ctDNA on liquid biopsy for predicting response and prognosis in locally advanced rectal cancer: A systematic review

Abstract

Background: The management of locally advanced rectal cancer (LARC) requires a multidisciplinary approach, with an increasing interest for non-operative strategies. Liquid biopsy for obtaining circulating tumor DNA (ctDNA) can provide information on neoadjuvant chemoradiotherapy (nCRT) pathological response and cancer-specific prognosis, and therefore might be a promising guide for these treatments.

Methods: A systematic review of the studies available in literature has been performed to assess the role of ctDNA as a predictive and prognostic biomarker in LARC patients.

Results: We retrieved 21 publications, of which 17 full-text articles and 4 abstracts. Results have been labelled into two groups: predictive and prognostic. Data about the usefulness of liquid biopsy in this setting is still inconclusive. However, baseline higher levels of longer fragments of cell-free DNA and integrity index, tumor-specific mutations and certain methylated genes could predict non-responders. Also, undetectable baseline ctDNA and decrease of common rectal cancer mutations throughout treatment (dynamic monitoring) were predictive factors of pathological complete response. The continuous detection of ctDNA in different timepoints of treatment (minimal residual disease) was consistently associated with worse prognosis.

Conclusions: ctDNA is a promising biomarker that could assist predicting treatment response to nCRT and prognosis in patients with LARC. The ideal methods and timings for the liquid biopsy still have to be defined.

Keywords: Chemoradiotherapy; Circulating-tumor DNA; Liquid biopsy; Rectal cancer.