
==== Front
Int J Surg
Int J Surg
JS9
International Journal of Surgery (London, England)
1743-9191
1743-9159
Lippincott Williams & Wilkins Hagerstown, MD

38801467
IJS-D-24-01858
10.1097/JS9.0000000000001657
00079
3
Correspondence
Comment on ‘Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis’
Zhao Jingwen MD qa1122334@126.com
a
Xu Qiang MD bcd*17735907288@163.com

a Tianjin University of Traditional Chinese Medicine
b Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
c Institute of Surgery of Traditional Chinese Medicine
d Institute of Sores and Ulcers, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China
* Corresponding author. Address: Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China. Tel.: +86 022 6063 7062. E-mail: 17735907288@163.com (Q. Xu).
9 2024
27 5 2024
110 9 58955896
6 5 2024
8 5 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

OPEN-ACCESSTRUE
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pmc Dear Editor,

We read with great interest the recent systematic review and meta-analysis that investigated the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma1. This article presents a systematic review and meta-analysis on the application of liquid biopsy, specifically ctDNA analysis, in urothelial carcinoma, highlighting its potential role in prognostic evaluation. It introduces an innovative approach by leveraging ctDNA detection to provide valuable insights for clinical decision-making, including disease burden, treatment response, and prognosis.

The study admirably adheres to established guidelines, ensuring methodological rigor and reliability. However, the wide heterogeneity in ctDNA detection methods and analytical approaches across studies presents a notable challenge. Various techniques, such as digital PCR, NGS, and ddPCR, each have their strengths and limitations2. For example, digital PCR offers high sensitivity and absolute quantification, while NGS allows for comprehensive genomic profiling. However, standardization is lacking, leading to inconsistencies in results. Efforts toward harmonizing protocols, such as the development of reference materials and proficiency testing programs, are crucial to improving reproducibility and comparability across studies.

Moreover, while blood-based sampling is prevalent in current research, urine-based ctDNA analysis holds promise as a non-invasive alternative. Urine directly contacts the urothelial carcinoma site, potentially providing more specific and sensitive detection. Additionally, urine contains higher ctDNA concentrations than blood in certain cases, further emphasizing its utility. Recent studies have demonstrated the feasibility and clinical relevance of urine-based ctDNA analysis in urothelial carcinoma, highlighting its potential as a complementary or alternative approach to blood-based sampling3. However, challenges such as sample contamination and variability in urine composition need to be addressed to optimize urine-based ctDNA analysis. Future research efforts should prioritize exploring the feasibility and potential advantages of urine-based ctDNA analysis in urothelial carcinoma prognosis.

While the study underscores the association between ctDNA dynamics and clinical outcomes, translating these findings into clinical practice requires further elucidation. Optimal timing and frequency of ctDNA monitoring, as well as its integration with existing diagnostic and prognostic modalities, necessitate exploration4. Additionally, investigating the underlying biological mechanisms driving ctDNA changes during disease progression and treatment response is essential for a deeper understanding of tumor biology and therapeutic resistance mechanisms.

The study’s emphasis on the potential of ctDNA in guiding immunotherapy decisions is commendable. However, the interplay between ctDNA profiles and immunotherapy response is complex and multifaceted. While ctDNA analysis has shown promise in predicting immunotherapy outcomes, challenges remain in deciphering the underlying mechanisms and identifying robust predictive biomarkers. Recent studies have implicated tumor mutational burden (TMB) and specific genomic alterations detected in ctDNA as potential predictors of immunotherapy response5. Additionally, immune-related biomarkers, such as tumor-infiltrating lymphocytes and immune checkpoint expression, may further refine patient selection for immunotherapy. However, validation in larger cohorts and prospective trials is needed to establish the clinical utility of ctDNA-based predictors in guiding immunotherapy decisions. Furthermore, efforts to mitigate immune-related adverse events associated with ctDNA alterations are essential to ensure patient safety and optimize treatment outcomes.

Beyond prognostication, ctDNA analysis holds promise for identifying actionable genomic alterations in urothelial carcinoma. Specific gene mutations detected in ctDNA may inform treatment selection and targeted therapy approaches. However, challenges remain in accurately detecting and interpreting these alterations, particularly in the context of tumor heterogeneity and clonal evolution. Further research efforts should focus on validating the prognostic significance of specific mutations in ctDNA and elucidating their functional implications in urothelial carcinoma progression and treatment response.

In conclusion, while the systematic review and meta-analysis provide valuable insights into the prognostic utility of ctDNA in urothelial carcinoma, several key challenges and areas for further investigation emerge. Addressing these challenges through interdisciplinary collaboration and innovative research approaches will be essential for realizing the full potential of ctDNA analysis in revolutionizing urothelial carcinoma management and improving patient outcomes.

Ethical approval

Not applicable.

Consent

Not applicable.

Source of funding

Not applicable.

Author contribution

J.Z.: conceptualization, writing–original draft, and writing–review and editing; Q.X.: conceptualization and writing–review and editing.

Conflicts of interest disclosure

The authors declare no conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Qiang Xu, e-mail: 17735907288@163.com.

Data availability statement

Data availability is not applicable to this article as no new data were created or analyzed in this study.

Provenance and peer review

Not applicable.

Acknowledgements

Not applicable.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Published online 27 May 2024
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References

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