Ruan Yibing, Carbonell Chantelle, Brown Karen, Hilsden Robert J, Brenner Darren R
Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada.
Cancer Control. 2025 Jan-Dec;32:10732748251344481. doi: 10.1177/10732748251344481. Epub 2025 May 20.
BackgroundColorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide. Colorectal adenomas (CRAs) are a crucial precursor for CRC and a target for preventive strategies. Recent network meta-analyses (NMAs) of randomized controlled trials (RCTs) suggest that chemopreventive agents (CPAs) are associated with reductions in CRC incidence. However, the quality of this evidence is low due to significant variability in the methods and types of studies assessed.PurposeOur study reviewed the efficacy and safety of CPAs on CRAs or CRCs evaluated in NMAs of RCTs and assessed the quality of all published NMAs on CPAs.Research DesignWe searched PubMed, Embase, and Cochrane Library for studies published from inception to July 29, 2024. We included all NMAs assessing the efficacy and safety of CPAs on CRC in both average-risk (general population) and high-risk (previous history of adenoma/CRC) populations. ResultsNine NMAs comparing 15 different interventions were included. Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib were the most studied. Aspirin demonstrated efficacy against the development of any CRA and low-dose aspirin was consistently more protective than high-dose aspirin. However, the effect of aspirin against advanced CRA was not statistically significant. Concerns for long-term aspirin use included an increased risk of gastrointestinal bleeding and ulceration, but when evaluating all serious adverse events (SAEs), aspirin users did not have an increased risk compared to controls. Non-aspirin NSAIDs showed better efficacy against advanced CRA. However, the use of non-aspirin NSAIDs such as celecoxib was associated with significantly increased risk of SAEs, particularly cardiovascular disease events.ConclusionsConsidering the balance of efficacy and safety, low-dose aspirin is currently the best option for chemoprevention of CRA/CRC. Future research is needed to better characterize the patient subgroups that benefit most and to develop new, more effective CPAs.
背景
结直肠癌（CRC）是全球第三大最常被诊断出的癌症，也是癌症相关死亡的第二大主要原因。结直肠腺瘤（CRAs）是CRC的关键前体，也是预防策略的目标。近期对随机对照试验（RCTs）的网络荟萃分析（NMAs）表明，化学预防剂（CPAs）与CRC发病率的降低有关。然而，由于所评估研究的方法和类型存在显著差异，该证据的质量较低。
目的
我们的研究回顾了在RCTs的NMAs中评估的CPAs对CRAs或CRCs的疗效和安全性，并评估了所有已发表的关于CPAs的NMAs的质量。
研究设计
我们在PubMed、Embase和Cochrane图书馆中搜索了从创刊到2024年7月29日发表的研究。我们纳入了所有评估CPAs在平均风险（一般人群）和高风险（既往腺瘤/CRC病史）人群中对CRC的疗效和安全性的NMAs。
结果
纳入了比较15种不同干预措施的9项NMAs。阿司匹林和非阿司匹林非甾体抗炎药（NSAIDs）如塞来昔布是研究最多的。阿司匹林对任何CRA的发生都有疗效，低剂量阿司匹林始终比高剂量阿司匹林更具保护作用。然而，阿司匹林对晚期CRA的作用在统计学上并不显著。长期使用阿司匹林的担忧包括胃肠道出血和溃疡风险增加，但在评估所有严重不良事件（SAEs）时，与对照组相比，阿司匹林使用者的风险并未增加。非阿司匹林NSAIDs对晚期CRA显示出更好的疗效。然而，使用塞来昔布等非阿司匹林NSAIDs与SAEs风险显著增加有关，尤其是心血管疾病事件。
结论
考虑到疗效和安全性的平衡，低剂量阿司匹林目前是化学预防CRA/CRC的最佳选择。未来需要开展研究，以更好地确定最能获益的患者亚组，并开发新的、更有效的CPAs。
