Horinouchi Hidehito, Murakami Haruyasu, Harada Hideyuki, Sobue Tomotaka, Kato Tomohiro, Atagi Shinji, Kozuki Toshiyuki, Tokito Takaaki, Oizumi Satoshi, Seike Masahiro, Ohashi Kadoaki, Mio Tadashi, Sone Takashi, Iwao Chikako, Iwane Takeshi, Koto Ryo, Tsuboi Masahiro
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Lung Cancer. 2025 Jan;199:108027. doi: 10.1016/j.lungcan.2024.108027. Epub 2024 Nov 14.
There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method.
Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy-61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group-42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group-37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era.
关于IIIA-N2期非小细胞肺癌（NSCLC）的可切除性标准，目前尚未达成广泛共识。我们根据日本IIIA-N2期NSCLC的治疗方式，研究了患者特征、N2状态、治疗决策及临床结局。
2013年至2014年期间，日本IIIA-N2期NSCLC患者连续纳入SOLUTION研究。患者根据治疗方式分为三组（同步放化疗[CRT]、手术+围手术期治疗[新辅助和/或辅助治疗]、单纯手术）。对人口统计学特征、N2状态（数量和形态特征）、病理信息及治疗进行描述性分析。采用Kaplan-Meier法估计总生存期（OS）、无进展生存期（PFS）和无病生存期（DFS）。
在登记的227例患者中，133例接受了CRT，56例接受了手术+围手术期治疗，38例接受了单纯手术。133例CRT患者中，医生报告的不可切除原因如下：转移淋巴结数量多（70.7%）、结外浸润（25.0%）、手术耐受性差（19.0%）或其他原因（18.1%）。CRT在淋巴结呈浸润性表现的患者中更常进行（64.3%），并且是多站受累患者的主要治疗方式（离散型：60.0%；浸润型：80.4%）。CRT组、手术+围手术期治疗组和单纯手术组分别有50.4%、50.0%和36.8%的患者发生远处转移伴/不伴局部进展。三组的3年OS率和DFS/PFS率（中位值）如下：手术+围手术期治疗组-61.9%（未达到）和37.1%（22.4个月；DFS）；CRT组-42.2%（31.9个月）和26.8%（12.0个月；PFS）；单纯手术组-37.7%（26.5个月）和28.7%（12.6个月；DFS）。
本研究阐明了IIIA-N2期NSCLC患者在手术和非手术治疗方法选择上的真实世界决策规则。我们的标志性数据可为围手术期治疗时代使用免疫检查点抑制剂和驱动癌基因靶向治疗的治疗决策提供支持。
