Cell-Free DNA As a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 14

PMID 36233035

Authors

Raquel Carrasco

Mercedes Ingelmo-Torres

Ascension Gomez

Ramon Trullas

Fiorella L Roldan

Tarek Ajami

Davinia Moreno

Leonardo Rodriguez-Carunchio

Antonio Alcaraz

Laura Izquierdo

Lourdes Mengual

Affiliations

Soon will be listed here.

Abstract

Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; = 0.033) and cancer-specific survival (HR 4.199; = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

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References

Christensen E, Birkenkamp-Demtroder K, Sethi H, Shchegrova S, Salari R, Nordentoft I . Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. J Clin Oncol. 2019; 37(18):1547-1557. DOI: 10.1200/JCO.18.02052. View

Kienel A, Porres D, Heidenreich A, Pfister D . cfDNA as a Prognostic Marker of Response to Taxane Based Chemotherapy in Patients with Prostate Cancer. J Urol. 2015; 194(4):966-71. DOI: 10.1016/j.juro.2015.04.055. View

Oversoe S, Clement M, Pedersen M, Weber B, Aagaard N, Villadsen G . TERT promoter mutated circulating tumor DNA as a biomarker for prognosis in hepatocellular carcinoma. Scand J Gastroenterol. 2020; 55(12):1433-1440. DOI: 10.1080/00365521.2020.1837928. View

Shohdy K, Villamar D, Cao Y, Trieu J, Price K, Nagy R . Serial ctDNA analysis predicts clinical progression in patients with advanced urothelial carcinoma. Br J Cancer. 2022; 126(3):430-439. PMC: 8810988. DOI: 10.1038/s41416-021-01648-8. View

Magbanua M, Swigart L, Wu H, Hirst G, Yau C, Wolf D . Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2020; 32(2):229-239. PMC: 9348585. DOI: 10.1016/j.annonc.2020.11.007. View

Yang Y, Zhang T, Wang J, Wang J, Xu Y, Zhao X . The clinical utility of dynamic ctDNA monitoring in inoperable localized NSCLC patients. Mol Cancer. 2022; 21(1):117. PMC: 9118575. DOI: 10.1186/s12943-022-01590-0. View

Fernandez-Garcia D, Hills A, Page K, Hastings R, Toghill B, Goddard K . Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer. Breast Cancer Res. 2019; 21(1):149. PMC: 6924016. DOI: 10.1186/s13058-019-1235-8. View

De Rubis G, Rajeev Krishnan S, Bebawy M . Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis. Trends Pharmacol Sci. 2019; 40(3):172-186. DOI: 10.1016/j.tips.2019.01.006. View

Pritchard J, Hamilton G, Hurst C, Fraser S, Orange C, Knowles M . Monitoring of urothelial cancer disease status after treatment by digital droplet PCR liquid biopsy assays. Urol Oncol. 2020; 38(9):737.e1-737.e10. DOI: 10.1016/j.urolonc.2020.05.012. View

10.

Hayashi Y, Fujita K, Nojima S, Tomiyama E, Matsushita M, Koh Y . TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical recurrence for patients with non-muscle invasive bladder cancer. Mol Oncol. 2020; 14(10):2375-2383. PMC: 7530786. DOI: 10.1002/1878-0261.12746. View

11.

Birkenkamp-Demtroder K, Christensen E, Nordentoft I, Knudsen M, Taber A, Hoyer S . Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis. Eur Urol. 2017; 73(4):535-540. DOI: 10.1016/j.eururo.2017.09.011. View

12.

Min J, Shay J . TERT Promoter Mutations Enhance Telomerase Activation by Long-Range Chromatin Interactions. Cancer Discov. 2016; 6(11):1212-1214. PMC: 5111399. DOI: 10.1158/2159-8290.CD-16-1050. View

13.

Heitzer E, van den Broek D, Denis M, Hofman P, Hubank M, Mouliere F . Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer. ESMO Open. 2022; 7(2):100399. PMC: 8867049. DOI: 10.1016/j.esmoop.2022.100399. View

14.

Hayashi Y, Fujita K, Matsuzaki K, Eich M, Tomiyama E, Matsushita M . Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer. Front Oncol. 2020; 10:755. PMC: 7250242. DOI: 10.3389/fonc.2020.00755. View

15.

Tan M, Attard G, Huddart R . Circulating Tumour DNA in Muscle-Invasive Bladder Cancer. Int J Mol Sci. 2018; 19(9). PMC: 6165229. DOI: 10.3390/ijms19092568. View

16.

Stewart C, Tsui D . Circulating cell-free DNA for non-invasive cancer management. Cancer Genet. 2018; 228-229:169-179. PMC: 6598437. DOI: 10.1016/j.cancergen.2018.02.005. View

17.

Paik M, Scolieri M, Brown S, Spirnak J, Resnick M . Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy. J Urol. 2000; 163(6):1693-6. View

18.

Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I . Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016; 8(346):346ra92. PMC: 5346159. DOI: 10.1126/scitranslmed.aaf6219. View

19.

Vandekerkhove G, Lavoie J, Annala M, Murtha A, Sundahl N, Walz S . Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer. Nat Commun. 2021; 12(1):184. PMC: 7794518. DOI: 10.1038/s41467-020-20493-6. View

20.

Christensen E, Nordentoft I, Vang S, Birkenkamp-Demtroder K, Jensen J, Agerbaek M . Optimized targeted sequencing of cell-free plasma DNA from bladder cancer patients. Sci Rep. 2018; 8(1):1917. PMC: 5789978. DOI: 10.1038/s41598-018-20282-8. View