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Outcomes of patients with esophageal squamous cell carcinoma who achieved a pathological complete response in the primary lesion by neoadjuvant treatment: a Japanese nationwide cohort study

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Abstract

Background

Minimal data was reported regarding the characteristics, risks of lymph node metastasis, and prognostic factors in esophageal cancer patients who achieved remarkable response in the primary lesion to neoadjuvant treatment (NAT).

Methods

This study evaluated the nationwide data of esophageal squamous cell carcinoma (ESCC) patients who underwent surgery following NAT in Japan. Of 4484 patients, 300 (6.7%) had ypT0 following NAT and curative esophagectomy. Factors associated with lymph node metastasis and prognosis were analyzed.

Results

Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) were administered in 260 (86.2%) and 40 (13.8%) patients, respectively. Pathologically, 72 (24.0%) had lymph node metastasis (residual nodal disease; RND), and pretherapeutic lymph node metastasis was the independent risk factor for RND (odd ratio [OR]: 3.21; 95% confidence interval [CI]: 1.44–8.20; P = 0.008). The 5-year overall and relapse-free survivals were significantly longer in patients with pathological complete response (pCR) than in those with RND (both P < 0.001). Pretherapeutic cT3 or T4a tumors (hazard ratio [HR]: 1.71; 95% CI: 1.02–2.88; P = 0.043), RND (HR: 3.30; 95% CI: 1.98–5.50; P < 0.001), and operative blood loss (Liter, HR: 1.53; 95% CI: 1.07–2.19; P = 0.021) were independent risk factors affecting relapse-free survival in multivariable analysis.

Conclusions

Of patients with ypT0 after NAT, 24.0% had RND, and pretherapeutic lymph node metastasis was the risk factor. In addition, pretherapeutic cT3, or T4a tumors, RND, and operative blood loss were the poor prognosticators in patients with ypT0 after NAT.

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Acknowledgements

The authors sincerely appreciate all participating investigators for their valuable assistance with data collection: Matsumoto Sohei (Nara Medical University); Katsushi Takebayashi (Shiga University); Tomokazu Kakishita (Shikoku Cancer Center); Youichi Kumagai (Saitama Medical University); Takahisa Suzuki (Kure Medical Center and Chugoku Cancer Center); Yasuyuki Kawachi (Nagaoka Chuo General Hospital); Yasuhiro Tsubosa (Shizuoka Cancer Center Hospital); Naoya Yoshida (Kumamoto University); Yusuke Sato (Akita University); Noriaki Sadanaga (Saiseikai Fukuoka General Hospital); Tomoyuki Matsunaga (Tottori University); Masahiko Koike (Nagoya University); Kentaro Kishi (Osaka Police Hospital); Fumihiko Kato (International University of Health and Welfare); Hiroaki Nagano (Yamaguchi University); Shirou Kuwabara (Niigata City General Hospital); Takahiro Yoshida (Tokushima University); Katsunori Nishikawa (The Jikei University); Koichi Okamoto (Kanazawa University); Yoshihiko Kawaguchi (University of Yamanashi); Shinsuke Sato (Shizuoka General Hospital); Hironori Ohdaira (International University of Health and Welfare Hospital); Koji Kono (Fukushima Medical University); Akihiro Hoshino (Tokyo Medical and Dental University); Yousuke Kubota (Hiraka General Hospital); Sanshiro Kawata (Hamamatsu University); Takayoshi Kishino (Kagawa University); Yoshihiro Tanaka (Gifu University); Shuji Takiguchi (Nagoya City University Hospital); Fumihiro Yoshimura (Fukuoka University); Takeo Bamba (Niigata Cancer Center Hospital); Akio Kaito (Tsuchiura Kyodo General Hospital); Shinichi Kadoya (Ishikawa Prefectural Central Hospital); Yoshinori Hosoya (Jichi Medical University); Takuji Sato (Kochi Health Sciences Center); Makoto Kobayashi (Hakodate Goryoukaku Hospital); Kentaro Iwaki (Oita Red Cross Hospital); Gousuke Takiguchi (Kobe University); Motohisa Hagiwara (Nihonkai General Hospital); Koichi Ono (Obihiro Kosei Hospital); Ryuichiro Ohashi (Kagawa Prefecural Central Hospital); Shunichi Okushiba (Tonan Hospital); Takashi Nomura (Yamagata Prefectural Central Hospital); Yoichi Hamai (Hiroshima University); Eigo Otsuji (Kyoto Prefectural University); Koichi Demura (JCHO Osaka Hospital); Koichi Ogawa (University of Tsukuba); Yusuke Umeki (Fujita Health University); Dai Otsubo (Hyogo Cancer Center); Naoki Mori (Kurume University); Takashi Fukuda (Saitama Cancer Center); Tomohisa Egawa (Saiseikai Yokohamashi Tobu Hospital); Ken Sasaki (Kagoshima University); Shota Maruyama (Hachinohe City Hospital); Hisayuki Matsushita (Tochigi Cancer Center); Syoji Takagi (Okayama Red Cross Hospital); Takuo Takehana (Saku Central Hospital Advanced Care Center); Kotaro Yamashita (Osaka University); Tatsusi Suwa (Kashiwa Kousei General Hospital); Takushi Yasuda (Kindai University); Sang-Woong LEE (Osaka Medical and Pharmaceutical University); Nobutoshi Hagiwara (Nippon Medical School); Hirokazu Noshiro (Saga University); Shigeru Tsunoda (Kyoto University Hospital); Yukinori Kamio (Yamagata University); Hiroshi Ichikawa (Niigata University); Tomotaka Shibata (Oita University); Masaru Morita (Kyushu Cancer Center); Masanobu Nakajima (Dokkyo Medical University); Kazuhiro Noma (Okayama University); Shinya Mikami (St.Marianna University); Yusuke Taniyama (Tohoku University); Kiminari Naoshima (Iwate Prefectural Chubu Hospital); Ryo Maeyama (JCHO Kyushu Hospital); Yoshiro Aoki (Hiroshima City Asa Citizens Hospital); Hiroshi Miyata (Osaka International Cancer institute); Tomoki Yamatsuji (Kawasaki Medical School); Yoshihiro Ota (Tokyo Medical Unversity Hospital); Yuji Akiyama (Iwate Medical University); Kazuo Koyanagi (Tokai University); Yuji Kikuchi (Tokyo Dental College Ichikawa General Hospital); Kazuhiko Yamada (National Center for Global Health and Medicine); and Takeo Fujita (National Cancer Center Hospital East). The authors wish to acknowledge Kumiko Motooka and Sanae Oikawa, staff members of the study team, for their help in collecting patient data.

