Spirited discussion: lymph node count versus nodal station count

The quality of lymphadenectomy significantly influences long-term outcomes after the surgical management of early-stage non-small-cell lung cancer (NSCLC) [1]. Several current guidelines provide recommendations for adequate nodal examination in patients with NSCLC. Three mediastinal nodal stations are the minimum standard set by the National Comprehensive Cancer Network [2], and the Union for International Cancer Control advises the removal of 3 N1 and 3 mediastinal lymph nodes (LNs) [3]. Nonetheless, the extent of lymphadenectomy in patients with early-stage NSCLC remains a controversial topic. In recent years, researchers have increasingly focused on determining the optimal threshold for examined lymph node count (ELNC) due to the acknowledged significance of ELNC in early-stage NSCLC prognosis [4–6].

To further investigate the importance of the ELNC in patients with early-stage NSCLC, Zeng et al. [7] conducted an extensive analysis of surgeries for T1 NSCLC documented in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. The authors analysed N upstaging, long-term survival and mortality risk in patients with T1 NSCLC using different ELNC cut-off values [7]. They observed improved patient outcomes when the ELNC was ≥8, revealing associations with increased N upstaging, enhanced long-term survival, and reduced mortality from lung cancer, chronic obstructive pulmonary disease (COPD) and cardiac diseases [7].

Previous studies revealed similar associations between the ELNC of patients undergoing lung cancer surgery and N upstaging and improved survival [4, 5, 8]. In a population study analysing patients with resected NSCLC using a Chinese registry (n = 5706) and the Surveillance, Epidemiology, and End Results database (n = 38 806), higher ELNC was associated with improved overall survival in patients with N0 NSCLC. Furthermore, the examination of ≥16 lymph nodes was associated with a significant reduction in all-cause mortality among patients with N0 NSCLC in both registry cohorts [4]. Another multicentre study from China included 1205 patients with resected stage I–II NSCLC and demonstrated that examining at least 18 resected LNs or examining ≥6 LN stations could significantly reduce all-cause mortality [5]. Notably, both in Eastern and Western countries, there is an ongoing debate about the optimal ELNC in patients with T1 NSCLC.

Moreover, this study by Zeng et al. aligns with evolving considerations of the TNM staging system, highlighting the imperative for comprehensive categorization of LN metastatic involvement. The N-Descriptors Subcommittee of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee thoroughly examined diverse factors influencing the categorization of LN metastatic involvement in the context of developing the 9th edition TNM staging system [9]. N descriptor classification currently relies exclusively on anatomical criteria, encompassing the counting of LNs, LN stations, or LN zones, and a meticulous analysis has been conducted of the advantages and disadvantages associated with these methods [9]. The research conducted by Zeng et al. [7] adds valuable insights to this foundational data that will shape clinical decision-making and guide recommendations in forthcoming revisions of the TNM staging system.

While we commend the authors for their efforts in establishing a numerical standard for LN resection based on a large patient cohort (38 242 patients), a critical focus of this study lies in the correlation between ELNC and the potential reduction of mortality from COPD and cardiac diseases. The low incidence of COPD-related deaths (4.1%) and deaths from cardiac pathologies (5.1%) in the matched group raises concerns about interpretation of the results, as the risk of false positives and susceptibility to random statistical fluctuations is increased when small sample sizes are examined [10]. Given the extremely low death rates from COPD and cardiac diseases, distinguishing genuine effects from random variations might be particularly challenging. Interpreting these results with caution is advisable. Replicating these findings in independent studies and considering their clinical context are essential to confirm their validity and clinical relevance. Although the authors present interesting theoretical explanations for their observations, none have undergone validation.

Overall, the study by Zeng et al. adds more questions than it answers to what seems to be a never-ending debate of LN count versus nodal station count in patients with T1 NSCLC. Their establishment of a numerical standard using a large study cohort will likely be a helpful addition to these spirited discussions. Caution is advised, however, regarding their claims of reduced mortality risk from cardiac pathologies and COPD due to low-level evidence warranting additional validation and exploration of clinical implications.