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ctDNA for Risk of Recurrence Assessment in Patients Treated with Neoadjuvant Treatment: A Systematic Review and Meta-analysis

  • Translational Research
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Abstract

Background

We wanted to investigate the association between circulating tumor DNA (ctDNA) detection at baseline, during and after neoadjuvant treatment, after surgery, and recurrence, in patients with nonmetastatic cancer.

Patients and Methods

In this systematic review and meta-analysis, we included studies that investigated patients undergoing neoadjuvant treatment for nonmetastatic cancer and provided recurrence indices stratified for ctDNA status at the following timepoints: baseline, during treatment, posttreatment, and postsurgery. Study quality was reported with the Newcastle–Ottawa scale, REMARK checklist, and GRADE approach. PubMed, Embase, Cochrane Library, and Web of Science were our data sources (inception to 3 June 2021). The main outcome was risk of recurrence.

Results

We identified ten studies including 727 patients with rectal, breast, gastric, and bladder cancer. All studies reported posttreatment ctDNA analysis, while seven, four, and six reported baseline, during treatment, and postsurgery ctDNA analysis, respectively. ctDNA detection was associated to recurrence across all timepoints [baseline: risk ratio (RR) 2.86, 95% confidence interval (CI) 1.33–6.14, during treatment: RR 3.81, 95% CI 2.09–6.92, posttreatment: RR 4.29, 95% CI 2.79–6.60, postsurgery: RR 8.03, 95% CI 3.16–20.43]. Heterogeneity was low to moderate.

Conclusions

This meta-analysis of observational studies found that ctDNA detection in patients undergoing neoadjuvant treatment for nonmetastatic cancer was associated with recurrence. A stronger association was evident in posttreatment and postsurgery timepoints. However, some studies reported low negative predictive value (NPV) of pathological complete response, showing that ctDNA-detection-guided escalation and de-escalation studies following neoadjuvant treatment regimens are needed before its role as a treatment guidance can be affirmed.

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Authors and Affiliations

  1. Center for Surgical Science, Zealand University Hospital Køge, Køge, Denmark

    Mikail Gögenur MD, Noor Al-Huda Hadi MS & Ismail Gögenur MD, DMSc

  2. Department of Oncology, Rigshospitalet, Copenhagen, Denmark

    Camilla Qvortrup MD, PhD

  3. Danish Colorectal Cancer Group, Copenhagen, Denmark

    Camilla Qvortrup MD, PhD, Claus Lindbjerg Andersen PhD & Ismail Gögenur MD, DMSc

  4. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

    Claus Lindbjerg Andersen PhD

  5. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Claus Lindbjerg Andersen PhD

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Contributions

Conceptualization: MG, IG; methodology: MG; software: MG; validation: NA; formal analysis: MG; investigation: MG, IG, resources: MG, NH; data curation: MG, NH; writing: original draft: MG, IG, writing: review and editing: MG, IG, NH, CQ, CA; visualization: MG, supervision: IG: project administration: MG; funding acquisition: no funding received.

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Correspondence to Mikail Gögenur MD.

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Gögenur, M., Hadi, N.AH., Qvortrup, C. et al. ctDNA for Risk of Recurrence Assessment in Patients Treated with Neoadjuvant Treatment: A Systematic Review and Meta-analysis. Ann Surg Oncol 29, 8666–8674 (2022). https://doi.org/10.1245/s10434-022-12366-7

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