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Author notes

  1. Akihiko Okamura, Jun Okui, and Satoru Matsuda contributed equally to this article.

Authors and Affiliations

  1. Department of Esophageal Surgery, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Akihiko Okamura & Masayuki Watanabe

  2. Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan

    Jun Okui

  3. Department of Surgery, School of Medicine, Keio University, Tokyo, Japan

    Jun Okui, Satoru Matsuda, Hirofumi Kawakubo & Yuko Kitagawa

  4. Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan

    Ryo Takemura

  5. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan

    Yoshihiro Kakeji

  6. Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan

    Koji Kono

  7. Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan

    Hiroya Takeuchi

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  1. Akihiko Okamura
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Corresponding author

Correspondence to Masayuki Watanabe.

Ethics declarations

Ethical statement

The Ethics Committee of all participating esophageal centers approved this study. Written informed consent was waived because all subjects had completed treatment, the study only used anonymized patient information, and the study was designed as a retrospective observational study with no interventions or invasive procedures. Following the Ethics Committee’s approval of this study, a document was made public to provide information about the research’s goals as well as the option to opt out.

Conflict of interest

All authors have no conflicts of interest and source of funding regarding this research. Yuko Kitagawa; Relevant Financial Activities Outside the Submitted Work: CHUGAI PHARMACEUTICAL CO., LTD. TAIHO PHARMACEUTICAL CO., LTD Yakult Honsha Co. Ltd. ASAHI KASEI PHARMA CORPORATION Otsuka Pharmaceutical Co., Ltd. Takeda Pharmaceutical Co., Ltd. ONO PHARMACEUTICAL CO., LTD. TSUMURA & CO. Kyouwa Hakkou Kirin Co., Ltd. EA Pharma Co., Ltd. MEDICON INC. KAKEN PHARMACEUTICAL CO. LTD. Eisai Co., Ltd. Otsuka Pharmaceutical Factory Inc. TEIJIN PHARMA LIMITED. NIHON PHARMACEUTICAL CO., LTD. Nippon Covidien Inc. SHIONOGI & CO., LTD. Ethicon, Inc. Olympus Corporation Bristol-Myers Squibb K.K. AstraZeneca K.K. MSD K.K. Smith & Nephew KK ASKA Pharmaceutical Co., Ltd. MIYARISAN PHARMACEUTICAL CO. LTD.

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10388_2023_1030_MOESM1_ESM.pptx

Supplementary file1 Supplemental Figure 1. Survival analysis in patients with ypT0 stratified by the pretherapeutic and pathological lymph node metastasis. (PPTX 294 KB)

Supplementary file2 Supplemental Figure 2. Time to recurrence analysis in patients with NAC and NACRT. (PPTX 110 KB)

Supplementary file3 (DOCX 42 KB)

Supplementary file4 (DOCX 23 KB)

Supplementary file5 (DOCX 29 KB)

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Okamura, A., Watanabe, M., Okui, J. et al. Outcomes of patients with esophageal squamous cell carcinoma who achieved a pathological complete response in the primary lesion by neoadjuvant treatment: a Japanese nationwide cohort study. Esophagus 21, 2–10 (2024). https://doi.org/10.1007/s10388-023-01030-y

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