Sublobar resection for non-small cell lung cancer: a narrative review of recent new investigations

Introduction

Despite tremendous advances in public health, such as smoking cessation and lung cancer screening, along with other advances such as immunotherapy and minimally invasive surgical techniques, lung cancer continues to be the number one cause of cancer-related death in the United States (1). With an aging, comorbid population, one area of recent research interest has been the role of sublobar resection for early non-small cell lung cancer (NSCLC). Several recent studies have demonstrated equivalent outcomes for sublobar resection versus standard lobectomy for early-stage NSCLC, challenging the previous standard of care (2-5).

For the past few decades, the results from the landmark 1995 Lung Cancer Study Group have driven the standard of care for early-stage lung cancer. These investigators compared the role of sublobar resection to lobectomy for early-stage T1N0 peripheral NSCLC. In a prospective multi-institutional randomized control trial of 247 patients undergoing either lobectomy or sublobar resection (either nonanatomic wedge resection or segmentectomy), the authors compared the 5-year survival rate, locoregional and distant recurrence, and late pulmonary function. When comparing sublobar resection to lobectomy, investigators noted a 75% increase in recurrence rate, a 30% increase in overall death rate, and a 50% increase in death with cancer. The authors were unable to demonstrate a durable difference in post-operative pulmonary function between the two groups, although many patients did not have follow-up data, making conclusions unclear. Overall, the Lung Cancer Study Group concluded that the benefits of limited pulmonary resection did not outweigh the increased risk of recurrence and mortality associated with sublobar resection; therefore, lobectomy became the standard of care for all early-stage peripheral NSCLC (6).

Interest in sublobar resection for NSCLC has been rekindled in recent years for several reasons. One major contributing factor has been over a decade of experience with lung cancer screening using chest computed tomography (CT) scans, a recommendation made by the United States Preventive Services Task Force (USPSTF) in 2013. Lung cancer screening, in combination with liberal use of high-resolution CT scans for other purposes such as emergency department evaluation, has led to earlier detection of lung masses at smaller sizes (7). In one review by Bagga et al., incidental lung nodules were noted in 13% of all chest CT angiograms and 24% of all chest CT scans (8). Improvements in imaging technology, identification of smaller lesions, and improvements in minimally invasive surgical technique prompted several surgeons to re-investigate sublobar resection with two major landmark studies, the Japanese Clinical Oncology Group (JCOG) trial and the North American Cancer and Leukemia Group B (CALGB) trial (2,3). Given the ever-changing landscape of lung cancer care, we present this narrative review on the current state of sublobar resection for early-stage NSCLC, discuss practical clinical applications, and future implications of the current ground-breaking research to date. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-25-5/rc).

Methods

A PubMed search was used, including keywords “lung cancer”, “sublobar”, “lobectomy”, “segmentectomy”, and “lung cancer screening”. Studies were initially screened based on the abstract and title, specifically as it relates to the topic. This led to a primary review of three randomized controlled trials and three meta-analyses studying the outcomes of sublobar resection for early NSCLC, paying specific attention to large, multi-center trials. Additional studies, including meta-analyses, randomized controlled trials, prospective observation studies, and retrospective cohort studies, were reviewed using PubMed and referenced as necessary in this review. The review was limited to studies in English and published after 1950. Please see Table 1 for additional details regarding literature search criteria.

Role of sublobar resection

Two recent studies have been impactful in shifting the body of evidence regarding sublobar resection. The JCOG trial published its results of a randomized controlled trial comparing lobectomy to sublobar resection in 2022. This was followed shortly after by a publication by Altorki of the North American CALGB sublobar versus lobectomy trial in 2023 (2,3). Both investigators found similar results with some differences in patient selection and operations utilized.

Both recent studies focused on individuals with early-stage NSCLC, specifically T1a-bN0, which equates to a tumor size of less than 2 cm. The lesion was also required to be in the periphery of the lung, defined as the outer one-third. For the CALBG trial, additional patient-specific factors included an ECOG performance status of 0 to 2, no malignant disease in the past 3 years except nonmelanoma skin cancer, superficial bladder cancer, and carcinoma in situ of the cervix. These patients were required to have not undergone any chemotherapy or radiation therapy nor had any evidence of locally advanced or metastatic disease. In the operating room, an additional eligibility criterion was confirmation of negative nodal spread by frozen section (3). The JCOG trial noted many similar inclusion criteria, as well as exclusion criteria notable for uncontrolled diabetes mellitus, uncontrolled hypertension, or severe heart disease (2). These highly selective parameters led to an exclusive study population that allowed for greater control of patient-specific factors that could influence outcomes outside of surgical approach, enabling more direct comparison of technique.

