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Clinical Studies

Early onset metastatic colorectal cancer patients as a distinctive clinical and molecular phenomenon

British Journal of Cancer volume 132, pages 188–194 (2025)Cite this article

Subjects

Abstract

Background

Despite a reduction of both incidence and mortality from CRC, recent studies have shown an increase in the incidence of early-onset CRC (EO-CRC). Data on this setting are limited. The aim of our study was to evaluate the clinical and molecular profiles of metastatic EO-CRC patients in order to identify differences compared to a late-onset CRC (LO-CRC) control group.

Methods

We retrospectively collected data from 1272 metastatic colorectal cancers from 5 different Italian Institutions. The main objective was to the evaluate clinical outcome for EO-CRC patients in comparison to patients included in the control group.

Results

In the overall population, mOS was 34,7 in EO-CRC pts vs 43,0 months (mo) (p < 0,0001). In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 30,3 vs 34,0 mo (p = 0,0156). In RAS/BRAF wild-type EO-CRC mOS was 43,0 vs 50,0 mo (p = 0,0290). mPFS was 11,0 in EO-CRC pts vs 14,0 mo (p < 0,0001).

Conclusion

Findings indicate a general worse prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly this seems to occur regardless of the molecular status. These observations might have a considerable impact on clinical practice and research.

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Fig. 1
Fig. 2
Fig. 3: Kaplan–Meier curves for EO-CRC and LO-CRC, overall population.
Fig. 4: Kaplan–Meier curves for EO-CRC and LO-CRC, RAS and BRAF wild-type population.
Fig. 5: Kaplan–Meier curves for EO-CRC and LO-CRC, RAS/BRAS mutated population.
Fig. 6: Kaplan–Meier curves for EO-CRC and LO-CRC, BRAF V600E mutated population.

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Data availability

Datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy

    Andrea Pretta, Pina Ziranu, Eleonora Lai, Marco Puzzoni, Valeria Pusceddu & Mario Scartozzi

  2. Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy

    Eleonora Perissinotto, Maria Caterina De Grandis, Krisida Cerma, Sara Lonardi & Francesca Bergamo

  3. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

    Eleonora Perissinotto & Maria Caterina De Grandis

  4. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo Ghelardi, Vincenzo Nasca, Carolina Sciortino, Camilla Damonte & Filippo Pietrantonio

  5. Unit of Oncology, University Hospital of Pisa, Pisa, Italy

    Federica Marmorino, Paolo Ciraci, Ada Taravella & Chiara Cremolini

  6. Department of Translational Research & New Technologies in Medicine & Surgery, University of Pisa, Pisa, Italy

    Federica Marmorino, Paolo Ciraci, Ada Taravella & Chiara Cremolini

  7. Clinica Oncologica - Dipartimento Scienze Cliniche e Molecolari - Università Politecnica delle Marche, Ancona, Italy

    Riccardo Giampieri, Lorenzo Giuliani & Rossana Berardi

  8. Azienda Ospedaliero Universitaria delle Marche – Ancona, Ancona, Italy

    Riccardo Giampieri, Lorenzo Giuliani & Rossana Berardi

  9. Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Sardinia, Italy

    Mariangela Puci & Giovanni Sotgiu

  10. Science department, King’s School Hove, Hangleton, East Sussex, UK

    Gianluca Pretta

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Contributions

Andrea Pretta: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Resources, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization. Pina Ziranu: Resources, Data Curation, Formal analysis, Writing - Original Draft, Writing - Review & Editing. Eleonora Perissinotto: Resources, Data Curation. Filippo Ghelardi: Resources, Data Curation. Federica Marmorino: Resources, Data Curation. Riccardo Giampieri: Resources, Data Curation, Formal analysis, Writing - Original Draft, Writing - Review & Editing. Mariangela Puci: Data Curation, Formal analysis. Maria Caterina De Grandis: Resources, Data Curation. Eleonora Lai: Resources. Vincenzo Nasca: Resources, Data Curation. Paolo Ciracì: Resources, Data Curation. Marco Puzzoni: Resources. Krisida Cerma: Resources. Data Curation. Carolina Sciortino: Resources, Data Curation. Ada Taravella: Resources, Data Curation. Gianluca Pretta: Writing - Review & Editing. Lorenzo Giuliani: Resources, Data Curation. Camilla Damonte: Resources, Data Curation. Valeria Pusceddu: Resources, Data Curation. Giovanni Sotgiu: Data Curation, Formal analysis. Rossana Berardi: Resources. Sara Lonardi: Resources, Data Curation. Francesca Bergamo: Resources, Data Curation. Filippo Pietrantonio: Resources, Data Curation. Chiara Cremolini: Resources, Data Curation. Mario Scartozzi: Methodology, Validation, Formal analysis, Resources, Data Curation, Writing - Original Draft, Writing - Review & Editing.

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Correspondence to Andrea Pretta.

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Ethics approval and consent to participate

Ethics Committee approval was obtained for the study (Protocol number 2020/10912 – code: EMIBIOCCOR) from Cagliari Indipendent Ethics Committee and written informed consent was obtained from all participants for their tissues to be utilized for this work. This study was performed in accordance with the study protocol, the ethical principles stated in the Declaration of Helsinki as well as those indicated in the International Conference on Harmonization (ICH) Note for Guidance on Good Clinical Practice (GCP; ICH E6, 1995), and all applicable regulatory requirements.

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Pretta, A., Ziranu, P., Perissinotto, E. et al. Early onset metastatic colorectal cancer patients as a distinctive clinical and molecular phenomenon. Br J Cancer 132, 188–194 (2025). https://doi.org/10.1038/s41416-024-02902-5

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