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ctDNA to Guide Treatment of Colorectal Cancer: Ready for Standard of Care?

  • Lower Gastrointestinal Cancers (AB Benson, Section Editor)
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Opinion statement

Circulating tumor DNA (ctDNA) has already shown clinically relevant results in early-stage colon cancer patient management. Its prognostic value is by far much stronger than that of the available clinico-pathological biomarkers, therefore, has the potential to personalize the treatment after radical surgery through intensifying or de-intensifying the adjuvant therapy. Further developments and improvements should be pursued by (a) optimizing ctDNA assays and (b) validating its clinical utility in the different stages of this disease. Two main avenues of ctDNA testing are being pursued: tumor-informed vs tumor-agnostic assays. Two main clinical trial designs are under study: ctDNA-based strategy and ctDNA-by-treatment interaction. The former needs large sample sizes to address the main questions of the studies; thus, the target delta benefit may be the main challenge in these trial designs. The latter may be challenged by unavoidable contamination bias. To date, several clinical trials are ongoing worldwide. We believe that this large number of trials may provide an excellent common database for the demonstration of surrogacy of ctDNA for the classical 3-year disease-free survival endpoint. This would mark a huge methodological improvement to speed up new drug testing and development in the adjuvant treatment of this disease.

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Funding provided by AIRC IG 2018 to Alberto Sobrero.

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  1. Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy

    Alberto Puccini MD, Valentino Martelli MD, Alessandro Pastorino MD, Stefania Sciallero MD & Alberto Sobrero MD

  2. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132, Genoa, Italy

    Alberto Puccini MD & Valentino Martelli MD

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Alberto Puccini, Valentino Martelli, Alessandro Pastorino, and Stefania Sciallero declare no conflict of interests. Alberto Sobrero has served as consultant/advisory board member for BMS Pierre Fabre Amgen Hutchmed MSD Servier; and received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events: Roche Servier MSD BMS Amgen Merck Bayer Sanofi Pierre Fabre.

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Puccini, A., Martelli, V., Pastorino, A. et al. ctDNA to Guide Treatment of Colorectal Cancer: Ready for Standard of Care?. Curr. Treat. Options in Oncol. 24, 76–92 (2023). https://doi.org/10.1007/s11864-022-01048-x

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