Prognostic significance of doubling time in patients undergoing radical surgery for metachronous peritoneal metastases of colorectal cancer
- 10 Downloads
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.
KeywordsDoubling time Peritoneal metastases Colorectal cancer Prognosis
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.
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.
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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.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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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 CrossRefGoogle Scholar
- 26.Japanese Society for Cancer of the Colon and Rectum (2013) Japanese classification of colorectal carcinoma, 8th edn. Kane- hara & Co., Ltd., TokyoGoogle Scholar
- 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 CrossRefGoogle Scholar
- 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
- 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 CrossRefGoogle Scholar
- 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 34:2363–2368Google Scholar
- 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 CrossRefGoogle Scholar