Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2019; 25(48): 6939-6948
Published online Dec 28, 2019. doi: 10.3748/wjg.v25.i48.6939
Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA
Lucie Benešová, Tereza Hálková, Renata Ptáčková, Anastasiya Semyakina, Kateřina Menclová, Jiří Pudil, Miroslav Ryska, Miroslav Levý, Jaromír Šimša, Filip Pazdírek, Jiří Hoch, Milan Blaha, Marek Minárik
Lucie Benešová, Tereza Hálková, Renata Ptáčková, Anastasiya Semyakina, Marek Minárik, Centre for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague CZ 161 00, Czech Republic
Kateřina Menclová, Jiří Pudil, Miroslav Ryska, Surgery Department, 2nd Faculty of Medicine of Charles University Prague and Military University Hospital, Prague CZ 169 02, Czech Republic
Miroslav Levý, Jaromír Šimša, Surgery Department, 1st Faculty of Medicine, Charles University Prague and Thomayer Hospital, Prague CZ 140 59, Czech Republic
Filip Pazdírek, Jiří Hoch, Surgery Department, 2nd Faculty of Medicine of Charles University Prague and Motol University Hospital, Prague CZ 150 06, Czech Republic
Milan Blaha, Institute of Biostatistics and Analyses of the Masaryk University, Brno CZ 625 00, Czech Republic
Marek Minárik, Elphogene, Prague CZ 161 00, Czech Republic
Author contributions: Benešová L, Minárik M, Ryska M, Hoch J and Levý M designed the study; Hálková T, Semyakina A, Ptáčková R, Menclová K, Pudil J, Pazdírek F, Šimša and Levý M performed the research; Blaha M and Minárik M analyzed the data; Benešová L, Hálková T and Ptáčková R wrote the paper; and Minárik M, Ryska M, Hoch J and Levý M revised the manuscript for final submission.
Supported by the Ministry of Health of the Czech Republic, No. 15-27939A.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Military University Hospital, Thomayer Hospital and Motol University Hospital, Prague.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: Technical and clinical data is available from the corresponding author at Participants have consented to use of their data for further research and other non-commercial purposes.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Lucie Benešová, RNDr., Ph.D., Director, Senior Scientist, Centre for Applied Genomics of Solid Tumors, Genomac Research Institute, Drnovská 1112/60, Prague CZ 161 00, Czech Republic.
Received: October 29, 2019
Peer-review started: October 29, 2019
First decision: November 22, 2019
Revised: December 5, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: December 28, 2019

One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a “liquid (re)biopsy” it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient’s body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.


To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.


A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.


Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers.


ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

Keywords: Circulating tumor DNA, Metastatic colorectal cancer, Postoperative, Radicality of resection, Follow-up, Recurrence

Core tip: Circulating tumor DNA has shown itself to be a highly specific and sensitive tool for confirming the radicality of surgical treatment in patients with metastatic colorectal cancer and for the potential prediction of early disease recurrence after R0/R1 surgeries. Additionally, when compared to imaging methods and tumor markers, circulating tumor DNA more accurately indicates disease recurrence during follow-ups that are minimally invasive and are of low burden to the patient.