Segmentectomy vs. lobectomy for occult N1 in non-small cell lung cancer—outcomes do not solely depend on surgical resection

Segmentectomy has become standard surgical treatment in non-small cell lung cancer (NSCLC) with tumor size ≤2 cm since Cancer and Leukemia Group B (CALGB) 140503 (1) and Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L (2) revealed oncological feasibilities of sublobar resection and segmentectomy, respectively. However, the indications for segmentectomy remain controversial when unexpected nodal metastasis is found intraoperatively or postoperatively. Patients who are diagnosed with N1 disease pathologically (pN1) after undergoing surgery for clinically N0 disease (cN0) are classified as having “occult N1” disease. The optimal extent of resection (segmentectomy vs. lobectomy) for occult N1 cases is a major clinical dilemma.

Present study focused on the clinical issues that thoracic surgeons face more in the segmentectomy era. It is reasonable to recognize that completion lobectomy improves the prognosis of occult N1 disease compared to segmentectomy. Two champion studies have left little suggestion on this issue. The CALGB 140503 study excluded cases in which metastatic lymph nodes were intraoperatively detected, whereas the JCOG 0802/WJOG 4607L study randomized cases without nodal metastasis suspicion, and lobectomy was mandated if nodal disease was proven intraoperatively.

Abdallat et al. compared the outcomes of cN0 but pN1 NSCLC patients treated with segmentectomy (n=30) with those of patients treated with lobectomy (n=155) (3). They concluded that segmentectomy was associated with similar overall survival (OS) and locoregional recurrence-free survival (LRFS) as lobectomy using propensity score weighting analysis. Specifically, the 5-year OS rates after weighting were 79.69% and 66.22% in the segmentectomy and lobectomy groups, respectively (P=0.40), showing no significant difference. Study cohorts were extracted from a large database consisting of approximately 4,000 patients.

Similar previous studies found no statistical difference in survival between segmentectomy and lobectomy groups (4-11). Several studies compared the outcomes between segmentectomy and lobectomy for NSCLC with unsuspected N1–2 disease (4-7,9,10). They employed the adjusting analysis using propensity matching or inverse probability weight analysis, and concluded no significant differences in OS, recurrence-free survival (RFS), or recurrence rate. Nomori et al. reviewed 15 cases of cT1N0M0 segmentectomy. Ten patients were additionally treated with completion lobectomy due to occult N1–2, and five cases were treated by segmentectomy without completion lobectomy regardless of N1–2 metastasis. Two of the five segmentectomy cases experienced recurrence but 10 patients with completion lobectomy showed no residual metastases in specimens resected additionally by completion lobectomy. They concluded that radical segmentectomy with extensive hilar/mediastinal lymph node dissection and sufficient surgical margins was sufficient for local control in patients with pN1–2 NSCLC (12). No significant difference was indicated even in cohorts consisting of occult N2 disease only and including wedge resection as sublobar resection (9). The results of these studies, including the present study, are highlighted in Table 1.

Acceptance of segmentectomy in occult nodal disease can be seen in current clinical trial; a current ongoing randomized phase III study comparing prognosis (OS and RFS) between anatomical segmentectomy and lobectomy in cStageIA3 pure-solid (tumor diameter >2 and ≤3 cm) NSCLC does not mandate completion lobectomy if nodal metastasis is intraoperatively proven in segmentectomy cohort (13).

In addition to the curability of segmentectomy itself, the present study (3) includes several potential reasons for the good outcomes of segmentectomy.

First, the tumor size and standard uptake value (SUV) were smaller in the segmentectomy group. In addition, nodal metastasis was occult pathological metastasis proven “post-operatively”. Metastasis in the lymph nodes was not detected intraoperatively, suggesting that the metastatic lesion was small, similar to oligometastasis in the lymph nodes. These patients can be treated by complete tumor resection.

Second, the prolonged OS and RFS were partially due to adjuvant treatment. Adjuvant therapy with conventional cytotoxic agents, tyrosine kinase inhibitors, or immune checkpoint inhibitors can improve prognosis (14-17). Approximately 67% of patients received adjuvant treatment. In previous studies, patients treated by segmentectomy received adjuvant therapies at a similar frequency to those who were treated by lobectomy.

Third, as mentioned by the authors, neither distant metastasis nor spread through air spaces (STAS) was evaluated. Pioneering research on this topic has reported distant metastases after segmentectomy (12). The existence of STAS can affect the incidence of occult N1 and oncological outcome (18-21).

In conclusion, while the findings of Abdallat et al. are reassuring for patients who undergo segmentectomy and are subsequently upstaged to pN1, we must not misunderstand that segmentectomy solely assures the optimal prognosis in all occult pN1 cases. In cN0 patients with a high risk of pN1–2 [e.g., predominantly solid appearance on computed tomography (CT), high SUV on positron emission tomography (PET)-CT, suspicion of pleural invasion, or swollen lymph nodes], intraoperative lymph node examination is required. In node-positive cases, conversion to lobectomy may not be necessary; however, ensuring sufficient resection margins, performing systematic nodal dissection, and genetic status exploration should be considered. In cases of occult nodal disease, tighter follow-up and adjuvant therapy are warranted for a better prognosis.

Acknowledgments

We would like to thank Editage (www.editage.jp) for English language editing.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-47/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-2025-1-47/coif). The authors have no conflicts of interest to declare.

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