Management of Early-onset Metastatic Colorectal Cancer (ERMIONE): A single institution analysis.
Authors: Valente Giustina , Di Bello Armando , Anghelone Annunziato , Schietroma Francesco , Beccia Viria , Caira Giulia , Spring Alexia , Trovato Giovanni , Ceccarelli Anna , Chiofalo Laura , Perazzo Serena , Bensi Maria , Basso Michele , Pozzo Carmelo , Salvatore Lisa , Calegari Maria Alessandra , Tortora Giampaolo 
Published: June 2023

3593 Background: 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. Methods: 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. Results: 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%. Metastatic 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 status 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 < .0001). At multivariate analysis, besides surgery and/or LATs (p= .0007), BRAF status (p= .0165) and ECOG PS (p= .0209) independently correlated with OS. Conclusions: 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.