year OS in the segmentectomy group was improved with age >70 years (85.6% vs. 77.1%) and male sex (92.1% vs. 80.5%). In the lobectomy group, both age >70 years and male sex were associated with higher non-lung cancer related deaths, suggesting lower overall tolerance for the higher degree of resection. As highlighted by Potter et al., Western population have higher rates of solid nodules with more aggressive biology as opposed to the part-solid and ground glass opacity tumors heavily prevalent in this study (19). This has created controversy in the global application of the findings, making further trials with different patient populations vital.

Next, DRKS00004897 trial enrolled 108 patients from 2013–2016 in Germany, Austria, and Switzerland with T1_a-bN0 NSCLC (6). At the 5-year follow-up, OS in lobectomy and segmentectomy groups were 86% and 78% respectively, but were deemed non-inferior. As opposed to the previous trial, there was no statistical difference between locoregional or distant recurrence, although smaller size of the study has significantly reduced its power.

The CALGB 140503 trial randomized 697 patients from 2007–2017 in United States, Canada, and Australia with T1_a-bN0 NSCLC into lobectomy and sublobar resection (7). Randomization occurred intraoperatively with stratification by the tumor size, histology and smoking status. The decision of segmentectomy versus wedge resection in the sublobar group was left up to individual surgeons as well as surgical approach, open vs. minimally invasive. Notably, majority of the procedures in the trial were wedge resections (59.1%). No significant difference was demonstrated in 5-year recurrence free, disease free, or OS rates. Similarly to previous findings, sublobar resections provided better parenchymal preservation, with 2% superior FEV₁ results 6 months following surgery when compared to lobectomy. An important trend demonstrated by this study was the decreased 30-day (0.6% vs. 1.1%) and 90-day mortality (1.2% vs. 1.7%) in the sublobar resection group, although this was not statistically significant. Post-hoc analysis was completed to stratify data within sublobar resection into segmentectomy and wedge resection, showing no difference in 5-year OS (81.9% vs. 79.7%), overall recurrence rates despite inherent margin differences (31.5% vs. 31.2%), and post-operative FEV₁ (−3% vs. −5%) (20). Authors further emphasize the importance of adhering to the strict inclusion criteria when considering the extent of resection, as 6.4% of patients had intra-operative positive hilar or mediastinal nodes that would preclude a sublobar resection. Despite establishment of non-inferiority of sublobar resection with some evidence suggesting improved outcomes, this conclusion is nuanced due to the complexities of the pulmonary anatomy and technical aspects of the resections. While comparing results of different studies, the lobe location and number of segments removed must be taken into account, but these protocols are hard to define as they vary amongst surgeons.

Following the publication of the three landmark randomized trials, a French nationwide retrospective propensity score matching study was done comparing 1,604 segmentectomies and 14,786 lobectomies for tumors <2 cm between 2014 and 2016 (21). Post-operative complications were significantly less prevalent in the segmentectomy arm (27% vs. 34%) with no difference in peri-operative mortality. This further supports the non-inferiority of sublobar resection in different population outside of the countries included in the above randomized trials.

Wong et al. conducted a retrospective analysis using the National Cancer Database from 2004–2020, including a total of 28,460 lobectomies vs. 2,783 segmentectomies for T1_a-bN0 tumors (22). In this study, group size clearly demonstrates surgeons’ preference for lobectomies. An unsurprising finding in the study was an inferior lymph nodes yield in the segmentectomy group (7 vs. 10.5 nodes). Segmentectomies were stratified into “small lobes” (right upper and middle lobe) and “large lobes” (right lower, left upper, and left lower lobes) based on number of anatomical segments. Both small and large lobe segmentectomies had lower rates of major morbidity, defined as prolonged (>14 days) post-operative stay and 30-day mortality, which suggest superiority of the parenchymal sparing approach regardless of tumor location.

