Prognostic significance of doubling time in patients undergoing radical surgery for metachronous peritoneal metastases of colorectal cancer

  • Hiroaki MiyakeEmail author
  • Koji Murono
  • Hiroshi Nagata
  • Hiroaki Nozawa
  • Kazushige Kawai
  • Keisuke Hata
  • Toshiaki Tanaka
  • Takeshi Nishikawa
  • Yasutaka Shuno
  • Kazuhito Sasaki
  • Soichiro Ishihara
Original Article



The doubling times of tumor volume and tumor markers are associated with the prognosis of liver or lung metastases from colorectal cancer (CRC). However, no studies have assessed peritoneal metastases. Therefore, we aimed to elucidate the association between doubling time and the prognosis of patients who underwent radical surgery for metachronous peritoneal metastases of CRC.


We calculated the tumor doubling times (TDT) of peritoneal metastases and serum carcinoembryonic antigen-doubling times (CEA-DT) in 33 consecutive patients who underwent radical surgery for metachronous peritoneal metastases between January 2006 and April 2017. The impact of short TDT and CEA-DT on overall survival (OS) and relapse-free survival (RFS) was retrospectively reviewed.


In long TDT (> 137 days) group, the 5-year OS rate was 74.1% and median OS time was 6.6 years. In long CEA-DT (> 102 days) group, the 5-year OS rate was 50.0% and median OS time was 5.6 years. Conversely, in short TDT (≤ 137 days) and CEA-DT (≤ 102 days) group, the 5-year OS rates and median OS times were both 0.0% and 3.2 years, respectively. In the multivariate analysis, short TDT was an independent risk factor for poor RFS (P = 0.006) and OS (P = 0.010). Similarly, short CEA-DT was also a poor risk factor for RFS (P < 0.001) and OS (P = 0.012).


Short TDT and CEA-DT are independent risk factors for poor OS and RFS after surgery for metachronous peritoneal metastases of CRC. TDT and CEA-DT should be considered when selecting candidates for surgical resection.


Doubling time Peritoneal metastases Colorectal cancer Prognosis 


Authors’ contribution

HM established the study concept and design, acquired the data, and drafted the manuscript. All co-authors contributed to this study, especially as described below in all criteria. KM established the study concept and design and revised the manuscript. HN, HN, KH, and SI revised the manuscript. KK maintained the databases and revised the manuscript. TT, TN, YS, and KS analyzed and interpreted the data.

Funding information

This research was supported by Grants-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (grant numbers: 16K07143, 16K07161, 17K10620, 17K10621, 17K10623, and 18K07194) and by the Project for Cancer Research and Therapeutic Evolution from the Japan Agency for Medical Research and Development (grant number: JP18cm0106502h0003).

Compliance with ethical standards

The study protocol was approved by the Ethics Committee of The University of Tokyo (approval number: 3252-(7)).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hiroaki Miyake
    • 1
    Email author
  • Koji Murono
    • 1
  • Hiroshi Nagata
    • 1
  • Hiroaki Nozawa
    • 1
  • Kazushige Kawai
    • 1
  • Keisuke Hata
    • 1
  • Toshiaki Tanaka
    • 1
  • Takeshi Nishikawa
    • 1
  • Yasutaka Shuno
    • 1
  • Kazuhito Sasaki
    • 1
  • Soichiro Ishihara
    • 1
  1. 1.Department of Surgical OncologyThe University of TokyoTokyoJapan

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