In the JCOG trial, 1,106 patients from over 70 institutions in Japan were randomized to either lobectomy (n=554) or segmentectomy (n=552). With the hypothesis that segmentectomy was not inferior to lobectomy, the primary outcome was overall survival, with important secondary endpoints of postoperative respiratory function, local recurrence, and adverse events. With a median follow-up time of 7.3 years, the 5-year survival rate was 94.3% for segmentectomy versus 91.1% for lobectomy. Five-year relapse-free survival was 88.0% for segmentectomy versus 87.9% for lobectomy, which was not a statistically significant difference. Regarding postoperative respiratory function, the difference between the two groups of reduction of median forced expiratory volume in 1 second (FEV₁) was 3.5%, in favor of segmentectomy (P<0.0001), but did not reach the predetermined threshold for clinical significance of 10%. For adverse events, intraoperative complications were 2% for segmentectomy versus 1% for lobectomy, with postoperative complications of 27% for segmentectomy compared to 26% for lobectomy. Overall, the results from the JCOG trial concluded that segmentectomy was superior to lobectomy in terms of overall survival while remaining non-inferior in postoperative respiratory function for this patient population (2).

Similar outcomes were noted in the North American CALGB trial, which included 697 patients randomly assigned to sublobar resection (either wedge resection or segmentectomy) or lobectomy, again evaluating whether the sublobar resection was not inferior to the standard of care surgical modality of a lobectomy with a primary objective of disease-free survival. Three hundred and forty patients were assigned to sublobar resection, and 357 patients were assigned to lobectomy. Five-year disease-free survival was noted at 63.6% for the sublobar group compared to 64.1% for the lobectomy cohort. Disease recurrence overall was 30.4% for the sublobar group and 29.3% for the lobectomy cohort. The magnitude of reduction of both FEV₁ and forced vital capacity (FVC) was greater for the lobectomy group compared to the sublobar group by 2 percentage points in both categories (3).

STA550/1-1 is a smaller but significant recently published multicenter randomized controlled trial. This study included 108 patients with small (less than 2 cm) NSCLC randomized to either lobectomy or segmentectomy. Similar to the JCOG trial, no patients underwent non-anatomic wedge resection. The STA550/1-1 investigators found no statistically significant difference in overall 5-year survival or disease-free survival (4).

Various systematic reviews and meta-analyses have been performed evaluating sublobar review compared to lobectomy. Meldola et al. noted similar overall survival and disease-free survival when comparing sublobar resection to lobectomy; however, recurrence and post-operative pulmonary function are difficult to determine due to differences in study parameters, most notably the type of sublobar resection performed (5). In the meta-analysis by Lu et al., there was no statistical difference in overall survival and disease-free survival comparing sublobar resection to lobectomy in stage I NSCLC, although the authors note that differences in the type of sublobar resection as a key limitation (9). Data presented in a systematic review by Merritt et al. would support sublobar resection for high-risk surgical patients, given equivalent oncologic outcomes with the benefit of preserving lung parenchyma compared to lobectomy (10).

Discussion

With broadening indications for lung cancer screening and ongoing advancements in CT technology and navigational bronchoscopy, it is likely that early smaller-sized NSCLC will become increasingly identified, thus, more potential candidates for sublobar resection will emerge. The optimal treatment strategy for these patients remains a matter of some debate. Anatomic lobectomy remains an oncologically sound option. Available data suggests that pulmonary function, as measured by FEV₁ and FVC, may be decreased to a greater degree in comparison to sublobar resection (3). Additional research on differences in pulmonary function, perhaps including quality of life indicators or the 6-minute walk test, has been advocated by some authors (3). Limiting the amount of pulmonary parenchymal resection may benefit patients with diminished preoperative pulmonary function who would not otherwise tolerate a lobectomy. As a result, some stage 1 NSCLC patients can be offered sublobar resection as an alternative to radiation, which may have worse overall survival and disease-free survival versus sublobar resection (11).

A second ongoing area of debate is segmentectomy versus nonanatomic wedge resection in this patient population. A criticism of 2 out of the 3 referenced randomized controlled trials on the subject of lobectomy versus sublobar resection has been the lack of distinction between anatomic and nonanatomic resection in the “sublobar” arm of these studies. Improved resection of lymphatic drainage associated with a segmentectomy may be more oncologically sound. In a recent post-hoc analysis of CALBG 140503 data, there were no reported statistically significant differences in disease-free survival, overall survival, or rate of locoregional recurrence between segmentectomy and wedge resection, though segmentectomy was associated with a larger surgical margin. The authors noted that the study was not powered or intended to demonstrate differences between these groups (12). Several retrospective studies have demonstrated better parenchymal margin, better lymph node harvest, and lower locoregional recurrence with anatomic segmentectomy (13-16). Further study is needed to better understand whether there is an oncologic benefit of segmentectomy compared with nonanatomic wedge resection.

