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Ann Oncol. 2015 Jan;26(1):126-32. doi: 10.1093/annonc/mdu499. Epub 2014 Oct 30.

Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial.

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SAKK Swiss Group for Clinical Cancer Research, Coordinating Center, Bern SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Laboratory of Tumor Cell Biology School of Medicine, University of Crete, Heraklion, Greece Center for Human Genetics O&N1, Katholieke Universiteit Leuven, Leuven, Belgium.
Oncosurgery Unit, Geneva University Hospital, Geneva.
Department of Pathology, Lausanne University, Lausanne.
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland Ludwig Center for Cancer Research Department of Oncology, University of Lausanne, Lausanne, Switzerland.
Center for Human Genetics O&N1, Katholieke Universiteit Leuven, Leuven, Belgium Laboratory of Molecular Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium



Although colon cancer (CC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CC, the impact varies according to clinicopathological parameters. We studied how MSI status affects prognosis in a trial-based cohort of stage II and III CC patients treated with 5-fluorouracil (5-FU)/leucovorin or FOLFIRI.


Tissue specimens of 1254 patients were tested for 10 different loci and were classified as MSI-high (MSI-H) when three or more loci were unstable and MSS otherwise. Study end points were overall survival (OS) and relapse-free survival (RFS).


In stage II, RFS and OS were better for patients with MSI-H than with MSS CC [hazard ratio (HR) 0.26, 95% CI 0.10-0.65, P = 0.004 and 0.16, 95% CI 0.04-0.64, P = 0.01). In stage III, RFS was slightly better for patients with MSI-H CC (HR 0.67, 95% CI 0.46-0.99, P = 0.04), but the difference was not statistically significant for OS (HR 0.70, 95% CI 0.44-1.09, P = 0.11). Outcomes for patients with MSI-H CC were not different between the two treatment arms. RFS was better for patients with MSI-H than with MSS CC in the right and left colon, whereas for OS this was significant only in the right colon. For patients with KRAS- and BRAF-mutated CC, but not for double wild-type patients, RFS and OS were significantly better when the tumors were also MSI-H. An interaction test was statistically significant for KRAS and MSI status (P = 0.005), but not for BRAF status (P = 0.14).


Our results confirm that for patients with stage II CC but less so for those with stage III MSI-H is strongly prognostic for RFS and OS. In the presence of 5-FU treatment, stage II patients with MSI-H tumors maintain their survival advantage in comparison with MSS patients and adding irinotecan has no added benefit. CLINICALTRIALS.GOV IDENTIFIER: NCT00026273.


adjuvant treatment; colon cancer; microsatellite instability; survival; translational research

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