Some studies included wedge resection as part of the sublobar group, but the variability of such approach should caution thoracic surgeons from standardizing this approach. Krantz et al. attempted to create a consensus document with guidelines, including >2 cm margins and sampling of >3 N2 lymph node stations (23). Lymphatic drainage of the lungs is complex, following peribronchial and visceral intersegmental pleural pathways. Peripheral tumors that are more likely to be treated with a wedge resection are associated with higher prevalence of intersegmental pathway of lymphatic drainage (24). Thus, despite lymph node yield being lower with anatomic segmental resection, it may provide a more oncologically appropriate resection.

Patient reported outcomes following surgery

Since one of the advantages of sublobar resections is lesser extent of resection and thus parenchyma sparing nature of the procedure, it is important to evaluate the clinical implications of this as it relates to patient reported outcomes including symptoms (pain, cough, dyspnea, etc.), functional status (activity, work, mood, etc.), and overall quality of life.

Stamatis et al. conducted a prospective randomized trial including 108 patients in Germany, Austria, and Switzerland to better understand complication and quality of life outcomes for segmentectomy vs. lobectomy in early-stage lung cancer, including VATS and open cases (25). Complications and 90-day morbidity were similar, but differences arose when using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-LC13) scale for quality of life (26). There were expected worsening physical function, dyspnea, and fatigue at discharge for both groups. However, patients with a segmentectomy had quicker recovery to baseline at several time points following discharge. Final assessment at 12 months showed that while the segmentectomy arm largely returned to baseline, patients with lobectomy had persistent dyspnea, fatigue, physical and cognitive impairment. The difference was statistically significant for all categories.

Dai et al. assessed patient outcomes in a cohort of 110 patients who underwent minimally invasive segmentectomy vs. lobectomy in China with eligibility criteria mirroring the randomized controlled trial mentioned previously (27). Patients were surveyed using modified MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) (28). Symptoms assessed were cough, dyspnea, pain, fatigue, and sleep disturbance. There were no significant differences in severity of symptoms and functional impairments during both, hospitalization and 4 weeks following discharge.

Jiang et al. assessed this further by developing and validating their own post-operative quality of life scale (29). This scale was applied to consecutive patients from 2019–2021 at a single institution in China who underwent VATS sublobar resection or lobectomy. Although there were no significant differences in survey results immediately after surgery, postoperative quality of life was better in the sublobar group at both 3 and 6 months following surgery, specifically in the respiratory symptom domain.

Based on the current literature, segmentectomies tend to result in improved overall quality of life outcomes after the initial perioperative period. Nevertheless, global application of this data should be done with caution, as different assessment tools and cultural differences likely created bias.

Adjuncts to segmentectomy

Although data supports segmentectomies as the preferred resection for T1_a-bN0 NSCLC, this approach is technically challenging with up to 40% conversion rate to lobectomy (30). Near-infrared fluorescence mapping can be used as an adjunct in minimally invasive resections for identification of an intersegmental plane by systemic injection of indocyanine green (ICG) following ligation of bronchus and associated vessels (31). Mehta et al. conducted a prospective 53-patient cohort trial with comparison of thoracic surgeon predicted versus ICG delineated intersegmental plane (32). They found that the plane differed in 74.2% cases with ICG providing greater tumor margins in 61.2% of cases. With subsequent expansion of this study to 190 patients and subgroup analysis using three-time frames, the difference in margins diminished showing that ICG may be a useful tool for thoracic surgeons early in their careers (33).

Another adjunct to assist in segmentectomies is preoperative three-dimensional (3D) reconstruction. The DRIVATS study was a randomized controlled trial conducted from 2019–2023 including peripheral pulmonary noduled measuring less than 2 cm (34). A total of 191 patients were randomized into preoperative standard CT and 3D reconstruction, showing no difference in operative time or postoperative complications. However, combining 3D mapping and ICG in the robotic approach for a prospective cohort trial showed a 9% conversion rate from segmentectomy to lobectomy, lower than reported in literature (30). In conclusion, adjuncts for identifying the intersegmental plane may assist in improved margins for novice surgeons and decrease conversion rates of segmentectomy to lobectomy, but more studies are required to better assess the clinical and financial outcomes.

