Satoru Okada1,2, Shunta Ishihara3, Masashi Yanada4, Tsunehiro Ii5, Satoshi Ikebe6, Chiaki Nakazono1, Yasuo Ueshima3, Kenji Kameyama1,5, Hiroaki Tsunezuka7, Motohiro Nishimura8, Shinya Ito9, Kunihiko Terauchi10, Kazuhiro Ito11, Daishiro Kato12, Hiroyuki Izumi13, Hirofumi Suzuki14, Yoshiaki Matsuura14, Masanori Shimomura1, Tatsuo Furuya1, Masayoshi Inoue1
1Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;
2Department of Thoracic Surgery, Kyoto Chubu Medical Center, Nantan, Japan;
3Department of General Thoracic Surgery, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan;
4Department of General Thoracic Surgery, Japanese Red Cross Kyoto Daiini Hospital, Kyoto, Japan;
5Department of General Thoracic Surgery, Ayabe City Hospital, Ayabe, Japan;
6Department of Thoracic Surgery, Fukuchiyama City Hospital, Fukuchiyama, Japan;
7Department of Thoracic Surgery, Otsu City Hospital, Otsu, Japan;
8Department of Thoracic Surgery, Saiseikai Suita Hospital, Suita, Japan;
9Department of Thoracic Surgery, Uji-Tokushukai Medical Center, Uji, Japan;
10Department of Chest Surgery, Nara City Hospital, Nara, Japan;
11Department of Thoracic Surgery, Kyoto Yamashiro Medical Center, Kizugawa, Japan;
12Department of Thoracic Surgery, Saiseikai Shiga Hospital, Ritto, Japan;
13Department of Thoracic Surgery, Matsushita Memorial Hospital, Moriguchi, Japan;
14Department of Thoracic Surgery, Osaka General Hospital of West Japan Railway Company, Osaka, Japan
Correspondence to: Satoru Okada, MD, PhD. Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan; Department of Thoracic Surgery, Kyoto Chubu Medical Center, Nantan, Japan. Email: s-okada@koto.kpu-m.ac.jp.
Background: Tumor size was proposed as a T descriptor for stage I thymic epithelial tumors (TETs) in the forthcoming 9th edition tumor-node-metastasis (TNM) classification. This study clarified the prognostic impact and optimal tumor size cutoff for advanced TETs.
Methods: A multicenter retrospective study comprising 100 patients with TETs requiring combined resection of adjacent organs or pleural dissemination was conducted from January 2000 to April 2024. Survival was analyzed using the Kaplan-Meier curve (log-rank test). Multivariable analyses using the Cox proportional hazards model evaluated the significance of tumor size. The variables included age, sex, histology, R status, pathological TNM stage (9th edition), and tumor size. The C-index, including various tumor size cutoff values in 0.5 cm increments, was calculated to compare the predictive performance among the models.
Results: Sixty thymomas, 40 thymic carcinomas, or thymic neuroendocrine tumors were analyzed. The median tumor size was 5.5 cm. Nineteen patients had myasthenia gravis. Complete tumor resection was performed in 73 patients. The pathological TNM stages were I, II, III, and IV in 28, 31, 19, and 22 patients, respectively. During a median 47-month observation, 30 progressions/relapses were recorded. Five- and 10-year progression-free survival (PFS) rates were 61.1% and 54.1%, respectively. In 72 patients with 9th-edition TNM stages II–IV (Masaoka III–IV), the C-index for PFS was highest in the model with a cutoff of 5 cm (C-index =0.712). Patients with tumors >5 cm had significantly poorer PFS than the others (5-year PFS, 39.1% vs. 78.8%, P=0.01). In 47 patients with stage II–IV tumor (R0), the C-index was the highest in the model with a cutoff of 5 cm for freedom from recurrence (FFR) (C-index =0.707). FFR was significantly poorer in patients with tumors >5 cm (5-year FFR, 35.3% vs. 84.6%, P=0.03). Multivariable analysis demonstrated that a large tumor size (>5 cm) was an independent, poor prognosticator for FFR (hazard ratio 4.64, 95% confidence interval: 1.20–31.0) in stage II–IV (R0).
Conclusions: Tumor size is a poor prognosticator in surgically resected advanced TETs. The optimal cutoff for discriminating prognosis in stage II–IV TETs was 5 cm, which was compatible with the proposed cutoff for stage I TET.
Keywords: Thymic epithelial tumor; tumor size; recurrence; prognostic factor
