Abstract 129P
Background
Microsatellites instability (MSI) is a consequence of a DNA dMMR system and occurs in 20% of non-metastatic and 5% in metastatic CC. Lynch syndrome (LS) accounts for about a quarter of MSI CCs. MSI status has both predictive and prognostic value, although the role of adjuvant chemotherapy (aCT) has yet to be fully understood. We evaluated a real-world large cohort of dMMR/MSI CC patients.
Methods
This is a retrospective observational study on consecutive CC cases tested by immunohistochemistry for dMMR referred to the Pathological Unit at Humanitas Research Hospital from January 2016 to July 2023. Clinico-pathological, molecular features and outcome data were collected.
Results
Overall, 382 dMMR CC were included. 59% were female. Median age was 74 (range 31-91). The majority was in stage II (52%) and I (23%); 20% and 5% were stage III and IV, respectively. Regarding sidedness, 77% were right-sided, 14% transverse and 7% left-sided. 87% of the dMMR CC showed loss of MLH1/PMS2, while MSH2/MSH6 loss was found in 6% of cases. Out of 179 patients tested, 53% showed BRAF V600E mutation, 10% harbored KRAS mutation, 17% presented PI3KCA mutation. LS was diagnosed in 15% of patients. Overall, 321 patients were followed up at our center and 13% received aCT. At a median follow up of 31 months (range 0.2-90.3), the disease-free survival (DFS) at 3 years was 79%, irrespective of adjuvant treatment. As for the stage-specific analysis, 3-year DFS was 85% for stage II and 54% for stage III, showing a statistically significant difference in DFS among stage III patients who received double-agent aCT compared to those who did not with a 3-year DFS of 70% and 41%, respectively (p=0.030). No statistically significant difference in 3-year DFS for patients in stage II was detected based on adjuvant treatments (p=0.262), nor for stage II high-risk patients - pT4N0 (p=0.896). No significant relationship was found between molecular alterations and outcomes.
Conclusions
We observed that oxaliplatin-based aCT remains effective in stage III, while no benefit has been shown in stage II, although these findings should be interpreted with caution due to small sample size. Neither predictive nor prognostic molecular biomarkers were detected.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.