Clinical N Staging Subclassification for Stage III-N2 NSCLC Patients Undergoing Trimodality Therapy: A Good Beginning Is Half the Battle

Junghee Lee ¹, Yun Soo Hong ², Jin Lee ³

¹Department of Thoracic and Cardiovascular Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
²Department of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Genetic Medicine, McKusick-Nathans Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
³Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; Center for Clinical Epidemiology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
⁴Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; Patient-Centered Outcomes Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
⁵Department of Thoracic and Cardiovascular Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
⁶Department of Thoracic and Cardiovascular Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea; Patient-Centered Outcomes Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
⁷Department of Epidemiology, School of Global Public Health, New York University, New York, New York.
⁸Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; Department of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Center for Clinical Epidemiology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea; Patient-Centered Outcomes Research Institute, Samsung Medical Center, Seoul, Republic of Korea.

⁰Department of Thoracic and Cardiovascular Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea; Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

The Annals of Thoracic Surgery +

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March 23, 2025

View abstract on PubMed

Summary

Subclassifying N2 nodal involvement in stage III non-small cell lung cancer (NSCLC) is crucial. The cN2b subclassification indicates a higher risk of recurrence and mortality compared to cN2a in patients undergoing trimodality therapy.

Area Of Science

Oncology
Thoracic Surgery
Pulmonary Medicine

Background

Stage III-N2 non-small cell lung cancer (NSCLC) necessitates precise nodal staging for optimal treatment planning.
Subclassification of N2 nodal involvement may refine prognostic assessment in NSCLC patients.

Purpose Of The Study

To evaluate the prognostic value of clinical N descriptor subclassification (cN2a vs. cN2b) in patients with stage III-N2 NSCLC undergoing trimodality therapy.
To determine if this subclassification predicts recurrence-free survival and overall survival.

Main Methods

Analysis of 899 consecutive stage III-N2 NSCLC patients from an institutional registry (2003-2019).
Patients underwent neoadjuvant concurrent chemoradiotherapy followed by surgery.
Clinical N2 was subclassified into cN2a and cN2b based on imaging and histopathology; survival outcomes were compared using competing risks and Cox proportional hazards models.

Main Results

56.0% of patients were classified as cN2a and 44.0% as cN2b.
The cN2b group showed significantly higher adjusted hazard ratios for recurrence (1.22) and mortality (1.43) compared to cN2a.
This increased risk was observed in both adenocarcinoma and squamous cell carcinoma subtypes.

Conclusions

The proposed clinical N subclassification (cN2a vs. cN2b) is a valuable predictor of prognosis in stage III-N2 NSCLC.
cN2b classification is associated with a higher risk of recurrence and mortality.
This stratification aids in decision-making for trimodality therapy in NSCLC.