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  • Perspective
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Personalizing adjuvant therapy for patients with colorectal cancer

Nature Reviews Clinical Oncology volume 21, pages 67–79 (2024)Cite this article

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Abstract

The current standard-of-care adjuvant treatment for patients with colorectal cancer (CRC) comprises a fluoropyrimidine (5-fluorouracil or capecitabine) as a single agent or in combination with oxaliplatin, for either 3 or 6 months. Selection of therapy depends on conventional histopathological staging procedures, which constitute a blunt tool for patient stratification. Given the relatively marginal survival benefits that patients can derive from adjuvant treatment, improving the safety of chemotherapy regimens and identifying patients most likely to benefit from them is an area of unmet need. Patient stratification should enable distinguishing those at low risk of recurrence and a high chance of cure by surgery from those at higher risk of recurrence who would derive greater absolute benefits from chemotherapy. To this end, genetic analyses have led to the discovery of germline determinants of toxicity from fluoropyrimidines, the identification of patients at high risk of life-threatening toxicity, and enabling dose modulation to improve safety. Thus far, results from analyses of resected tissue to identify mutational or transcriptomic signatures with value as prognostic biomarkers have been rather disappointing. In the past few years, the application of artificial intelligence-driven models to digital images of resected tissue has identified potentially useful algorithms that stratify patients into distinct prognostic groups. Similarly, liquid biopsy approaches involving measurements of circulating tumour DNA after surgery are additionally useful tools to identify patients at high and low risk of tumour recurrence. In this Perspective, we provide an overview of the current landscape of adjuvant therapy for patients with CRC and discuss how new technologies will enable better personalization of therapy in this setting.

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Fig. 1: Factors that potentially affect prognosis of colorectal cancer.
Fig. 2: Combination of digital biomarker and conventional histopathological prognostic indices.
Fig. 3: Combination of tissue-based biomarkers and ctDNA to improve patient management.

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Acknowledgements

The authors thank M. Seiergren (Oslo University Hospital) for help with creating the figures and acknowledge funding from the Chinese Science Council (to L.Y. and J.Y.) and The Norwegian Research Council (project number 334862, to A.K., H.E.D. and D.J.K.). We wish also to acknowledge the remarkable scientific contribution and leadership of our dear friend, colleague and coauthor H. Danielsen, who died recently.

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Author notes

  1. These authors contributed equally: Li Yang, Jinlin Yang.

  2. Deceased: Håvard E. Danielsen.

Authors and Affiliations

  1. Department of Gastroenterology, Sichuan University, Chengdu, China

    Li Yang & Jinlin Yang

  2. Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway

    Andreas Kleppe & Håvard E. Danielsen

  3. Department of Informatics, University of Oslo, Oslo, Norway

    Andreas Kleppe

  4. Centre for Research-based Innovation Visual Intelligence, UiT The Arctic University of Norway, Tromsø, Norway

    Andreas Kleppe

  5. Radcliffe Department of Medicine, Oxford University, Oxford, UK

    Håvard E. Danielsen & David J. Kerr

Authors
  1. Li Yang
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  2. Jinlin Yang
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  3. Andreas Kleppe
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  4. Håvard E. Danielsen
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  5. David J. Kerr
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Contributions

All the authors researched data for the article, contributed substantially to discussion of the content and wrote the manuscript. L.Y., A.K., H.E.D. and D.J.K. reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to David J. Kerr.

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Competing interests

H.E.D. reports filing a patent application entitled “Histological image analysis” with International Patent Application Number PCT/EP2018/080828. A.K. and H.E.D. report filing a patent application entitled “Histological image analysis” with International Patent Application Number PCT/EP2020/076090. A.K., H.E.D. and D.J.K. are founders of DoMore Diagnostics. D.J.K. is a founder of Oxford Cancer Biomarkers. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks T. Yoshino and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Yang, L., Yang, J., Kleppe, A. et al. Personalizing adjuvant therapy for patients with colorectal cancer. Nat Rev Clin Oncol 21, 67–79 (2024). https://doi.org/10.1038/s41571-023-00834-2

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