Advertisement

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
  • 156 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

Doubling time Peritoneal metastases Colorectal cancer Prognosis 

Notes

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.

References

  1. 1.
    Cass AW, Million RR, Pfaff WW (1976) Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer 37:2861–2865CrossRefPubMedGoogle Scholar
  2. 2.
    van Gestel YR, Thomassen I, Lemmens VE, Pruijt JF, van Herk-Sukel MP, Rutten HJ, Creemers GJ, de Hingh IH (2014) Metachronous peritoneal carcinomatosis after curative treatment of colorectal cancer. Eur J Surg Oncol 40:963–969.  https://doi.org/10.1016/j.ejso.2013.10.001 CrossRefPubMedGoogle Scholar
  3. 3.
    Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A (2012) Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg 99:699–705.  https://doi.org/10.1002/bjs.8679 CrossRefPubMedGoogle Scholar
  4. 4.
    Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ (2012) Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol 30:263–267.  https://doi.org/10.1200/JCO.2011.37.1039 CrossRefPubMedGoogle Scholar
  5. 5.
    Franko J, Shi Q, Meyers JP, Maughan TS, Seymour MT, Saltz L et al (2016) Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the analysis and research in cancers of the digestive system (ARCAD) database. Lancet Oncol 17:1709–1719.  https://doi.org/10.1016/S1470-2045(16)30500-9 CrossRefPubMedGoogle Scholar
  6. 6.
    Sugarbaker PH, Ryan DP (2012) Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol 13:e362–e369.  https://doi.org/10.1016/S1470-2045(12)70210-3 CrossRefPubMedGoogle Scholar
  7. 7.
    Goéré D, Malka D, Tzanis D, Gava V, Boige V, Eveno C, Maggiori L, Dumont F, Ducreux M, Elias D (2013) Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg 257:1065–1071.  https://doi.org/10.1097/SLA.0b013e31827e9289 CrossRefPubMedGoogle Scholar
  8. 8.
    Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21:3737–3743.  https://doi.org/10.1200/JCO.2003.04.187 CrossRefPubMedGoogle Scholar
  9. 9.
    Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H (2008) 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 15:2426–2432.  https://doi.org/10.1245/s10434-008-9966-2 CrossRefPubMedGoogle Scholar
  10. 10.
    Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M et al (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 22:3284–3292CrossRefGoogle Scholar
  11. 11.
    Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, Lorimier G, Dube P, Glehen O (2010) Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 28:63–68.  https://doi.org/10.1200/JCO.2009.23.9285 CrossRefPubMedGoogle Scholar
  12. 12.
    Yan TD, Black D, Savady R, Sugarbaker PH (2006) Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol 24:4011–4019CrossRefPubMedGoogle Scholar
  13. 13.
    Cashin PH, Graf W, Nygren P, Mahteme H (2012) Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study. Ann Oncol 23:647–652.  https://doi.org/10.1093/annonc/mdr301 CrossRefPubMedGoogle Scholar
  14. 14.
    Goéré D, Souadka A, Faron M, Cloutier AS, Viana B, Honoré C, Dumont F, Elias D (2015) Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study. Ann Surg Oncol 22:2958–2964.  https://doi.org/10.1245/s10434-015-4387-5 CrossRefPubMedGoogle Scholar
  15. 15.
    Collins VP, Loeffler RK, Tivey H (1956) Observations on growth rates of human tumors. Am J Roentgenol Radium Therapy, Nucl Med 76:988–1000Google Scholar
  16. 16.
    Collins VP (1962) Time of occurrence of pulmonary metastasis from carcinoma of colon and rectum. Cancer 15:387–395CrossRefPubMedGoogle Scholar
  17. 17.
    Tanaka K, Shimada H, Ueda M, Matsuo K, Endo I, Togo S (2007) Long-term characteristics of 5-year survivors after liver resection for colorectal metastases. Ann Surg Oncol 14:1336–1346CrossRefPubMedGoogle Scholar
  18. 18.
    Tanaka K, Shimada H, Fujii Y, Endo I, Sekido H, Togo S, Ike H (2004) Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver. Langenbeck's Arch Surg 389:371–379.  https://doi.org/10.1007/s00423-004-0490-y CrossRefGoogle Scholar
  19. 19.
    Koga H, Moriya Y, Akasu T, Fujita S (1999) The relationship between prognosis and CEA-dt after hepatic resection in patients with colorectal carcinomas. Eur J Surg Oncol 25:292–296.  https://doi.org/10.1053/ejso.1998.0644 CrossRefPubMedGoogle Scholar
  20. 20.
    Nomura K, Miyagawa S, Harada H, Kitamura H, Seki H, Shimada R, Kobayashi A, Noike T, Kawasaki S (1998) Relationship between doubling time of liver metastases from colorectal carcinoma and residual primary cancer. Dig Surg 15:21–24.  https://doi.org/10.1159/000018581 CrossRefPubMedGoogle Scholar
  21. 21.
    Kito A, Tanaka K, Fujimaki H, Nakazawa M, Togo S, Minami M, Shimada H (2007) Tumor doubling time and local immune response to hepatic metastases from colorectal cancer. J Surg Oncol 96:525–533.  https://doi.org/10.1002/jso.20806 CrossRefPubMedGoogle Scholar
