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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.

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. Electronic address: sabine.tejpar@uz.kuleuven.ac.be.

Annals of oncology : official journal of the European Society for Medical Oncology. 2015;(1):126-132
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Abstract

BACKGROUND 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. MATERIALS AND METHODS 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). RESULTS 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). CONCLUSIONS 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.

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Publication Type : Randomized Controlled Trial

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