Prognosis of stage II and III colon carcinoma treated with adjuvant 5-FU or FOLFIRI in relation to microsatellite status, results of the PETACC-3 trial
Menée à partir de l'analyse de tissus tumoraux prélevés sur 1 254 patients atteints d'un carcinome du côlon de stade II ou III traité par chimiothérapie à base de 5-fluorouracile/leucovorine ou par chimiothérapie de type FOLFIRI, cette étude évalue, en fonction du niveau de stabilité des microsatellites, la survie sans récidive ou la survie globale des patients
Background : Although microsatellite instable (MSI) colon carcinoma (CC) 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-FU/LV 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 3 or more loci were unstable and MSS otherwise. Study endpoints 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 HR 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 but 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 MS-L/S patients and adding irinotecan has no added benefit.
Annals of Oncology , résumé, 2014