Abstract 13P
Background
While clinicopathologic risk factors for recurrence in colorectal cancer have been described, data on genetic risk factors for recurrence are limited. This study aimed to identify tumor mutations associated with recurrence after resection of node-negative colorectal adenocarcinoma.
Methods
Patients with T1-3, N0, M0 colorectal adenocarcinoma who underwent surgery and whole exome sequencing of the primary tumor with documented clinical follow-up were identified in cBioPortal. Demographic, clinicopathologic variables, genomics, and outcomes were retrospectively analyzed. Genes mutated in >15% of tumors in either the recurrent or disease-free cohort were included in a multivariate logistic regression to determine their prognostic significance.
Results
357 total patients were included, of whom 58 (16%) recurred and 299 (834%) were disease free. There were no significant differences in age, sex, tumor site, or tumor mutation burden between groups, however there were more T3 tumors in the recurrence group (84%% vs 63%; p-0.005). Median follow-up was 36 months and median time-to-recurrence was 16 months. On multivariate logistic regression, 4 mutated genes – NALCN, BCL9, SIPA1L1, PIK3CA- were found to be associated with recurrence (Table). Of these, NALCN, SIPA1L1 and BCL9 were specifically associated with early recurrence (<16 months). Table: 13P
Multivariate logistic regression: Risk of recurrence
| Characteristic | OR 1 , 2 | 95% CI 1 | p-value |
| T Stage | |||
| T1 | --- | ||
| T2 | 0.66 | 0.14, 4.82 | 0.6 |
| T3 | 2.74 | 0.77, 17.5 | 0.2 |
| NALCN | 3.72 | 1.58, 8.80 | 0.003 |
| BCL9 | 3.52 | 1.30, 9.31 | 0.011 |
| SIPA1L1 | 4.89 | 1.56, 16.5 | 0.007 |
| PIK3CA | 1.99 | 1.01,3.85 | 0.043 |
1OR = Odds Ratio, CI = Confidence Interval
2Adjusted for Age, T Stage, Site, TMB-H
Conclusions
Our study identifies a set of mutated genes which confer increased risk for recurrence independent of T stage after surgical resection in Stage I-II colorectal cancer. Together with clinicopathologic factors, these mutations may help identify patients who benefit from adjuvant chemotherapy or increased surveillance. While the role of PIK3CA in colon cancer is recognized, further research is warranted into the role of NALCN, SIPA1L1 and BCL9 in early metastatic spread.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Pigazzi: Non-Financial Interests, Personal, Advisory Role, Consulting: Ethicon; Non-Financial Interests, Personal, Advisory Role, Consultant: Medtronic; Financial Interests, Personal, Ownership Interest: Xodus Medical. M.D. Jafari: Non-Financial Interests, Personal, Advisory Role, Consultant: Medtronic. All other authors have declared no conflicts of interest.