Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA

World J Gastroenterol. 2019 Dec 28;25(48):6939-6948. doi: 10.3748/wjg.v25.i48.6939.

Abstract

Background: 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.

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

Methods: 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.

Results: 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.

Conclusion: 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; Follow-up; Metastatic colorectal cancer; Postoperative; Radicality of resection; Recurrence.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / isolation & purification
  • Circulating Tumor DNA / blood*
  • Circulating Tumor DNA / isolation & purification
  • Colectomy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Czech Republic
  • Disease Progression
  • Early Detection of Cancer / methods*
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Liquid Biopsy / methods
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / secondary
  • Male
  • Margins of Excision
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control
  • Postoperative Period
  • Prospective Studies
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA