Safety and necessity of omitting mediastinal lymph node dissection in cN0/N1 non-small cell lung cancer after neoadjuvant immunotherapy

Yuheng Zhou ¹ Wenyu Zhai ¹ Weizhen Sun ¹ Yongping Han ² Zhichao Lin ³ Dihan Liu ³ Yan Zheng ⁴ Xiaojuan Luo ² Zerui Zhao ¹ Shoucheng Feng ¹ Yaobin Lin ^1* Hailin Tang ^1* Hao Long ^1*

• ¹ Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
• ² Yiyang Central Hospital, Yiyang, China
• ³ Jiangmen Central Hospital, Jiangmen, Guangdong, China
• ⁴ Henan Provincial Cancer Hospital, Zhengzhou, Henan Province, China

Background: Lymph nodes are crucial for perioperative immunotherapy but have to be completely resected in surgery. Trial evaluating the safety and necessity of omitting systemic mediastinal-lymph-node (mLN) dissection in non-small cell lung cancer (NSCLC) is still absent.Methods: cN0/N1 NSCLC patients who received neoadjuvant immunotherapy and radical surgery were retrospectively collected from three institutions. Restricted cubic spline regression and receiver operating characteristics curve were used to analyze the association between mLN dissection number and survival outcomes. Confounding factors between selective and systemic mLN dissection groups were adjusted by inverse probability treatment weighting (IPTW). Characteristics of memory CD8 + T cells in immunotherapy-treated mLN were identified by single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) data retrieved from GSE185206.Results: From 2019 to 2021, 131 neoadjuvant-treated cN0/N1 NSCLC patients were collected.The mLN clearance rate was 98.5% in the whole cohort and 100% in patients with radiologically-confirmed complete response. Resected lymph node counts were irrelevant with local recurrence, distant metastasis, or death. Compared with selective mLN dissection, systemic mLN dissection did not show any survival benefit but slightly higher postoperative recurrence risk in both unadjusted and IPTW-adjusted cohorts. scRNA/TCR-seq showed that stem-like exhausted CD8 + memory T cells were the progenitors of tumor-specific CD8 + T lymphocytes in primary tumor and were abundantly enriched in resected mLN.Conclusions: Omitting systemic mLN dissection was safe in cN0/N1 NSCLC patients who received neoadjuvant immunotherapy. Excessive mLN dissection may disrupt the repertoire of stem-like exhausted CD8 + memory T cells and consequently impair the efficacy of adjuvant immunotherapy.