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
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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DOI：
10.1093/annonc/mdu499
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发表时间：
2015-01-01
影响因子：
50.5
通讯作者：
Tejpar, S.
中科院分区：
文献类型：
--
作者：
Klingbiel, D.;Saridaki, Z.;Tejpar, S.
尽管微卫星不稳定性（MSI）的结肠癌（CC）比微卫星稳定性（MSS）的CC具有更有利的预后，但其影响因临床病理参数而异。我们研究了MSI状态如何影响II期和III期CC患者的预后，这些患者接受了5-氟尿嘧啶（5-FU）/亚叶酸或FOLFIRI治疗，1254例患者的组织标本检测了10个不同的基因座，当3个或3个以上的基因座不稳定时被归类为MSI高（MSI-H），否则归类为MSS。研究终点为总生存期（OS）和无复发生存期（RFS），在II期，MSI-H患者的RFS和OS优于MSS CC患者[风险比（HR）0.26，95%CI 0.10-0.65，P = 0.004和0.16，95%CI 0.04-0.64，P = 0.01]。在III期，MSI-H CC患者的RFS略好（HR 0.67，95% CI 0.46-0.99，P = 0.04），但OS差异无统计学意义（HR 0.70，95% CI 0.44-1.09，P = 0.11）。两个治疗组之间MSI-H CC患者的结局无差异。在右结肠和左结肠中，MSI-H患者的RFS优于MSS CC患者，而对于OS，仅在右结肠中具有显著性。对于KRAS和BRAF突变的CC患者，而不是双野生型患者，当肿瘤也是MSI-H时，RFS和OS显著更好。KRAS和MSI状态的相互作用检验具有统计学意义（P = 0.005），但不适用于BRAF状态（P = 0.14）。我们的结果证实，对于II期CC患者，但对于III期MSI-H患者，RFS和OS的预后较好。在5-FU治疗的情况下，与MSS患者相比，患有MSI-H肿瘤的II期患者保持了其生存优势，并且添加伊立替康没有额外的益处。
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.