MSI Status Shows No Effect on Metastatic Colorectal Cancer Prognosis

Microsatellite instability (MSI) status appeared to have no association with outcomes in patients with liver metastases that spread from colorectal cancer (CRC), according to results from an international, multi-institutional analysis presented at the 2018 Gastrointestinal Cancers Symposium.

When DNA replicates and divides, there can be some errors in the copies of the genetic material. MSI-H status is a result of when genes that regulate DNA, also known as mismatch repair genes, do not work properly in correcting errors in DNA as cells divide.

Previous research has shown that MSI status is associated with a favorable prognosis and response to chemotherapy and immunotherapy in patients with non-metastatic colorectal cancer (CRC). Adversely, other studies found that MSI status may have a minimal impact on patients with metastatic disease.

“We know that initial stages of CRC that is nonmetastatic when MSI is present is associated with a better prognosis because those patients can respond better to specific therapies than patients that do not have those genetic features or biomarkers,” Federico Aucejo, M.D., from the Department of General Surgery at the Cleveland Clinic, said in an interview with CURE.

“We do not know what the real impact is in outcomes of MSI in patients who have developed metastatic disease, specifically to the liver.”

Therefore, Aucejo and colleagues evaluated whether MSI status can be a prognostic factor for a subset of patients with resectable colorectal liver metastases. They identified 332 patients who underwent curative-intent resection between 2003 and 2017 in five participating tertiary centers in the U.S. and Europe and had available data on MSI status.

Only 16 patients were MSI-positive (5 percent). The majority of patients were male (59.6 percent), had rectal primary tumors (40.7 percent), had T3 tumors (61.3 percent), and had lymph node metastases present (64.5 percent). Patients had at least one liver lesion, and tumor diameter was approximately 2 cm on average. Lastly, the majority of patients underwent preoperative chemotherapy administration (68.8 percent).

Baseline characteristics appeared similar among patients who were MSI-positive or -negative.

After a median follow-up of 22.1 months, 154 patients experienced disease recurrence (47.5 percent) and 70 patients died (21.1 percent). MSI status was not associated with disease-free survival and overall survival.

Aucejo acknowledged the study was limited by the small sample size of patients with MSI tumors. However, the researchers noted additional research in larger cohorts from additional participating institutions is currently underway to assess these preliminary findings.

“This conclusion warrants further investigation through larger cohorts of patients — including more diverse populations and ethnicities and different countries,” added Aucejo.

Although no associated were found in this study, the possibilities of evaluating genetic biomarkers in CRC are endless. “The final message would be that these efforts of understanding the impact of genetic tumor signatures in patient outcomes definitively has a future,” Aucejo said. “Patients need to understand that that is what they should expect to see moving forward — that the oncologists and surgeons will look more and more in to genetic biomarkers in tumors.”