Recommendation-adherent systematic lymph node sampling is not associated with increased complication rates in non-small cell lung cancer surgery—combined cardiothoracic center experience

Introduction

Lung cancer is the leading cause of cancer mortality worldwide (1). Surgery for lung cancer includes harvesting of lymph nodes to establish accurate cancer staging and can be carried out to variable extents ranging from more limited or selective lymph node sampling to full lymph node dissection with all adjacent mediastinal fatty tissue removed (2). During lung cancer surgery lymph nodes can be resected from several stations, specifically stations 2–11 (3). Limited sampling (LS) includes harvesting lymph nodes only from stations of immediate proximity to the tumor or only including lymph nodes that are in the lobe, whereas systematic lymph nodal sampling aims to collect a specific number of lymph nodes covering predefined stations that are not in the immediate surgical area of the lobe that is affected by a malignant tumor (4). The American College of Surgeons (ACS) Commission on Cancer’s current recommendation updated the sampling recommendation from harvesting 10 or more lymph nodes to three or more N2 stations with at least one N1 station included (5,6).

When considering the extent of lymph node harvesting, recommendation-adherent systematic sampling (RA) has been associated with less local recurrence than LS (7). More extensive lymph node harvesting may improve overall survival but has been associated with a mildly higher risk of perioperative complications (8,9). Furthermore, some studies have reported lower complication rates and faster recovery with a more conservative approach to lymph node harvesting (8,10). Although in large-scale multicenter study found no association between more extensive lymph node harvesting and complication rates, data from smaller centers are limited (11). Our aim was to determine whether more extensive lymph node harvesting is safe in a low- to medium-volume combined cardiothoracic center.

The purpose of our study was to investigate the relationship between the extent of lymphadenectomy and incidence of perioperative complications. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0209/rc).

Materials and methods

Oulu University Hospital is a tertiary care hospital covering a large geographical area in Northern Finland with a referral population of 750,000 people. The design of our study was a retrospective observational single-center cohort study. All patients who were operated on to treat non-small cell lung cancer (NSCLC) in our institution between 2010 and 2023 were included in this study and all underwent anatomical lobectomy. Exclusion criteria were age under 18 years, other diagnosis than NSCLC, sub-lobar resections and any combined or extended resections beyond lobectomy. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. We have received approval from Oulu University Hospital Ethics Board (case number 5/2019), and approval from Oulu University Ethics Board (EETTMK 81/2008). Due to the study’s retrospective nature, informed consent from patients was waived. The research reported was conducted in an ethical and responsible manner and is in full compliance with all relevant codes of experimentation and legislation.

A total of 521 patients were diagnosed with NSCLC and treated with lobectomy during the study period. The patients were classified in three groups based on the extent of lymph node harvesting according to the final histopathological report: no nodal sampling (NS), LS and RA. The RA group was defined as resection of three N2 lymph node stations and one N1 hilar station and a total of ≥10 examined lymph nodes, consistent with the current and prior ACS recommendations (5,6). The LS group included the patients that underwent nodal harvesting of the stations in proximity to the involved lobe and whose total amount of successfully sampled lymph nodes did not meet the definition of RA. The NS group was defined as resections with only harvesting of N1 lymph nodes included in the removed lobe without harvesting any mediastinal N2 nodes. A total of 89 patients were allocated into the NS group, 313 into the LS group, and 119 into the RA group. The primary outcome was the incidence of any complication. Secondary outcomes were Clavien-Dindo grade ≥ III complication, the comprehensive complication index (CCI) (12), overall complication rate, chylothorax, recurrent laryngeal nerve injury, upstaging due to lymph node involvement, hospital stay, 30- and 90-day mortality. Patient information was collected from electronic patient reports.

Open pulmonary lobectomy was performed via anterolateral or posterolateral thoracotomy. The video-assisted approach included a four-port setting including a fifth intercostal space utility incision for pathological specimen removal. Robotic-assisted surgery employed the da Vinci Xi system (Intuitive Surgical, Sunnyvale, CA, USA) using the four-arm approach in addition to an assistant AirSeal port (ConMed, Largo, FL, USA). The extent of lymph node sampling was ultimately decided by the operating surgeons. LigaSure Maryland-device (Medtronic, Minneapolis, MN, USA) was available for all operations as an option for electrocautery. All surgeries were performed with a team of two surgeons and if the operating surgeon was in training, the assisting surgeon was selected among more experienced consultants.

Statistical analysis was performed using IBM SPSS statistics software version 29.0.1.0. Descriptive statistics were used to summarize patient characteristics across three groups. The Chi-squared test was used for categorical variables. Continuous variables were compared using one-way analysis of variance (ANOVA) or Kruskal-Wallis test depending on the data distribution. For postoperative complications two regression models were constructed including lymph node assessment, surgical technique, age, sex, smoking status, Charlson Comorbidity Index and histology. A binary logistic regression model was analyzed in univariate and multivariate manners with the following covariates: nodal sampling, surgical technique, cStage, pStage, histology and age. There were no missing data in the key variables.

Results

Demographics are presented in Table 1. Overall demographics were statistically comparable, but more advanced clinical and pathological stage was observed in those patients that underwent more extensive lymph node sampling. Thoracotomy rates were higher with more extensive lymph node sampling (Table 1). RA was performed for 22.8% and LS for 60.1% of patients.

