Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study - study protocol

Sep 24, 2026

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Locally recurrent rectal cancer (LRRC) is treated with surgery for resectable disease, yet outcomes remain suboptimal due to invasive procedures and a high rate of local recurrence. Reliable prognostic and predictive biomarkers are needed to guide treatment decisions. Circulating tumour DNA (ctDNA) in plasma after surgery may indicate minimal residual disease (MRD). This protocol describes a multi-institutional prospective observational study assessing ctDNA for MRD detection in parallel with the randomized phase III JCOG1801 trial comparing preoperative chemoradiotherapy with up-front surgery.

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Abstract

Introduction

Methods and analysis

Ethics and dissemination

Strengths and limitations of this study

Introduction

Open access Protocol Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study) Tadayoshi Hashimoto ,1,2 Yuichiro Tsukada,3 Masaaki Ito ,3 Keisuke Kanato,1 Junki Mizusawa,1 Haruhiko Fukuda,1 Shunsuke Tsukamoto,4 Atsuo Takashima,5 Yukihide Kanemitsu4 To cite: Hashimoto T, Tsukada Y, Ito M, et al. Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study) . BMJ Open 2023;13:e073217 . doi:10 . 1136/ bmjopen-2023-073217 ► Prepublication history for this paper is available online. To view these files, please visit the journal online ([http://dx.doi](http://dx.doi). org/10 . 1136/bmjopen-2023- 073217) . Received 27 February 2023 Accepted 28 July 2023 © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. For numbered affiliations see end of article. Correspondence to Yuichiro Tsukada; [yutsukad@east.ncc.go.jp](yutsukad@east.ncc.go.jp) ABSTRACT Introduction In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999) . Methods and analysis JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801 . Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy) . Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points. Ethics and dissemination The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ This is the first multi-institutional prospective study to assess the clinical utility of circulating tumour DNA (ctDNA) as a biomarker for patients with resectable locally recurrent rectal cancer (LRRC), concurrent with the randomised phase III trial (JCOG1801) . ⇒ Blood samples will be obtained according to a preestablished protocol schedule in JCOG1801, thus ensuring reliable results for clinical application. ⇒ The analysis of plasma samples will be performed using Guardant Reveal, which can detect ctDNA with a high level of sensitivity, obviating the need for specific molecula

FAQs

Why is ctDNA being studied in locally recurrent rectal cancer (LRRC)?

Because ctDNA in plasma after surgery may reflect minimal residual disease, and the study aims to evaluate ctDNA as a prognostic and predictive biomarker in LRRC.

How will blood samples be collected in the study?

Patients in the up-front surgery arm provide samples at three time points (before surgery, after surgery, after postoperative chemotherapy), while those receiving pre-CRT provide samples at five time points across pre-CRT, surgery, and postoperative chemotherapy.

What method will be used to analyze ctDNA?

Cell-free DNA extracted from plasma will be analyzed using Guardant Reveal, which assesses genomic alterations and methylation patterns to determine ctDNA presence.

Sep 24, 2026

Uploaded by Fahsai