SIDEBAR: Is Microsatellite Instability Status also Predictive in Stage II Disease?


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“Microsatellite instability status is a validated prognostic marker in stage II colorectal cancer. It is the strongest prognostic marker we have in that group,” Dr. Overman commented. “The fact is that we should be getting this [test] consistently to help us make this discussion [of prognosis] easier.”

Recent data further suggest that microsatellite instability status may also predict benefit from therapy or lack thereof. An initial report suggested that patients with microsatellite instability–high status (indicating deficient mismatch repair) and stage II or III disease universally do not derive progression-free survival benefit from adjuvant fluorouracil (5FU) chemotherapy.1

However, an update of the same data set suggested that the issue is more complex, with variation according to the origin of the microsatellite instability–high status.2 Specifically, patients with germline origin (mainly younger patients with hereditary nonpolyposis colorectal cancer, a family history, and genetically driven microsatellite instability–high status) did appear to benefit. But patients with sporadic origin (mainly older patients with methylation of the MLH1 gene) did not.

“So I think this predictive issue [for lack of 5-FU benefit] is a little more complex. It really appears to be limited to sporadic [microsatellite instability]–high status,” Dr. Overman concluded. “It would be nice to actually have some confirmatory data that give us a final answer.” ■

Disclosure: Dr. Overman has received research support from Amgen, Roche, and Bristol-Myers Squibb; and is on the advisory board and lectures for Sanofi-Aventis and Roche.

References

1. Sargent DJ, Marsoni S, Monges G, et al: Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219-3226, 2010.

2. Sinicrope FA, Foster NR, Thibodeau SN, et al: DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst 103:863-875, 2011.


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