Surgical approach: thoracotomy, VATS, and RATS

In studies assessing extent of resection, decision on the surgical approach, either open thoracotomy or minimally invasive strategy (VATS or RATS) was universally deferred to the operating surgeon. One of the first papers to compare these approaches was done by Kent et al., querying the State Inpatient Database of 8 states from 2008–2010 for lobectomies and segmentectomies (Table 3) (35). Propensity-matched analysis was performed on 33,095 patients, including 20,238 thoracotomies, 12,427 VATS, and 430 RATS. Even in the early days of robotic surgery in thoracic space, the rates of robotic approach steadily increased from 0.2% to 3.4% from 2008 to 2010. Compared to open thoracotomy, RATS had significantly lower mortality (0.2% vs. 2.0%), length of stay (5.9 vs. 8.2 days), and overall complication rates (43.8% vs. 54.1%). No statistical differences were noted between VATS and RATS, likely owing to the limited number of robotic procedures in the analysis.

Subsequently, a series of studies using the Premier Healthcare Database analyzed the outcomes of these different approaches for lobectomies (Table 3). In the paper by Oh et al., authors focused on the 2011–2015 time frame, including 11,425 open thoracotomy, 9,360 VATS, and 2,994 RATS procedures (36). Authors demonstrated a steadily decreased rate of open thoracotomies by 11.5% by the end of the study, predominantly due to increased adoption of the robotic technology. After propensity-score matching of open and RATS cases, RATS was noted to have longer operating room (OR) times by 40 minutes, but lower post-operative complication (34.6% vs. 43.2%) and length of stay (7 vs. 8.9 days). When comparing VATS and RATS, robotic procedures demonstrated longer OR times by 28 minutes, but lower post-operative complications (34.1% vs. 37.6%). Specifically, post-operative bleeding, myocardial infarction, and conversion to open rates were higher in VATS. This data was further analyzed by Reddy et al. with subgroup analysis with high-volume surgeons performing >20 lobectomies annually, yielding similar conclusions for longer OR times but improved complication rates in the robotic group (37).

Nguyen et al. used the database from 2008–2015 to stratify minimally invasive approaches into early [2008–2012] and late [2013–2015] groups to account for the learning curve associated with robotic surgery (38). VATS conversion to open rate remained stable at ~10% and inferior to RATS (5–6%) in both groups. The time in OR and cost was higher in the RATS group, but was slightly improved in the late period with differences of 30 to 18 min and $1,328 to $1,279, respectively. Although there were no statistical differences in outcomes in the early period, RATS had lower in hospital and 30-day complications (38.9% vs. 44.3%) in the late group. Furthermore, subgroup analysis of high-volume hospitals performing greater than 25 lobectomies annually demonstrated shorter or similar OR times and no difference in cost, suggesting that operative efficiency with higher volumes negate the previously seen time and cost effect.

As more data were added to the Premier Healthcare Database, Alvarado et al. set out to reevaluate minimally invasive lobectomies from 2009 to 2019, including 43,192 VATS and 19,506 RATS cases (39). The frequency of RATS increased from 4.1% to 60.9% through the continuum of the study. VATS had higher rates of post-operative bleeding (8.9% vs. 6.9%), although rates of transfusion were comparable. Despite having similar mortality, OR times and length of stay, RATS was still more expensive ($90,593 vs. $72,733).

Kent et al. conducted the PORTaL study with retrospective analysis of open and minimally invasive lobectomies in 21 institutions for stage IA–IIIA lung cancer in 2013–2019 (40,41). Unlike the other studies, this study looked into recurrence and long-term outcomes, especially as it relates to clinical stage. Minimally invasive techniques were superior to open thoracotomy in terms of complications and length of stay; however, VATS had the worst OS (open 84%, VATS 74%, RATS 81%) and recurrence rates (open 16.5%, VATS 19.2%, RATS 15.9%) despite similar patient and tumor characteristics. Conversion rates remain higher in VATS when stratified by tumor stage and year of procedure, with RATS conversion rate decreasing throughout the study and less affected by the tumor stage.

