Internal Medicine, St Thomas' Hospital, London, United Kingdom.
Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, United Kingdom.
Int J Colorectal Dis. 2022 Jan;37(1):35-46. doi: 10.1007/s00384-021-04046-x. Epub 2021 Oct 22.
Colorectal cancer (CRC) can be classified according to the chromosomal-instability pathway (a microsatellite-stable (MSS) pathway) and the microsatellite-instability (MSI) pathway. Adjuvant therapy after surgery in advanced CRC is usually based on fluoropyrimidine 5-fluorouracil (5-FU) alone or combined with other agents. Controversy however remains on the use of 5-FU-based regimens in treating MSI-related tumours.
To systematically investigate the relationship between tumour microsatellite profile and 5-year overall survival in patients with CRC treated with 5-FU.
A systematic literature review of PubMed and Embase databases was conducted. Pre-specified criteria determined study inclusion/exclusion. The PRISMA and QUADAS-2 criteria were used to assess study suitability and quality respectively. Patients were categorised as having either MSI or MSS CRC. Overall 5-year survival was estimated from Kaplan-Meier curves. Publication bias was assessed using funnel-plots and Egger's test.
1807 studies were identified, with meta-analysis performed using nine studies. 5-FU treated individuals with CRC who died at 5 years were found to be 0.31 times less likely to have MSI than those who were alive, although this was not statistically significant. There was an insufficient number of studies to enable subgroup analysis by stage.
In this meta-analysis, MSI status does not alter 5-year survival of patients with CRC patients treated with adjuvant 5-FU, however there is significant heterogeneity in the design of individual studies in the data synthesis. More studies are necessary to clarify whether CRC patients with MSI CRC, in particular early stage, should be offered 5-FU based adjuvant chemotherapy.
结直肠癌（CRC）可根据染色体不稳定性途径（微卫星稳定（MSS）途径）和微卫星不稳定性（MSI）途径进行分类。晚期 CRC 手术后的辅助治疗通常基于氟嘧啶 5-氟尿嘧啶（5-FU）单独或与其他药物联合使用。然而，在治疗与 MSI 相关的肿瘤时，5-FU 为基础的方案的使用仍存在争议。
系统研究接受 5-FU 治疗的 CRC 患者肿瘤微卫星图谱与 5 年总生存率之间的关系。
对 PubMed 和 Embase 数据库进行了系统文献回顾。预定义标准确定了研究的纳入/排除标准。分别使用 PRISMA 和 QUADAS-2 标准评估研究的适宜性和质量。患者被分为 MSI 或 MSS CRC。通过 Kaplan-Meier 曲线估计总 5 年生存率。使用漏斗图和 Egger 检验评估发表偏倚。
共确定了 1807 项研究，其中对 9 项研究进行了荟萃分析。与存活者相比，5-FU 治疗后 5 年内死亡的 CRC 患者更有可能患有 MSI，但这并不具有统计学意义。由于数据综合中个别研究的设计存在显著异质性，因此无法进行按阶段进行的亚组分析。
在这项荟萃分析中，MSI 状态并不能改变接受辅助 5-FU 治疗的 CRC 患者的 5 年生存率，但是数据综合中个别研究的设计存在显著异质性。需要更多的研究来阐明是否应该为 MSI CRC 患者，特别是早期阶段的患者，提供基于 5-FU 的辅助化疗。
