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Multicenter Study
. 2025 Feb;132(2):188-194.
doi: 10.1038/s41416-024-02902-5. Epub 2024 Nov 27.

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

Andrea Pretta  1 , Pina Ziranu  2 , Eleonora Perissinotto  3   4 , Filippo Ghelardi  5 , Federica Marmorino  6   7 , Riccardo Giampieri  8   9 , Mariangela Puci  10 , Maria Caterina De Grandis  3   4 , Eleonora Lai  2 , Vincenzo Nasca  5 , Paolo Ciraci  6   7 , Marco Puzzoni  2 , Krisida Cerma  3 , Carolina Sciortino  5 , Ada Taravella  6   7 , Gianluca Pretta  11 , Lorenzo Giuliani  8   9 , Camilla Damonte  5 , Valeria Pusceddu  2 , Giovanni Sotgiu  10 , Rossana Berardi  8   9 , Sara Lonardi  3 , Francesca Bergamo  3 , Filippo Pietrantonio  5 , Chiara Cremolini  6   7 , Mario Scartozzi  2
Affiliations
Multicenter Study

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

Andrea Pretta et al. Br J Cancer. 2025 Feb.

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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Conflict of interest statement

Competing interests: The authors declare no competing interests. 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.

Figures

Fig. 1
Fig. 1
Patients characteristics.
Fig. 2
Fig. 2
Pie charts. Molecular profile distribution in LO-CRCs and EO-CRCs patients.
Fig. 3
Fig. 3. Kaplan–Meier curves for EO-CRC and LO-CRC, overall population.
a Overall survival and b progression-free survival in the overall population.
Fig. 4
Fig. 4. Kaplan–Meier curves for EO-CRC and LO-CRC, RAS and BRAF wild-type population.
a Overall survival and b progression-free survival in the wild-type population.
Fig. 5
Fig. 5. Kaplan–Meier curves for EO-CRC and LO-CRC, RAS/BRAS mutated population.
a Overall survival and b progression-free survival in the RAS/BRAF mutated population.
Fig. 6
Fig. 6. Kaplan–Meier curves for EO-CRC and LO-CRC, BRAF V600E mutated population.
a Overall survival and b progression-free survival in the BRAF V600E mut population.
See this image and copyright information in PMC

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