Regarding overall complications, there was no statistical difference between the groups (38.2% for NS, 39.6% for LS and 35.3% for RA, P=0.71, Table 2). Rates of Clavien-Dindo grade III and above complications were similar between the groups (NS 12.4%, LS 11.2% and RA 17.6%, P=0.20). CCI median 0, interquartile range (IQR) 0–20.9 in all groups, P=0.89. Mean CCI values were similar (Table 2). The 30- and 90-day mortality was not statistically different between the groups (P=0.39, Table 2). The RA group was associated with a higher amount of recurrent nerve injuries (1.7% compared to 0 in other groups, P=0.03). One of these patients had lymph node metastasis growing into the recurrent nerve and another had metastasis in node 6. The extent of lymph node sampling technique was not found to be a statistically significant risk factor for complications in the univariate or multivariate regression models (Table 3).

Discussion

The American College of Surgeons Commission on Cancer’s recommendation-adherent systematic sampling in conjunction with lobectomy for NSCLC was not associated with higher complication risk compared to LS or NS of N2 stations in our study population.

This study has some limitations such as a single-center and retrospective design with a relatively small dataset. Although, this is compensated by full access to electronic patient records facilitating availability of complete clinical data on the operatively treated lung cancer population of Northern Finland. Undocumented factors affecting surgeons’ decisions on the extent of lymph node harvesting is a further study limitation. Therefore, it is possible that in more technically difficult cases or when encountering hostile pleural adhesions, the surgeon chose more LS with the intention of reducing the risk of sampling-related complications, which may have introduced selection bias. At least one of the two surgeons participating in the operation was always a consultant with wide experience on lung cancer surgery and surgical energy devices were widely available which limits confounding factors from skill or instrumentation-based factors. Our center is the sole tertiary care center in Northern Finland, and our data set can be considered as a population-based study covering half of Finland’s land area. As such, the study center is responsible for or at least involved in almost all lung cancer treatment decisions in our coverage area.

Despite previous studies suggesting a potentially increased rate of complications with more extensive lymph node sampling (8,10), our results suggest that the ACS recommendation-adherent systematic sampling does not lead to higher complication rates compared to a more LS or even resection without any N2 lymph nodal assessment. The original hypothesis was that more extensive surgical preparation would lead to increased complications. This was not observed in our study as the incidence of chylothorax, phrenic nerve and recurrent laryngeal nerve injuries were low; under 1.7% in all groups and comparable to or lower than previous studies (7). Two recurrent nerve injuries were found in the RA group, but both cases were found to have metastases in lymph nodes close to the recurrent nerve.

RA should be the golden standard, but it is still performed infrequently (15,16). Our study population had a higher rate of RA when compared with some previous studies (22.8% vs. 12–20%) (5), although the overall remained relatively low. Our study included only lobectomies, which may partly explain these differences. Clinical stage III was identified in 69 patients, but only 13 patients received neoadjuvant therapy. In Finland, neoadjuvant therapies have gained popularity in recent years following the introduction of programmed death-ligand 1 (PD-L1)-targeted therapies, which likely explains the low rate of neoadjuvant treatment in our cohort. Nodal upstaging was found in both LS and RA groups, which highlights the known need for lymph node harvesting in lung cancer surgery for accurate pre- and post-operative staging. Differences in operative techniques were observed between the groups. Because all surgeons practiced as cardiothoracic surgeons and were therefore more familiar with open surgery, this may explain the higher thoracotomy rate in the RA group. In our study, the proportion of nodal upstaging was 6.9% (LS) and 9.4% (RA), comparable to results reported in other studies (7.0% to 16.3%) (10,15). Our study included a relatively high proportion of patients with only N1 sampling. In earlier years, nodal sampling may have been performed inadequately, which may partly explain these findings. In addition, lymph node harvesting was sometimes omitted in patients, who were unfit for or declined adjuvant therapy. When considering quality of surgery, the amount of lymph nodes dissected is usually regarded as a surrogate of surgical oncological quality. Thus, efforts to increase the amount of dissected lymph nodes is encouraged (17), although the total lymph node yield itself does not comprehensively describe the extent of the dissection. The American College of Surgeons Commission on Cancer’s sampling recommendations with a focus on the number stations dissected might provide a more accurate descriptor of the extent of the nodal harvesting. Our study does not support the hypothesis that complication rates are increased with more extensive nodal harvesting.

Conclusions

Our conclusion is that the ACS recommendation-adherent systematic lymph node harvesting with a combined focus on nodal stations and total lymph node yield in lobectomy is not associated with increased complication rates in lung cancer surgery when compared to a more LS.

Acknowledgments

We would like to express gratitude for all the funding we have received.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0209/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0209/prf

Funding: This work was supported by Personal grant for research, Väinö and Laina Kivi Foundation; personal grant for research, Foundation of the Finnish Anti-Tuberculosis Association (to A.P.), Finnish State Research Funding (to O.H.), Finnish State Research Funding, Finnish Cancer Foundation (to J.H.K.), Finnish State Research Funding, funding from the Thelma Mäkikyrö Foundation (to F.Y.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1-0209/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 research reported was conducted in an ethical and responsible manner and is in full compliance with all relevant codes of experimentation and legislation. We have received approval from Oulu University Hospital Ethics Board (case number 5/2019), and approval from Oulu University Ethics Board (EETTMK 81/2008). Due to the study’s retrospective nature, informed consent from patients 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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