Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study

Hidehito Horinouchi; Haruyasu Murakami; Hideyuki Harada; Tomotaka Sobue; Tomohiro Kato; Shinji Atagi; Toshiyuki Kozuki; Takaaki Tokito; Satoshi Oizumi; Masahiro Seike; Kadoaki Ohashi; Tadashi Mio; Takashi Sone; Chikako Iwao; Takeshi Iwane; Ryo Koto; Masahiro Tsuboi

doi:10.1016/j.lungcan.2024.108027

Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study

Lung Cancer. 2024 Nov 14:199:108027. doi: 10.1016/j.lungcan.2024.108027. Online ahead of print.

Authors

Hidehito Horinouchi¹, Haruyasu Murakami², Hideyuki Harada³, Tomotaka Sobue⁴, Tomohiro Kato⁵, Shinji Atagi⁶, Toshiyuki Kozuki⁷, Takaaki Tokito⁸, Satoshi Oizumi⁹, Masahiro Seike¹⁰, Kadoaki Ohashi¹¹, Tadashi Mio¹², Takashi Sone¹³, Chikako Iwao¹⁴, Takeshi Iwane¹⁴, Ryo Koto¹⁴, Masahiro Tsuboi¹⁵

Affiliations

¹ Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
² Department of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
³ Division of Radiation Therapy, Shizuoka Cancer Center, Shizuoka, Japan.
⁴ Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁵ Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center, Hyogo, Japan.
⁶ Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan.
⁷ Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
⁸ Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital, Fukuoka, Japan.
⁹ Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Hokkaido, Japan.
¹⁰ Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital, Tokyo, Japan.
¹¹ Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
¹² Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
¹³ Department of Respiratory Medicine, Kanazawa University Hospital, Ishikawa, Japan.
¹⁴ Department of Medical, AstraZeneca K.K., Osaka, Japan.
¹⁵ Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan. Electronic address: mtsuboi@east.ncc.go.jp.

PMID: 39708388
DOI: 10.1016/j.lungcan.2024.108027

Abstract

Objectives: 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.

Materials and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Adjuvant therapy; Chemoradiotherapy; Neoadjuvant therapy; Non-small cell lung cancer; Observational study; Retrospective study; Surgery.