Prognostic Analysis of Pathological Stage I Lung Adenocarcinoma Harboring Major EGFR Mutations

Shinkichi Takamori; Makoto Endo; Akira Hamada; Shuta Ohara; Shota Fukuda; Yasuaki Tomioka; Satoshi Takamori; Atsushi Osoegawa; Kotaro Nomura; Kosuke Fujino; Mao Yoshikawa; Ken Suzawa; Kazuhiko Shien; Kenichi Suda; Fumihiko Kinoshita; Kazuki Hayasaka; Hirotsugu Notsuda; Taichi Nagano; Kyoto Matsudo; Asato Hashinokuchi; Taichi Matsubara; Shinya Katsumata; Satoshi Shiono; Junichi Soh; Yasuhisa Ohde; Mototsugu Shimokawa

doi:10.1016/j.cllc.2024.12.011

Prognostic Analysis of Pathological Stage I Lung Adenocarcinoma Harboring Major EGFR Mutations

Clin Lung Cancer. 2024 Dec 26:S1525-7304(24)00284-5. doi: 10.1016/j.cllc.2024.12.011. Online ahead of print.

Authors

Shinkichi Takamori¹, Makoto Endo², Akira Hamada³, Shuta Ohara³, Shota Fukuda³, Yasuaki Tomioka⁴, Satoshi Takamori², Atsushi Osoegawa⁵, Kotaro Nomura⁶, Kosuke Fujino⁷, Mao Yoshikawa⁸, Ken Suzawa⁸, Kazuhiko Shien⁸, Kenichi Suda³, Fumihiko Kinoshita⁹, Kazuki Hayasaka¹⁰, Hirotsugu Notsuda¹⁰, Taichi Nagano¹¹, Kyoto Matsudo¹¹, Asato Hashinokuchi¹¹, Taichi Matsubara¹², Shinya Katsumata¹³, Satoshi Shiono¹⁴, Junichi Soh³, Yasuhisa Ohde¹³, Mototsugu Shimokawa¹⁵

Affiliations

¹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan. Electronic address: [email protected].
² Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
³ Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.
⁴ Division of Thoracic Surgery, Department of Surgery, Faculty of Medicine, Shimane University, Shimane, Japan; Department of Thoracic Surgery, Fukuyama City Hospital, Fukuyama, Japan.
⁵ Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan.
⁶ Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
⁷ Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁸ Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan.
⁹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
¹⁰ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
¹¹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹² Department of Thoracic Surgery, Kitakyushu Municipal Medical Center, Fukuoka, Japan.
¹³ Division of Thoracic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁴ Department of Surgery II, Faculty of Medicine, Yamagata University, Yamagata, Japan.
¹⁵ Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

PMID: 39824660
DOI: 10.1016/j.cllc.2024.12.011

Abstract

Background: While Epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LUAD) has favorable outcomes with targeted therapy, early-stage prognosis remains influenced by pathological factors and central nervous system (CNS) recurrence. The study aimed to clarify prognostic factors in pathological stage (pStage) I EGFR mutation-positive LUAD.

Methods: Between 2015 and 2018, 2,191 pStage I LUAD cases with known EGFR status (excluding EGFR testing after recurrence) who received anatomical resection were included from multiple institutions in Japan. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed.

Results: 1,073 (49.0%) cases harbored EGFR mutations, including 419 (19.1%) with 19del and 529 (24.1%) with L858R. In cases with major EGFR mutation (n = 948), multivariate analysis showed that the absence of noninvasive area (NIA) (hazard ratio [HR]: 1.778, 95% confidence interval [CI]: 1.174-2.692, P = .0065), pStage (IA2 vs. IA1, HR: 2.079, 95% CI: 1.129-3.827, P = .0345; IA3 vs. IA1, HR: 4.009, 95% CI: 2.088-7.696, P = .0001; IB vs. IA1, HR: 5.280, 95% CI: 2.871-9.709, P < .0001), and presence of lymphatic invasion (HR: 1.855, 95% CI: 1.103-3.119, P = .0197) were independent predictors of shorter DFS, and only advanced pStage was an independent predictor of CNS recurrence (relative risk for pStage IA3 or more: 9.729, P < .0001).

Conclusion: In EGFR mutation-positive pStage I LUAD, those without NIA, with higher pStage and lymphatic invasion were independent predictive factors for DFS, and pStage ≥ IA3 was an independent predictor of CNS recurrence.

Keywords: Central nervous system; Epidermal growth factor receptor; Lung cancer; Prognosis; Surgery.