  22. 22.
    Kawaguchi K, Uehara K, Nakayama G, Fukui T, Fukumoto K, Nakamura S, Yokoi K (2016) Growth rate of chemotherapy-naïve lung metastasis from colorectal cancer could be a predictor of early relapse after lung resection. Int J Clin Oncol 21:329–334.  https://doi.org/10.1007/s10147-015-0889-1 CrossRefPubMedGoogle Scholar
  23. 23.
    Tomimaru Y, Noura S, Ohue M, Okami j OK, Higashiyama M et al (2008) Metastatic tumor doubling time is an independent predictor of intrapulmonary recurrence after pulmonary resection of solitary pulmonary metastasis from colorectal cancer. Dig Surg 25:220–225.  https://doi.org/10.1159/000140693 CrossRefPubMedGoogle Scholar
  24. 24.
    Tanaka K, Noura S, Ohue M, Seki Y, Yamada T, Miyashiro I, Ohigashi H, Yano M, Ishikawa O, Murata K, Kameyama M, Imaoka S (2008) Doubling time of carcinoembryonic antigen is a significant prognostic factor after the surgical resection of locally recurrent rectal cancer. Dig Surg 25:319–324.  https://doi.org/10.1159/000158597 CrossRefPubMedGoogle Scholar
  25. 25.
    Maetani S, Onodera H, Nishikawa T, Morimoto H, Ida K, Kitamura O, Imamura M (1998) Significance of local recurrence of rectal cancer as a local or disseminated disease. Br J Surg 85:521–525CrossRefPubMedGoogle Scholar
  26. 26.
    Japanese Society for Cancer of the Colon and Rectum (2013) Japanese classification of colorectal carcinoma, 8th edn. Kane- hara & Co., Ltd., TokyoGoogle Scholar
  27. 27.
    Shida D, Yoshida T, Tanabe T, Tsukamoto S, Ochiai H, Kanemitsu Y (2018) Prognostic impact of R0 resection and targeted therapy for colorectal cancer with synchronous peritoneal metastasis. Ann Surg Oncol 25:1646–1653.  https://doi.org/10.1245/s10434-018-6436-3 CrossRefPubMedGoogle Scholar
  28. 28.
    Schwartz M (1961) A biomathematical approach to clinical tumor growth. Cancer 14:1272–1294CrossRefPubMedGoogle Scholar
  29. 29.
    Miyauchi A, Onishi T, Morimoto S, Takai S, Matsuzuka F, Kuma K, Maeda M, Kumahara Y (1984) Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg 199:461–466CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Spratt JS Jr, Spratt TL (1964) Rates of growth of pulmonary metastases and host survival. Ann Surg 159:161–171CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tanaka K, Shimada H, Miura M, Fujii Y, Yamaguchi S, Endo I, Sekido H, Togo S, Ike H (2004) Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 28:263–270.  https://doi.org/10.1007/s00268-003-7088-3 CrossRefPubMedGoogle Scholar
  32. 32.
    Coccolini F, Gheza F, Lotti M, Virzì S, Iusco D, Ghermandi C, Melotti R, Baiocchi G, Giulini SM, Ansaloni L, Catena F (2013) Peritoneal carcinomatosis. World J Gastroenterol 19:6979–6994.  https://doi.org/10.3748/wjg.v19.i41.6979 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Sodek KL, Murphy KJ, Brown TJ, Ringuette MJ (2012) Cell-cell and cell-matrix dynamics in intraperitoneal cancer metastasis. Cancer Metastasis Rev 31:397–414.  https://doi.org/10.1007/s10555-012-9351-2 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    de Bree E, Koops W, Kröger R, van Ruth S, Witkamp AJ, Zoetmulder FA (2004) Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement. J Surg Oncol 86:64–73.  https://doi.org/10.1002/jso.20049 CrossRefGoogle Scholar
  35. 35.
    Jacquet P, Jelinek JS, Steves MA, Sugarbaker PH (1993) Evaluation of computed tomography in patients with peritoneal carcinomatosis. Cancer 72:1631–1636CrossRefGoogle Scholar
  36. 36.
    Esquivel J, Sticca R, Sugarbaker P, Levine E, Yan TD, Alexander R et al (2007) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol 14:128–133.  https://doi.org/10.1245/s10434-006-9185-7 CrossRefPubMedGoogle Scholar
  37. 37.
    Pasqual EM, Bertozzi S, Bacchetti S, Londero AP, Basso SM, Santeufemia DA, Lo Re G, Lumachi F (2014) Preoperative assessment of peritoneal carcinomatosis in patients undergoing hyperthermic intraperitoneal chemotherapy following cytoreductive surgery. Anticancer Res 34:2363–2368PubMedGoogle Scholar
  38. 38.
    Marin D, Catalano C, Baski M, Di Martino M, Geiger D, Di Giorgio A, Sibio S, Passariello R (2010) 64-section multi-detector row CT in the preoperative diagnosis of peritoneal carcinomatosis: correlation with histopathological findings. Abdom Imaging 35:694–700.  https://doi.org/10.1007/s00261-008-9464-9 CrossRefPubMedGoogle Scholar
  39. 39.
    Takakura Y, Miyata Y, Okajima M, Okada M, Ohdan H (2010) Short disease-free interval is a significant risk factor for intrapulmonary recurrence after resection of pulmonary metastases in colorectal cancer. Color Dis 12:e68–e75.  https://doi.org/10.1111/j.1463-1318.2009.02070.x CrossRefGoogle Scholar

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

Personalised recommendations