结直肠癌中微卫星不稳定性作为预后因素的竞争风险分析。

Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer.

机构信息

Department of Colorectal Surgery, University of Sydney, Sydney, New South Wales, Australia.

Medical Oncology Group, Ingham Institute of Applied Medical Research, University of Sydney, Sydney, New South Wales, Australia.

出版信息

Br J Surg. 2017 Aug;104(9):1250-1259. doi: 10.1002/bjs.10542. Epub 2017 Apr 12.

DOI:10.1002/bjs.10542

PMID:28401534

Abstract

BACKGROUND

Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk.

METHODS

A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods.

RESULTS

Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections.

CONCLUSION

Microsatellite instability status was not an independent prognostic variable in these patients.

摘要

背景

尽管大量文献表明高度微卫星不稳定性（MSI-H）可提高结直肠癌切除术后的生存率并预防复发，但由于许多研究仅显示出微弱的双变量关联或与结局无多变量关联，因此这种效果仍存在争议。本研究通过调整因其他原因导致的死亡作为竞争风险，来检验 MSI 状态与结直肠癌结局之间的关系。

方法

对接受结直肠癌切除术的患者的医院数据库进行了临床、手术、病理、辅助治疗和随访信息的查询。通过免疫组化检测错配修复蛋白缺陷来确定 MSI-H 状态。通过竞争风险方法评估复发和结直肠癌特异性死亡的累积发生率。

结果

在 2002 年 8 月至 2008 年 12 月间接受手术且随访至 2013 年 12 月至少 1 年的 1009 例患者中，有 114 例（11.3%）为 MSI-H（70 岁及以上者占 72.8%；女性占 63.2%）。在经过潜在治愈性切除后，在调整非结直肠癌死亡作为竞争风险以及调整 22 个临床、手术和病理变量后，MSI-H 与复发（风险比（HR）0.81，95%置信区间（CI）0.42 至 1.57）或结直肠癌特异性死亡（HR 0.73，0.39 至 1.35）之间在该患者人群中无关联。对于姑息性切除术，MSI-H 与结直肠癌特异性死亡之间无关联（HR 0.65，0.21 至 2.04）。MSI-H 与根治性（HR 1.55，1.04 至 2.30）和姑息性（HR 3.80，1.32 至 11.00）切除术后的非结直肠癌死亡均相关。