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. 2025 Sep 27.
doi: 10.1002/ueg2.70112. Online ahead of print.

Real-World Molecular Testing in European Early-Onset Colorectal Cancer

Penelope V Edwards  1   2   3 , Kussai Giuma Ali Eloussta  3 , Andrew Latchford  1 , Omar Faiz  1 , Huw Thomas  1 , Filomena Liccardo  4 , Nikhil Pawa  4 , Robert Hüneburg  5   6 , Jacob Nattermann  5   6 , Andrew George  2 , Francesc Balaguer  7 , Marc Martí  8 , Antonino Spinelli  9   10 , Caterina Foppa  9   10 , Noel F F C de Miranda  11 , Irene López  12 , Elena Hurtado  13 , Fernando Jiménez  14 , Marta Jiménez-Toscano  15 , Edurne Álvaro  16 , Gonzalo Sanz  17 , Araceli Ballestero  18 , José A Rueda  19 , Cristina Viyuela  20 , Lorena Brandáriz  21 , Rosario Vidal-Tocino  22 , Damián García-Olmo  23 , Carlos Pastor  24 , Rogelio González-Sarmiento  25 , Andreana N Holowatyj  26 , Terri McVeigh  2 , José Perea  27 , Kevin J Monahan  1   3 ; Collaborators GEOCODE and SECOC Consortia
Affiliations
Free article

Real-World Molecular Testing in European Early-Onset Colorectal Cancer

Penelope V Edwards et al. United European Gastroenterol J. .
Free article

Abstract

Purpose: The global incidence and mortality of early-age onset colorectal cancer (EOCRC, or CRC diagnosed under 50 years) has increased in recent decades. High-risk surveillance and personalised oncological treatment may improve patients' outcomes. This study aims to characterise real-world somatic and germline molecular profiles in European EOCRC patients.

Patients and methods: Consecutive patients across the UK, Spain, Germany and Italy from the GEOCODE and SECOC consortia were identified using electronic patient records. Clinicopathological, somatic and germline testing data were collected on EOCRC patients. Tests included mismatch repair (MMR), somatic next generation sequencing (NGS) and germline multi-gene panels.

Results: Eight hundred ninety-three EOCRC patients were identified from 23 European centres (45.7% female, median age 42, range 14-49), predominantly in the distal colorectum: 205/893 (22.9%) patients with right-sided tumours, 302/893 (33.8%) left-sided tumours, 288/893 (32.2%) rectal tumours and 97/893 (10.8%) unknown. On somatic analysis, 735/893 (82.3%) of patients had pMMR tumours and 148/893 (16.5%) dMMR. Although 534/893 (59.7%) did not receive NGS somatic testing, somatic variants were detected in 233/359 (64.9%) of those tested. Germline variants were detected in 133/210 (63.3%) patients tested. Lynch syndrome was diagnosed in 93/210 (44.2%), of whom 17/93 (18.2%) presented with pMMR tumours. Systematic recording of family history in these real-world data was variable. In all patients with family history recorded, 153/484 (31.4%) patients reported a relative with CRC.

Conclusions: Our results support universal and paired somatic and germline multi-gene panels for all EOCRC patients, regardless of MMR status or family history. Systematic molecular testing approaches are necessary to address disparities in people with EOCRC. Larger unselected cohort studies would support validation of testing prediction models and estimates of clinically relevant variant actionability.

Keywords: colorectal cancer; early onset; germline; lynch syndrome; mismatch repair; real‐world data; somatic.

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