Role of RATS segmentectomy

Recently, analysis of the National Cancer Databases from 2010–2017 showed increased rates of robotic segmentectomies from 13.3% to 33.4%, with preferential selection of older patients with more comorbidities (42). Echavvaria et al. performed a retrospective analysis of 251 consecutive robotics lobectomies and segmentectomies performed by one surgeon in 2010–2013, yielding 208 lobectomies and 43 segmentectomies (43). Although preoperative pulmonary function tests were worse in patients undergoing segmentectomies, they had diminished impact on both FEV₁ and diffusion capacity of carbon monoxide (DLCO) values as compared to lobectomies, consistent with previous studies (44). There were no differences in conversion rates and intra-operative complications, but segmentectomies had higher overall post-operative complications. Such, the rate of pneumothorax requiring chest tube re-insertion (10.3% vs. 1.9%) and empyema (16.3% vs. 1.0%) were higher. Also, segmentectomies had prolonged operative times (258 vs. 207.5 min). However, this data has a significant selection bias due to its retrospective nature.

Financial implications of the robotic approach

An important remaining discussion is the financial implications of robotic surgery, especially with studies showing increased cost. Abbas et al. conducted a prospective study including robotic surgery at Temple University in 2015 (45). Amongst all specialties, robotic thoracic surgery performed in the inpatient setting had the highest net margin, defined as percentage of revenue after subtraction of all direct and indirect costs. As mentioned previously, analysis of hospitals with >25 annual RATS or VATS cases by Nguyen at al showed no difference in total hospital cost within both the 2008–2012 ($23,784 vs. $22,599) and 2013–2015 ($21,315 vs. $21,103) periods. Furthermore, Kneuertz et al. compared cost between operative approaches for lobectomies done in 2012 to 2017 using the STS General Thoracic Surgery Database (46). Propensity-adjusted analysis of total direct hospital cost yielded similar results for RATS and VATS ($17,223 vs. $17,260). Thus, although initially more expensive than the VATS, robotic approach for segmentectomies and lobectomies may be financially comparable as experience and volume increases.

Conclusions

Randomized control trials comparing lobectomies and sublobar resections using any surgical approach showed equivalent or improved long-term outcomes in the management of small peripheral pulmonary nodules of less than 2 cm (T1_a-b) with the sublobar resections. However, sublobar resections had no clear definition for resection extent, with one study including both segmentectomy and wedge resection that have inherent variability. The robotic approach appears to have improved outcomes for anatomic lung resection in lobectomies as surgeons become more comfortable with the technology, but the data on the impact of robotic technology for pulmonary segmentectomies is still lacking. Synthesis of the evidence favors sublobar resection, preferably anatomic segmentectomy for early-stage peripheral T1_a-bN0 tumors. Nevertheless, segmentectomy should not be considered universally equivalent procedure to the lobectomy and should be approached with caution outside of experienced centers. Additionally, an important factor to consider is the higher proportion of open and VATS approaches in the earlier retrospective studies, limiting thorough evaluation of RATS at the time. Ultimately, further investigation into the nuances of surgical management of early-stage lung cancer and best practices of surgical access technology should continue.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Taryne A. Imai) for the series “Revolutionizing Lung Cancer Care with Technological Advancements” published in Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-30/rc

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-30/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-30/coif). The series “Revolutionizing Lung Cancer Care with Technological Advancements” was commissioned by the editorial office without any funding or sponsorship. R.V.P. reports consulting fees from Enterra Medical and Ideology Health, and stock ownership from RomTech. He also serves as executive board member of Eastern Cardiothoracic Surgical Society and Surgical Data Science Committee member of SAGES. R.V.P. also received travel support from Intuitive Surgical Inc., Zimmer Biomet and Atricure, and payment for expert testimony from Steptoe and Johnson attorneys at law and KY Bar Association. The authors have no other 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.

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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