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Prognostic Benefit of Additional Treatment After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma

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Abstract

Background

Although additional treatment is considered for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD), the actual benefits of this method remain to be elucidated.

Aims

We aimed to evaluate the prognostic benefits of additional treatment in such patients.

Methods

Between 2006 and 2017, we enrolled patients with pT1a-MM/pT1b-SM ESCC after ESD at 21 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were compared between the additional treatment and follow-up groups after propensity score matching, to reduce the bias of baseline characteristics. A subgroup analysis was performed according to the pathological findings: category A, pT1a-MM but negative for lymphovascular invasion (LVI) and vertical margin (VM); category B, tumor invasion into the submucosa ≤ 200 μm but negative for LVI and VM; category C, others.

Results

Of 593 patients with pT1a-MM/pT1b-SM ESCC after ESD, 101 matched pairs were extracted after propensity score matching. The OSs were similar between the additional treatment and follow-up groups (80.6% vs. 78.6% in 5 years; P = 0.972). In a subgroup analysis, the OS in the additional treatment group was significantly lower than that in the follow-up group (65.7% vs. 95.2% in 5 years; P = 0.037) in category A, whereas OS did not significantly differ in category C (76.8% vs. 69.5% in 5 years; P = 0.360).

Conclusions

Additional treatment after ESD in patients with pT1a-MM/pT1b-SM ESCC was not associated with an improved prognosis.

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Abbreviations

LNM:

Lymph node metastasis

ESCC:

Esophageal squamous cell carcinoma

pT1a-MM:

Tumor invasion into the muscularis mucosa

pT1b-SM:

Tumor invasion into the submucosa

CRT:

Chemoradiotherapy

OS:

Overall survival

ESD:

Endoscopic submucosal dissection

LVI:

Lymphovascular invasion

VM:

Vertical margin

DSS:

Disease-specific survival

IQR:

Interquartile range

PS:

Propensity score

CCI:

Charlson comorbidity index

PNI:

Prognostic nutrition index

ASD:

Absolute standardized difference

AUROC:

Area under the receiver operating characteristic curve

HR:

Hazard ratio

CI:

Confidence interval

pT1b-SM1:

Tumor invasion into the submucosa ≤ 200 μm

pT1b-SM2:

Tumor invasion into the submucosa > 200 μm

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Acknowledgments

We thank Tamotsu Matsuhashi (Akita University Graduate School of Medicine), Yohei Ogata and Hiroko Abe (Tohoku University Graduate School of Medicine), Yoshihiro Harada, Taku Yamagata, and Yoshiki Koike (Sendai City Medical Center), Mika Takasumi, Minami Hashimoto, and Tsunetaka Kato (Fukushima Medical University Hospital), Yu Sasaki, Makoto Yagi, and Yasuhiko Abe (Yamagata University), Yoshinori Horikawa (Southern-Tohoku General Hospital), Kennichi Satoh and Itaru Satoh (Tohoku Medical and Pharmaceutical University School of Medicine), Ryoichi Ishihata (Ohara General Hospital), Fumitake Ishiyama and Hirohiko Shinkai (Iwate Prefectural Isawa Hospital), Motoki Ohyauchi (Osaki Citizen Hospital), Tetsuya Tatsuta, Hidezumi Kikuchi, and Daisuke Chinda (Hirosaki University Hospital), Wataru Iwai, Tetsuya Noguchi, and Takefumi Miyazaki (Miyagi Cancer Center), Nobuyuki Ara (National Hospital Organization Sendai Medical Center), Shuichi Ohara (Tohoku Rosai Hospital), Jun Fushiya (Iwate Prefectural Central Hospital), Hiroaki Takeda, Nakao Shirahata, and Shoichiro Fujishima (Yamagata Prefectural Central Hospital), and Goro Shibukawa (Fukushima Medical University Aizu Medical Center) for the patient enrollment, data collection, and/or intellectual comment.

Funding

There are no grant supports in this study.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan

    So Takahashi, Kenta Watanabe & Katsunori Iijima

  2. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Waku Hatta, Tomoyuki Koike & Atsushi Masamune

  3. Department of Gastroenterology, Sendai City Medical Center, Sendai, Miyagi, Japan

    Tomohiro Shimada & Tetsuya Ohira

  4. Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan

    Takuto Hikichi & Jun Nakamura

  5. Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Yahaba, Iwate, Japan

    Yosuke Toya & Takayuki Matsumoto

  6. Department of Gastroenterology, Sendai Kousei Hospital, Sendai, Miyagi, Japan

    Ippei Tanaka & Dai Hirasawa

  7. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yusuke Onozato

  8. Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan

    Koichi Hamada

  9. Department of Gastroenterology, Southern-Tohoku General Hospital, Koriyama, Fukushima, Japan

    Koichi Hamada

  10. Division of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, Sendai, Miyagi, Japan

    Daisuke Fukushi

  11. Department of Gastroenterology, Ohara General Hospital, Fukushima, Japan

    Ko Watanabe

  12. Department of Gastroenterology, Iwate Prefectural Isawa Hospital, Ohshu, Iwate, Japan

    Shoichi Kayaba

  13. Department of Gastroenterology, Osaki Citizen Hospital, Osaki, Miyagi, Japan

    Hirotaka Ito

  14. Division of Endoscopy, Hirosaki University Hospital, Hirosaki, Aomori, Japan

    Tatsuya Mikami

  15. Department of Gastroenterology, Miyagi Cancer Center, Natori, Miyagi, Japan

    Tomoyuki Oikawa

  16. Department of Gastroenterology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan

    Yasushi Takahashi

  17. Department of Gastroenterology, Tohoku Rosai Hospital, Sendai, Miyagi, Japan

    Yutaka Kondo

  18. Department of Gastroenterology, Aomori City Hospital, Aomori, Japan

    Tetsuro Yoshimura

  19. Department of Gastroenterology, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan

    Takeharu Shiroki

  20. Department of Gastroenterology, Yamagata Prefectural Central Hospital, Yamagata, Japan

    Ko Nagino

  21. Division of Endoscopy, Aomori Prefectural Central Hospital, Aomori, Japan

    Norihiro Hanabata

  22. Department of Gastroenterology, Fukushima Medical University Aizu Medical Center, Fukushima, Japan

    Akira Funakubo

  23. Department of Health Record Informatics, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan

    Tomohiro Nakamura

  24. Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan

    Naoki Nakaya

  25. National University Corporation Hirosaki University, Hirosaki, Aomori, Japan

    Shinsaku Fukuda

Authors
  1. So Takahashi
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  2. Waku Hatta
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  32. Katsunori Iijima
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Contributions

Conceptualization: WH, KI; Methodology: ST, WH, KI; Acquisition of data: ST, WH, KW, TS, TH, YT, IT, YO, KH, DF, KW, SK, HI, TM, TO, YT, YK, TY, TS, KN, NH, AF, DH, TO, JN; Formal analysis and investigation: ST, WH; Statistical review: TN, NN; Writing—original draft preparation: ST, WH; Writing—review and editing: TK, KI; Supervision: TM, SF, AM, KI.

Corresponding author

Correspondence to Waku Hatta.

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Conflict of interest

Katsunori Iijima received lecture fees from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd. All other authors declare no conflicts of interest.

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Takahashi, S., Hatta, W., Watanabe, K. et al. Prognostic Benefit of Additional Treatment After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma. Dig Dis Sci 68, 2050–2060 (2023). https://doi.org/10.1007/s10620-022-07746-8

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  • DOI: https://doi.org/10.1007/s10620-022-07746-8

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