Feasibility of endoscopic response evaluation after induction chemotherapy for determining treatment strategies in esophageal cancer: a post hoc analysis of the CROC trial

Chikatoshi Katada; Tetsuji Yokoyama; Akinori Watanabe; Yasuo Hamamoto; Ayumu Hosokawa; Takashi Kojima; Hiroki Hara; Takako Yoshii; Hirofumi Fujii; Hironori Yamaguchi; Takako Eguchi Nakajima; Naoki Izawa; Takayuki Ando; Motoo Nomura; Keishi Yamashita; Shogo Kawakami; Hiromichi Ishiyama; Yusuke Inoue; Yasutoshi Sakamoto; Hideki Ishikawa; Manabu Muto; Makoto Tahara; Wasaburo Koizumi

doi:10.1007/s10388-025-01169-w

Feasibility of endoscopic response evaluation after induction chemotherapy for determining treatment strategies in esophageal cancer: a post hoc analysis of the CROC trial

Esophagus. 2026 Jan;23(1):120-130. doi: 10.1007/s10388-025-01169-w. Epub 2025 Nov 25.

Authors

Chikatoshi Katada¹, Tetsuji Yokoyama², Akinori Watanabe³, Yasuo Hamamoto⁴, Ayumu Hosokawa⁵, Takashi Kojima⁶, Hiroki Hara⁷, Takako Yoshii⁷, Hirofumi Fujii⁸, Hironori Yamaguchi⁸, Takako Eguchi Nakajima⁹, Naoki Izawa¹⁰, Takayuki Ando¹¹, Motoo Nomura¹², Keishi Yamashita¹³, Shogo Kawakami¹⁴, Hiromichi Ishiyama¹⁴, Yusuke Inoue¹⁵, Yasutoshi Sakamoto¹⁶, Hideki Ishikawa¹⁷, Manabu Muto¹², Makoto Tahara¹⁸, Wasaburo Koizumi³

Affiliations

¹ Department of Medical Oncology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo, Kyoto, 606-8507, Japan. ckatada@kuhp.kyoto-u.ac.jp.
² Department of Health Promotion, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0197, Japan.
³ Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, 252-0374, Japan.
⁴ Department of Medical Oncology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
⁵ Department of Clinical Oncology, University of Miyazaki Hospital, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
⁶ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.
⁷ Department of Gastroenterology, Saitama Cancer Center, 780 Komuro, Ina, Kitaadachi-gun, Saitama, 362-0806, Japan.
⁸ Department of Clinical Oncology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
⁹ Department of Early Clinical Development, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo, Kyoto, 606-8507, Japan.
¹⁰ Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.
¹¹ Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
¹² Department of Medical Oncology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo, Kyoto, 606-8507, Japan.
¹³ Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, 252-0374, Japan.
¹⁴ Department of Radiation Oncology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, 252-0374, Japan.
¹⁵ Department of Diagnostic Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, 252-0374, Japan.
¹⁶ Translational Research Support Office, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.
¹⁷ Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
¹⁸ Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

PMID: 41288834
DOI: 10.1007/s10388-025-01169-w

Abstract

Background: The CROC trial assessed a response-guided approach using endoscopic criteria to identify candidates for definitive chemoradiotherapy (dCRT) as an alternative to surgery for resectable thoracic esophageal squamous cell carcinoma (ESCC). Precise evaluation of treatment response following induction chemotherapy is essential for determining curative strategies.

Methods: This post hoc analysis of the CROC trial investigated the interobserver concordance of endoscopic response evaluation and its clinical implications. Eighty-seven patients with resectable thoracic ESCC underwent three cycles of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Endoscopic responses were centrally reviewed by three expert oncologists and categorized as remarkable response (RR), limited partial response, or poor response. Patients were classified as having definitive RR, definitive non-RR, or uncertain response based on reviewer agreement.

Results: A comprehensive consensus was achieved, with 51.7% (45/87) and 31.0% (27/87) of patients categorized as definitive RR and definitive non-RR, respectively, whereas 17.2% (15/87) were classified as uncertain response. Patients with definitive RR and uncertain response exhibited high complete response (CR) rates to dCRT at 89.7% (35/39) and 90.9% (10/11), respectively, whereas those with definitive non-RR demonstrated a lower CR rate of 25.0% (1/4). ¹⁸F-fluorodeoxyglucose positron emission tomography revealed a progressive decrease in maximum standardized uptake value in the RR and uncertain response groups compared with the non-RR group. Among the surgical cases with definitive RR, the positive predictive value for pathological findings was 83.3% (5/6).

Conclusions: High interobserver concordance supports standardizing endoscopic evaluation criteria. Furthermore, an uncertain response may indicate the suitability of dCRT because of favorable outcomes.

Keywords: CROC trial; Chemoradiotherapy; DCF; Esophageal cancer; Induction chemotherapy.

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Chemoradiotherapy / methods
Cisplatin / administration & dosage
Docetaxel / administration & dosage
Esophageal Neoplasms* / diagnostic imaging
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / pathology
Esophageal Neoplasms* / therapy
Esophageal Squamous Cell Carcinoma* / pathology
Esophagoscopy* / methods
Feasibility Studies
Female
Fluorouracil / administration & dosage
Humans
Induction Chemotherapy* / methods
Male
Middle Aged
Observer Variation
Treatment Outcome

Substances

Docetaxel
Cisplatin
Fluorouracil