3291 - Microsatellite Instability (MSI) status and prognosis in colorectal cancer: meta-analysis

Background

Microsatellite instability (MSI) is thought to be a marker of immunogenicity and better prognosis in colorectal cancer (CRC). However, the mechanism by which MSI confers a survival advantage is not well known and there is a range of results reported in the literature.

Methods

A systematic literature search of original studies was performed on Ovid searching Medline, Embase, Cochrane Library, CINAHL, Clinical Trials databases from inception of database to current. Data extracted included age, stage, MSI-H, MSS and MSI-L, proximal (right) vs. distal (left), colon vs. rectal, BRAF status, type of MSI or IHC test used, incidence of Lynch within cohort. The primary endpoint was survival (overall survival (OS), disease/relapse free survival (DFS) and disease (cancer) specific survival DSS). Statistical analysis was performed using RevMan Ver 5.3 Cochrane Collaboration.

Results

From 11,747 studies, 117 met the inclusion criteria (n = 100,257; MSI-H n = 12,263, (MSI-H 12.2%). Overall, MSI was associated with improved OS (OR 0.80 (0.71, 0.91). When stratified by stage, there was no difference in OS in stage I and IV, but a protective effect in stage II (OR 0.69 (0.51, 0.92)) and III (0.70 (0.54, 0.91)) CRC. By age, there was benefit in studies where reported median age < 60 (OR 0.66 (0.54,0.82)) but not ≥ 60. There was no difference in OS between MSI-L and MSS. In studies including only mucinous/signet cell/poor differentiation, there was no difference in OS. In both right and left colon, MSI status was associated with improved OS, but not in the rectum. MSI status was associated with improved DFS (HR 0.75 (0.66, 0.84)), but there was no difference in DSS (HR 0.78 (0.60, 1.03)), and this was seen in all stages (I-IV).

Conclusions

MSI is associated with improved overall survival in stage II and III colorectal cancer. Improved prognosis is seen in younger patients, in both right and left sided colon cancer, but evidence is limited in rectal cancer. MSI was associated with less relapse, but was not associated with cancer specific survival at any stage.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.