Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Jan M van Rees; Lissa Wullaert; Alexander A J Grüter; Yassmina Derraze; Pieter J Tanis; Henk M W Verheul; John W M Martens; Saskia M Wilting; Geraldine Vink; Jeroen L A van Vugt; Nick Beije; Cornelis Verhoef

doi:10.3389/fonc.2023.1083285

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Front Oncol. 2023 Jan 30:13:1083285. doi: 10.3389/fonc.2023.1083285. eCollection 2023.

Affiliations

¹ Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
² Department of Surgery, Amsterdam University Medical Centres (UMC), Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands.
³ Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
⁴ Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁵ Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht, Netherlands.

Abstract

Background: Circulating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.

Methods: A comprehensive search for studies published prior to the 4^th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).

Results: A total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 - 18.8]) and after surgery (HR for RFS: 15.5 [8.2 - 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.

Conclusions: This literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.

Keywords: Ctdna (circulating tumour DNA); cfDNA (circulating free DNA); liquid biopsy; minimal residual disease (MRD); rectal cancer.

Publication types

Systematic Review