Management of EaRly-onset MetastatIc cOlorectal caNcEr (ERMIONE): A single institution analysis

Despite rising incidence and mortality reported worldwide for CRC diagnosed in pts aged < 50 yrs, currently early onset metastatic CRC (EOmCRC) are treated as their older counterparts. We aimed to investigate how this specific subgroup is treated in real world.

This an observational, retrospective, monocentric study aiming to describe features, management and prognosis of EOmCRC. Pts with EOmCRC treated at our Institution between Apr2002 and Dec2022 were included. Applying a descriptive method, counts and percentages were reported for categorical variables, while median and range for continuous variables. PFS and OS were estimated with the Kaplan-Meier method. A multivariate Cox regression analysis was performed.

172 pts were included, of those 60.5% were female and 66% had an ECOG PS of 0. Median age at diagnosis was 43 yrs (range 12-49 yrs). Metastatic disease was mainly synchronous (72.1%), while only 12.2% and 15.7% were stage II and III at diagnosis and developed metachronous metastases. Primary tumor was left-sided in 70.1% . Metastasic site was most frequently liver (67.4%), followed by peritoneum (41.3%), lungs (33.7%), ovary (23.2%) and bones (9.9%). Disease was mostly widespread, while only 30.2% had a single metastatic site. MMR status was available for 87.2% of pts, being proficient in 90% and deficient in 10%. RAS/BRAF s tatus was available for 95.3% of cases, of those 47.5% was RAS/BRAF wt, 48.2% was RAS mt and 4.3% was BRAF mt. 42.4% of cases had a family history positive for cancer. Germline pathogenic or likely pathogenic variants were identified in 6.4% of cases, of those 63.6% involved MMR genes and 18.2% involved HRD genes. Median number of lines of treatment received was 2 (range 1–6). Most frequent first-line regimen was a doublet CT (69.8%), followed by a triplet CT (23.8%) and immunotherapy (4.1%), CT regimens were associated to bevacizumab in 45.3% of cases and to antiEGFRs in 29.1% of cases. Throughout the whole continuum of care 8.7% of pts received immunotherapy and 21.5% received treatment within a clinical trial. 70.3% of pts received surgery and/or local ablative treatments (LATs) with radical intent (52.9% surgery, 12.2 both, 4.6% LATs). At a median FU of 38.6 m, mPFS for first-line was 13.5 m (95%CI 12.1-15.0 m) and mOS was 41.5 m (95%CI 33.9 - 44.1 m). Median OS was significantly longer for pts who received surgery and/or LATs compared to those who did not (43.4 vs 23.6 m, p p= .0007), BRAF status ( p= .0165) and ECOG PS ( p= .0209) independently correlated with OS.

We confirmed that EOmCRC is more frequently diagnosed as synchronous disease, due to delayed diagnosis. Despite the small population and the retrospective nature, we showed that combining surgery and/or LATs to systemic therapy is associated with increased OS in EOmCRC. These evidence warrant further validation in prospective setting.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.