There is significant enthusiasm for sublobar resection in the wake of these clinical trials. However, there are several pertinent details worthy of consideration before offering sublobar resection for early-stage NSCLC. Surgeons should note the inclusion and exclusion criteria for each study prior to generalizing the outcomes of these studies to the entire population of early-stage NSCLC. Both studies required a small tumor size, 2 cm or less, but size was not the only tumor characteristic in the inclusion criteria of these studies. Eligibility was also limited to peripheral lesions located in the outer one-third of the lung. CALGB specifically excluded patient with pure ground-glass opacities, while JCOG required a consolidation-to-tumor ratio of greater than 0.5. Patient factors were also important considerations. JCOG excluded patients with prior ipsilateral thoracotomy, severe emphysema, pulmonary fibrosis, and uncontrolled comorbidities such as diabetes and hypertension. The specific inclusion criteria set in the CALGB and JCOG studies assisted in providing more direct comparison related to surgical technique and avoid bias related to patient-specific factors rather than developing criteria for sublobar resection or lobectomy. Current clinical practice suggests sublobar resection as ideal operative management in high-risk patients with future studies looking to further elucidate this management strategy (17,18). Surgeons should carefully evaluate patient and tumor characteristics to ensure applicability of these trial data prior to offering sublobar resection for early NSCLC.

With respect to staging, the CALGB trial only randomized patients after intraoperative frozen sections of one major hilar and two mediastinal stations were negative for cancer. The JCOG trial sent nodes for frozen section selectively if they appeared macroscopically concerning for metastasis. Since both studies confirmed N0 status intraoperatively prior to proceeding with sublobar resection, surgeons offering sublobar resection for NSCLC should proceed similarly. Frozen section, while not necessarily mandatory, should be available for rapid microscopic diagnosis. This requires a supportive Pathology department with appropriate expertise and availability. Surgeons and patients should be prepared to proceed with lobectomy if nodal disease is discovered intraoperatively; however, a recent retrospective study from the group at Memorial Sloan Kettering evaluating outcomes of occult node-positive disease in patients that underwent a segmentectomy for cT1N0M0 NSCLC on pathology had limited isolated recurrence and overall outcomes comparable to those patients that underwent lobectomy (19). This raises the question of benefit of lobectomy compared to segmentectomy and may further decrease the utility of intraoperative frozen section. Ultimately, further data are needed to address this aspect of nodal disease in the setting of T1 NSCLC.

Additionally, it is worth noting that the sublobar resection group in both studies had higher rates of local recurrence, though not statistically significant in the CALGB trial, but similar long-term survival. The segmentectomy arm of the JCOG study had more frequent re-resection or other additional interventions compared with lobectomy. These findings highlight the critical importance of follow-up and surveillance. Surgeons offering sublobar resection to this patient population must therefore be particularly attentive to appropriate surveillance and follow-up after treatment.

Conclusions

Two recent large randomized controlled trials suggest that sublobar resection for carefully selected early NSCLC patients offers equivalent oncologic efficacy compared to lobectomy, a potentially practice-changing finding. There is evidence of improved pulmonary function in the sublobar group, but the clinical significance of this difference is unclear. Appropriate patient selection is critical, and application of these data in clinical practice should be applied in a patient-specific manner. Further research is necessary to determine other potential clinical benefits of sublobar resection, including in the realm of quality of life after lesser surgery. Further study of outcomes differences between segmentectomy and nonanatomic wedge resection is necessary to fully elucidate optimal treatment of early NSCLC, along with ongoing efforts in lung cancer screening. Sublobar resection for NSCLC represents an exciting frontier in precision-based lung cancer care.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Gregory Trachiotis) for the series “Preoperative Planning and Assessment for VATS Lung Cancer Resection” published in Video-assisted Thoracoscopic Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-25-5/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-25-5/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-25-5/coif). The series “Preoperative Planning and Assessment for VATS Lung Cancer Resection” was commissioned by the editorial office without any funding or sponsorship. S.J.S. serves as the Honorary Editor-in-Chief of Video-assisted Thoracoscopic Surgery from October 2025 to September 2027. 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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