Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2025.023

Minimal residual disease and prognostic significance of circulating tumour cells in early-stage colorectal cancer

Benjamin Tolmaci1, Pavel Stejskal2, Peter Zuffa1, Alona Rehulkova2, Pavla Kourilova2, Emil Berta2, 3, Marian Hajduch2, Jiri Klein1, 4, Josef Srovnal2
1 Department of Surgery, Tomas Bata Hospital Zlin, Czech Republic
2 Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
3 Ringerike Hospital, VVHF, Honefoss, Norway
4 Faculty of Healthcare, Alexander Dubcek University of Trencin, Slovak Republic

Aim: The recurrence rate of colorectal cancer remains high even after radical surgery. Existing criteria for administering adjuvant treatment lack sufficient precision, often leading to undertreatment or overtreatment. This study investigates circulating tumour cells (CTCs) as a potential prognostic biomarker to improve the accuracy of patient selection.

Methods: Forty-six colorectal cancer patients without distant metastases who underwent radical surgery were enrolled in this prospective study conducted at Tomas Bata Hospital in Zlín. The study protocol was approved by the hospital's Ethics Committee. Circulating tumour cells (CTCs) were measured in peripheral blood samples collected preoperatively, on the second postoperative day, and one month after surgery. CTCs were detected and characterized using semiautomated microscopy. Comprehensive clinicopathological data were recorded as part of standardized perioperative care. The prognostic significance of CTCs was evaluated based on the time to recurrence (TTR) parameter.

Results and Conclusion: Growing evidence from circulating tumour cell (CTC) research supports their potential role as a valuable biomarker in cancer management. In this study involving stage I-III colorectal cancer patients, a recurrence rate of 20% was observed among individuals with detectable CTCs, whereas no recurrence occurred in patients with a sustained absence of CTCs. Despite this apparent difference, the time to recurrence (TTR) did not differ significantly between the groups (log-rank test, P=0.175). Although the result was not statistically significant, the observed trend suggests a possible prognostic value of CTCs that merits investigation in a larger cohort. Furthermore, neither individual time-point measurements nor dynamic changes in CTC levels demonstrated a significant correlation with TTR.

Keywords: colorectal cancer, circulating tumour cells, minimal residual disease, prognosis, time to recurrence

Received: May 9, 2025; Revised: July 14, 2025; Accepted: July 18, 2025; Prepublished online: August 13, 2025 

Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. . Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74(3):229-63. doi: 10.3322/caac.21834 Go to original source... Go to PubMed...
    2. . Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ, Watanabe T. Colorectal cancer. Nat Rev Dis Primers 2015;1:15065. doi: 10.1038/nrdp.2015.65 Go to original source... Go to PubMed...
    3. . Cardoso R, Guo F, Heisser T, De Schutter H, Van Damme N, Nilbert MC, Christensen J, Bouvier AM, Bouvier V, Launoy G, Woronoff AS, Cariou M, Robaszkiewicz M, Delafosse P, Poncet F, Walsh PM, Senore C, Rosso S, Lemmens VEPP, Elferink MAG, Tomąič S, ®agar T, Marques ALM, Marcos-Gragera R, Puigdemont M, Galceran J, Carulla M, Sánchez-Gil A, Chirlaque MD, Hoffmeister M, Brenner H. Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries. Lancet Reg Health Eur 2022;21:100458. doi: 10.1016/j.lanepe.2022.100458 Go to original source... Go to PubMed...
    4. . Storli PE, Dille-Amdam RG, Skjærseth GH, Gran MV, Myklebust TÅ, Grønbech JE, Bringeland EA. Cumulative incidence of first recurrence after curative treatment of stage I-III colorectal cancer. Competing risk analyses of temporal and anatomic patterns. Acta Oncol 2023;62(12):1822-30. doi: 10.1080/0284186X.2023.2269644 Go to original source... Go to PubMed...
    5. . Buyse M, Zeleniuch-Jacquotte A, Chalmers TC. Adjuvant therapy of colorectal cancer. Why we still don't know. JAMA 1988;259(24):3571-8. Go to original source...
    6. . Argilés G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T, Laurent-Puig P, Quirke P, Yoshino T, Taieb J, Martinelli E, Arnold D; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31(10):1291-305. doi: 10.1016/j.annonc.2020.06.022 Go to original source... Go to PubMed...
    7. . Morris EJ, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut 2007;56(10):1419-25. doi: 10.1136/gut.2006.116830 Go to original source... Go to PubMed...
    8. . Kannarkatt J, Joseph J, Kurniali PC, Al-Janadi A, Hrinczenko B. Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma. J Oncol Pract 2017;13(4):233-41. doi: 10.1200/JOP.2016.017210 Go to original source... Go to PubMed...
    9. . Chakrabarti S, Peterson CY, Sriram D, Mahipal A. Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions. World J Gastrointest Oncol 2020;12(8):808-32. doi: 10.4251/wjgo.v12.i8.808 Go to original source... Go to PubMed...
    10. . Smit DJ, Schneegans S, Pantel K. Clinical applications of circulating tumor cells in patients with solid tumors. Clin Exp Metastasis 2024;41(4):403-11. doi: 10.1007/s10585-024-10267-5 Go to original source... Go to PubMed...
    11. . Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 1869;14:146-7.
    12. . Hu M, Wang Z, Wu Z, Ding P, Pei R, Wang Q, Xing C. Circulating tumor cells in colorectal cancer in the era of precision medicine. J Mol Med (Berl) 2022;100(2):197-213. doi: 10.1007/s00109-021-02162-3 Go to original source... Go to PubMed...
    13. . Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004;10(24):8152-62. doi: 10.1158/1078-0432.CCR-04-1110 Go to original source... Go to PubMed...
    14. . Heidrich I, Abdalla TSA, Reeh M, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer. Cancers (Basel) 2021;13(18):4500. doi: 10.3390/cancers13184500 Go to original source... Go to PubMed...
    15. . Vidlarova M, Rehulkova A, Stejskal P, Prokopova A, Slavik H, Hajduch M, Srovnal J. Recent Advances in Methods for Circulating Tumor Cell Detection. Int J Mol Sci 2023;24(4):3902. doi: 10.3390/ijms24043902 Go to original source... Go to PubMed...
    16. . Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004;10(20):6897-904. doi: 10.1158/1078-0432.CCR-04-0378 Go to original source... Go to PubMed...
    17. . Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, Meropol NJ. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 2008;26(19):3213-21. doi: 10.1200/JCO.2007.15.8923 Erratum in: J Clin Oncol 2009;27(11):1923. Go to original source... Go to PubMed...
    18. . Alix-Panabières C, Mader S, Pantel K. Epithelial-mesenchymal plasticity in circulating tumor cells. J Mol Med (Berl) 2017;95(2):133-42. doi: 10.1007/s00109-016-1500-6 Go to original source... Go to PubMed...
    19. . Hillig T, Horn P, Nygaard AB, Haugaard AS, Nejlund S, Brandslund I, Sölétormos G. In vitro detection of circulating tumor cells compared by the CytoTrack and CellSearch methods. Tumour Biol 2015;36(6):4597-601. doi: 10.1007/s13277-015-3105-z Go to original source... Go to PubMed...
    20. . Salu P, Reindl KM. Advancements in Circulating Tumor Cell Research: Bridging Biology and Clinical Applications. Cancers (Basel) 2024;16(6):1213. doi: 10.3390/cancers16061213 Go to original source... Go to PubMed...
    21. . Yang C, Zou K, Zheng L, Xiong B. Prognostic and clinicopathological significance of circulating tumor cells detected by RT-PCR in non-metastatic colorectal cancer: a meta-analysis and systematic review. BMC Cancer 2017;17(1):725. doi: 10.1186/s12885-017-3704-8 Go to original source... Go to PubMed...
    22. . Kaifi JT, Kunkel M, Zhu J, Dicker DT, Gusani N, Yang Z, Sarwani NE, Li G, Kimchi ET, Staveley-O'Carroll KF, El-Deiry WS. Circulating tumor cells are associated with diffuse spread in stage IV colorectal cancer patients. Cancer Biol Ther 2013;14(12):1174-81. doi: 10.4161/cbt.26884 Go to original source... Go to PubMed...
    23. . Kaifi JT, Kunkel M, Dicker DT, Joude J, Allen JE, Das A, Zhu J, Yang Z, Sarwani NE, Li G, Staveley-O'Carroll KF, El-Deiry WS. Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver. Cancer Biol Ther 2015;16(5):690-8. doi: 10.1080/15384047.2015.1026508 Go to original source... Go to PubMed...
    24. . Baek DH, Kim GH, Song GA, Han IS, Park EY, Kim HS, Jo HJ, Ko SH, Park DY, Cho YK. Clinical Potential of Circulating Tumor Cells in Colorectal Cancer: A Prospective Study. Clin Transl Gastroenterol 2019;10(7):e00055. doi: 10.14309/ctg.0000000000000055 Go to original source... Go to PubMed...
    25. . Eliasova P, Pinkas M, Kolostova K, Gurlich R, Bobek V. Circulating tumor cells in different stages of colorectal cancer. Folia Histochem Cytobiol 2017;55(1):1-5. doi: 10.5603/FHC.a2017.0005 Go to original source... Go to PubMed...
    26. . Tan Y, Wu H. The significant prognostic value of circulating tumor cells in colorectal cancer: A systematic review and meta-analysis. Curr Probl Cancer 2018;42(1):95-106. doi: 10.1016/j.currproblcancer.2017.11.002 Go to original source... Go to PubMed...
    27. . Lu YJ, Wang P, Peng J, Wang X, Zhu YW, Shen N. Meta-analysis Reveals the Prognostic Value of Circulating Tumour Cells Detected in the Peripheral Blood in Patients with Non-Metastatic Colorectal Cancer. Sci Rep 2017;7(1):905. doi: 10.1038/s41598-017-01066-y Go to original source... Go to PubMed...
    28. . Sotelo MJ, Sastre J, Maestro ML, Veganzones S, Viéitez JM, Alonso V, Grávalos C, Escudero P, Vera R, Aranda E, García-Alfonso P, Gallego-Plazas J, Lopez C, Pericay C, Arrivi A, Vicente P, Ballesteros P, Elez E, López-Ladrón A, Díaz-Rubio E. Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer. Ann Oncol 2015;26(3):535-41. doi: 10.1093/annonc/mdu568 Go to original source... Go to PubMed...
    29. . Le UT, Bronsert P, Picardo F, Riethdorf S, Haager B, Rylski B, Czerny M, Beyersdorf F, Wiesemann S, Pantel K, Passlick B, Kaifi JT, Schmid S. Intraoperative detection of circulating tumor cells in pulmonary venous blood during metastasectomy for colorectal lung metastases. Sci Rep 2018;8(1):8751. doi: 10.1038/s41598-018-26410-8 Erratum in: Sci Rep 2020;10(1):7633. doi: 10.1038/s41598-020-64151-9 Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return