Non-cancer-related deaths in patients with resectable locally advanced esophageal squamous cell carcinoma: A supplementary analysis of JCOG1109.
Authors: Hiroshi Imazeki, Ken Kato, Yoshinori Ito, Hiroyuki Daiko, Keisho Chin, Kazuo Koyanagi, Takashi Ogata, Hiroki Hara, Takeo Fujita, Tetsuya Abe, Fumitaka Endo, Shigeru Tsunoda, Atsushi Takeno, Yoshiaki Nagatani, Hisayuki Matsushita, Hiroshi Sato, Satoru Matsuda, Kota Kawabata, Ryunosuke Machida, Hiroya Takeuchi
Journal: Journal of Clinical Oncology (2025)

434 Background: Neoadjuvant docetaxel, cisplatin, and 5-FU (DCF) has become the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) in Japan, based on the result of JCOG1109. In this study, more non-cancer-related deaths were observed in the cisplatin, and 5-FU (CF) plus radiotherapy (CF-RT) arm compared to the CF and DCF arm. However, the details of these non-cancer-related deaths remain unclear. We aimed to evaluate the influence of neoadjuvant therapies on non-cancer-related deaths using the data from JCOG1109. Methods: We analyzed patients' characteristics, classification, time of onset, risk factors associated with onset, and cumulative incidences in patients with non-cancer-related deaths. Cumulative incidences of non-cancer-related deaths in each arm were estimated, considering cancer-related deaths as a competing risk. Risk factors were explored using multivariable Fine-Gray model with Firth penalization. Results: Among 601 enrolled patients, 164 in the CF arm, 169 in the DCF arm, and 173 in the CF-RT arm were completed the surgery. Of those, non-cancer-related deaths were observed in 19 (12%), 12 (7%), and 32 (18%) patients, respectively. Patient characteristics of non-cancer-related deaths in the CF/DCF/CF-RT arm were as follows: male, 89/92/88%; median age, 69/69/69 years old; ECOG PS 0, 89/100/97%; lower thoracic esophagus, 21/25/19%; previous history of ischemic disease of heart, 5/0/0%; brain, 0/0/0%; other malignancies, 5/8/0%; comorbidity of hypertension, 26/25/47%; COPD, 0/8/3%; thoracoscopic approach, 37/42/38%. The median follow-up time was 5.7 years (range, 0.3-10.4 years). The causes of non-cancer-related deaths in the CF/DCF/CF-RT arm were pulmonary, 4 (21%)/1 (8%)/10 (31%); cardiovascular, 1 (6%)/0/2 (6%); infectious, 2 (11%)/1 (8%)/3 (9%); other malignancy, 2 (11%)/3 (25%)/5 (16%); treatment-related, 0/1 (8%)/1 (3%), and the median time from surgery to onset of non-cancer-related death was 3.3/3.8/4.3 years, respectively. Cumulative incidences of non-cancer-related deaths after 3, 6, 9 years in the CF/DCF/CF-RT arm were 4.9/3.0/7.0%, 10.7/6.1/15.6%, 12.4/8.8/26.1%, respectively. In multivariable analyses, ≥ 65 years old (hazard ratio [HR]: 3.243, 95% confidential interval [CI]: 1.797–5.852, vs. &lt; 65 years old), ECOG PS 0 (HR: 3.579, 95% CI: 1.148–11.162, vs. PS 1), and serum CRP ≥ 1.0 mg/dl (HR: 2.238, 95% CI: 1.003–4.995, vs. &lt;1.0 mg/dl) were significantly associated with the onset of non-cancer-related deaths. Whereas the CF-RT arm was not significantly associated (HR: 1.600, 95% CI: 0.885–2.892, P = 0.12, vs. CF). Conclusions: The incidence of non-cancer-related deaths was relatively higher in the CF-RT arm, and pulmonary-related complications tended to be a particularly common cause of death.