Impact of lymphadenectomy extent on immunotherapy efficacy in postresectional recurred non-small cell lung cancer: a multi-institutional retrospective cohort study

Author:

Deng Hongsheng1,Zhou Juan2,Chen Hualin3,Cai Xiuyu4,Zhong Ran1,Li Feng1,Cheng Bo1,Li Caichen1,Jia Qingzhu5,Zhou Caicun2,Petersen René H.6,Rocco Gaetano7,Brunelli Alex8,Ng Calvin S.H.9,D’Amico Thomas A.10,Su Chunxia2,He Jianxing1,Liang Wenhua1,Zhu Bo5,

Affiliation:

1. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China

2. Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China

3. Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

4. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

5. Institute of Cancer, Xinqiao Hospital, The Army Medical University, Chongqing, China

6. Department of Cardiothoracic Surgery, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark

7. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA

8. Department of Thoracic Surgery, St. James's University Hospital, Leeds, UK

9. Department of Surgery, Division of Cardiothoracic Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China

10. Department of Surgery, Division of Thoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA

Abstract

Background: Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, the authors aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel ‘immunotherapy-driven’ LN dissection strategy. Materials and methods: The authors conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification. Results: A total of 144 patients were included, of whom 59 had a DLN count less than or equal to 16 (median, IQR: 11, 7–13); 66 had a DLN count greater than 16 (median, IQR: 23, 19–29). With a median follow-up time of 14.3 months (95% CI: 11.0–17.6), the overall median progression-free survival (PFS) was 7.9 (95% CI: 4.1–11.7) months, 11.7 (95% CI: 7.9–15.6) months in the combination therapy subgroup, and 4.8 (95% CI: 3.1–6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count less than or equal to 16 is associated with an improved PFS in all cohorts [primary cohort: HR=0.26 (95% CI: 0.07–0.89), P=0.03]; [validation cohort: HR=0.46 (95% CI: 0.22–0.96), P=0.04]; [entire cohort: HR=0.53 (95% CI: 0.32–0.89), P=0.02]. The prognostic benefit of DLN count less than or equal to 16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065–0.845, P=0.027). Conclusions: An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in the immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine,Surgery

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