Abstract 84P
Background
It is widely recognised that the incidence of early-onset colorectal cancer, commonly defined as aged under 50, is increasing. Although some observational studies have described those aged under 50 as a uniquely aggressive phenotype, this has not been consistently observed. It is possible a younger age bracket more accurately isolates a distinct group.
Methods
We extracted prospectively collected data from consecutive metastatic colorectal cancer (mCRC) patients on the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australasian registry. We compared the demographic and clinicopathologic characteristics of very young patients (VYP < 35 years at diagnosis), young patients (YP 35-49 years) and older patients (OP ≥ 50 years).
Results
4405 mCRC patients were identified from July 2009 - March 2024; 139 (3.2%) VYP, 539 (12%) YP, 3727 (84%) OP. VYP had similar rates of ECOG PS 0-1 to YP (97% vs 95%, p=0.41) but improved ECOG compared to OP (97% vs 82%, p<0.001). More VYP had de novo metastatic disease (VYP=79%, YP=70%, OP=58%, p=0.03 and p<0.001, respectively). Similar proportions had left sided primary tumours (VYP=67%, YP=72%, OP=63%, p=0.21 and p=0.33, respectively). After widespread adoption of molecular testing in 2015, BRAF V600E mutations were more common in VYP (36%) compared to YP (11%, p<0.001) and OP (13%, p<0.001). Deficient MMR tumours were increased in the VYP (VYP=9.1%, YP=3.1%, OP=6.7%, p=0.03 and p=0.54, respectively). VYP and YP were similarly likely to receive chemotherapy (94% vs 92%, p=0.65), and FOLFOXIRI (17% vs 13%, respectively, p=0.23). Median OS was similar for VYP and YP (29m vs 34.2m, HR 0.895, 95%CI 0.69-1.16, p=0.40). Table: 84P
Molecular data and testing rates since 2015
| Variable | YP (N=382) | VYP (N=102) | OP (N=2293) | p-value (VYP vs YP) | p-value (VY vs OP) | |
| MSI ustable/ MMR deficiency | N (%) | 11 (3.1) | 8 (9.1) | 120 (6.7) | 0.03 | 0.54 |
| Testing rate, % | 92 | 86 | 78 | |||
| BRAF V600E mutation | N (%) | 36 (11) | 30 (36) | 210 (13) | <0.001 | <0.001 |
| Testing rate, % | 86 | 82 | 71 | |||
| BRAF mutation and pMMR | N (%) | 35 (11) | 26 (32) | 139 (8.7) | <0.001 | <0.001 |
| Testing rate, % | 86 | 80 | 70 | |||
| RAS mutation | N (%) | 172 (50) | 33 (38) | 881 (49) | 0.05 | 0.05 |
| Testing rate, % | 90 | 84 | 78 |
Conclusions
In our analysis, patients aged under 35 years appear to represent a distinct subset of early onset mCRC, with increased rates of synchronous disease, BRAFmt and dMMR cancers compared versus those aged 35-50 at presentation. There were no significant differences in survival outcomes for VYP and YP.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Personalised Oncology, Walter and Eliza Hall Institute.
Funding
Has not received any funding.
Disclosure
N. Rainey: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Honoraria: Eli Lilley, Gilead; Financial Interests, Personal, Other, Travel: Pfizer. V. Wong: Financial Interests, Personal, Other, Travel: Merck, Novartis. P. Gibbs: Financial Interests, Personal, Other, Honoraria: Amgen, BMS, Foundation Medicine, Guardant, Haystack Oncology, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Servier, Takeda. All other authors have declared no conflicts of interest.