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Old age and intense chemotherapy exacerbate negative prognostic impact of postoperative complication on survival in patients with esophageal cancer who received neoadjuvant therapy: a nationwide study from 85 Japanese esophageal centers

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Abstract

Background

The prognostic impact of docetaxel, cisplatin, and 5-FU (DCF) reported in JCOG1109 was successfully validated using real-world data in patients < 75 years old. However, DCF was not reported to be beneficial in elderly patients with a relatively higher postoperative complication incidence. This study aimed to clarify the impact of postoperative complications on the prognosis of ESCC and the difference in the magnitude of the impact by age and regimen.

Methods

Patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed from 2010 to 2015. The prognostic impact of postoperative anastomotic leakage (AL) and pneumonia on survival was evaluated. The prognostic value of the postoperative complications was assessed by stratifying patients according to age and neoadjuvant chemotherapy regimen.

Results

Patients with AL, pneumonia, and infectious complications (ICs: a combination of pneumonia and AL) showed significantly worse overall survival (OS). IC served as a negative prognostic factor of OS and recurrence-free survival, and its negative prognostic impact was more evident in patients aged > 75 years. When the patients were further stratified by chemotherapeutic regimens, using the CF/IC(−) group as a reference, the DCF/IC (+) group showed significantly shorter OS in patients aged > 75 years with a hazard ratio (HR) of 2.551. The HR of the CF/IC (+) group was 1.503.

Conclusions

The negative impact of postoperative complications on survival was confirmed in this nationwide study. Furthermore, its magnitude was higher in elderly patients who received triplet chemotherapy.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We sincerely appreciate all the partici pating investigators for their valuable assistance with data collection: Sohei Matsumoto (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 University 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). We also wish to extend our gratitude to Kumiko Motooka and Sanae Oikawa, staff of the study team, for their aid in collecting patient data.

Funding

Eisai Co., Ltd., Otsuka Pharmaceutical Factory Inc., TEIJIN PHARMA LIMITED., NIHON PHARMACEUTICAL CO., LTD., Nippon Covidien Inc. Yuko Kitagawa received lecture fees/honoraria from CHUGAI PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD, ASAHI KASEI PHARMA CORPORATION, Otsuka Pharmaceutical Factory Inc., SHIONOGI & CO., LTD., Nippon Covidien Inc., Ethicon, Inc., ONO PHARMACEUTICAL CO., LTD., Olympus Corporation, Bristol-Myers Squibb K.K., AstraZeneca K.K., MSD K.K., Smith & Nephew KK, KAKEN PHARMACEUTICAL CO., LTD., ASKA Pharmaceutical Co., Ltd., MIYARISAN PHARMACEUTICAL CO. LTD.

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Author notes

  1. Jun Okui has equally contributed to this article.

Authors and Affiliations

  1. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan

    Satoru Matsuda, Yuko Kitagawa, Jun Okui & Hirofumi Kawakubo

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

    Jun Okui

  3. Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Akihiko Okamura & Masayuki Watanabe

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

    Ryo Takemura

  5. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Manabu Muto

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

    Yoshihiro Kakeji

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

    Hiroya Takeuchi

  8. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Yuichiro Doki

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  1. Satoru Matsuda
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Corresponding author

Correspondence to Yuko Kitagawa.

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Ethical Statement

This study was approved by the Keio University School of Medicine Ethics Committee and by all the participating esophageal centers.

Conflicts of interest

Yuko Kitagawa received research grants from Takeda Pharmaceutical Co., Ltd., CHUGAI PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD, Yakult Honsha Co. Ltd., ASAHI KASEI PHARMA CORPORATION, Otsuka Pharmaceutical Co., Ltd., ONO PHARMACEUTICAL CO., LTD., TSUMURA & CO., Kyouwa Hakkou Kirin Co., Ltd., DAINIPPON SUMITOMO PHARMA Co., Ltd., EA Pharma Co., Ltd., MEDICON INC., KAKEN PHARMACEUTICAL CO. LTD.

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Supplementary file1 Supplementary Figure 1. Consort diagram. (TIF 90 KB)

10388_2022_980_MOESM2_ESM.tif

Supplementary file2 Supplementary Figure 2 Cumulative incidence function curve of death. (a) Anastomotic leakage (AL): The subdistribution hazard ratio (sdHR) of cancer-specific death of AL (-) vs. AL (+) was 1.209 (95% CI: 1.028–1.423, p = 0.022) and that of noncancer-specific death was 1.445 (95% CI: 1.089–1.918, p = 0.011). (b) Pneumonia: The sdHR of cancer-specific death of Pneumonia (-) vs. Pneumonia (+) was 1.071 (95% CI: 0.933–1.229, p = 0.333) and that of noncancer-specific death was 1.668 (95% CI: 1.329–2.093, p < 0.001). (c) Anastomotic leakage (AL): The sdHR of cancer-specific death of AL (-) vs. AL (+) was 1.144 (95% CI: 1.016–1.289, p = 0.026) and that of noncancer-specific death was 1.570 (95% CI: 1.275–1.934, p < 0.001). AL, anastomotic leakage; IC, infectious complications. (TIF 173 KB)

Supplementary file3 (DOCX 50 KB)

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Matsuda, S., Kitagawa, Y., Okui, J. et al. Old age and intense chemotherapy exacerbate negative prognostic impact of postoperative complication on survival in patients with esophageal cancer who received neoadjuvant therapy: a nationwide study from 85 Japanese esophageal centers. Esophagus 20, 445–454 (2023). https://doi.org/10.1007/s10388-022-00980-z

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