Haug Ala Jabri, Støer Nathalie, Langseth Hilde, Siafarikas Franziska, Botteri Edoardo, Fortner Renée Turzanski, Lindemann Kristina
Akershus University Hospital, Lørenskog, Norway.
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Int J Cancer. 2025 Jul 15;157(2):277-287. doi: 10.1002/ijc.35363. Epub 2025 Feb 24.
While nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to improve survival in certain cancers, data in patients with endometrial cancer (EC) is conflicting. This study investigated use of aspirin and nonaspirin NSAIDs (NA-NSAIDs) and EC-specific-and all-cause death. This nationwide cohort study linked data from the Cancer Registry of Norway with The Norwegian Prescription database. Patients diagnosed with EC from 2004 to 2018 were included. Post-diagnosis exposure to aspirin and NA-NSAIDs was defined as ≥3 consecutive prescriptions ≥30 days after EC diagnosis, with pre-diagnosis use as ≥2 filled prescriptions <6 months prior to diagnosis. Follow-up started 10 months after diagnosis. Hazard ratios for the risk of death were calculated with multivariable Cox-regression models. Our study population included 7751 individuals with EC, 685 (9%) were aspirin users and 620 (8%) were NA-NSAIDs users. The median follow-up time was 5.0 years, with 1518 (20%) deaths observed (n = 728 (9%) EC-specific). In multivariable analysis, aspirin use was significantly associated with a 19% higher risk of all-cause death compared to non-users (HR = 1.19, 95% CI [1.01-1.41]). The association was stronger among combined pre- and postdiagnosis use (HR = 1.35 [1.12-1.64]). NA-NSAIDs use increased risk of cancer-related death (HR = 1.25 [0.99-1.58]) and there was a dose-response association with significantly higher risk of cancer-specific death with higher cumulative doses (HR = 1.33 [1.02-1.75]). We found a higher risk of cancer-specific-and all-cause death among patients that used aspirin and NA-NSAIDs after a diagnosis of EC. Further studies on the biological mechanisms underlying these associations are needed.
虽然非甾体抗炎药（NSAIDs）已被证明可提高某些癌症患者的生存率，但子宫内膜癌（EC）患者的数据却相互矛盾。本研究调查了阿司匹林和非阿司匹林类NSAIDs（NA-NSAIDs）的使用情况以及EC特异性死亡和全因死亡情况。这项全国性队列研究将挪威癌症登记处的数据与挪威处方数据库相链接。纳入了2004年至2018年诊断为EC的患者。诊断后使用阿司匹林和NA-NSAIDs的定义为EC诊断后≥30天连续≥3次处方，诊断前使用定义为诊断前<6个月≥2次已配药处方。随访从诊断后10个月开始。使用多变量Cox回归模型计算死亡风险的风险比。我们的研究人群包括7751例EC患者，其中685例（9%）为阿司匹林使用者，620例（8%）为NA-NSAIDs使用者。中位随访时间为5.0年，观察到1518例（20%）死亡（n = 728例（9%）为EC特异性死亡）。在多变量分析中，与未使用者相比，使用阿司匹林与全因死亡风险显著高19%相关（HR = 1.19，95%CI[1.01 - 1.41]）。诊断前和诊断后联合使用时这种关联更强（HR = 1.35[1.12 - 1.64]）。使用NA-NSAIDs会增加癌症相关死亡风险（HR = 1.25[0.99 - 1.58]），并且存在剂量反应关联，累积剂量越高，癌症特异性死亡风险显著越高（HR = 1.33[1.02 - 1.75]）。我们发现，EC诊断后使用阿司匹林和NA-NSAIDs的患者中，癌症特异性死亡和全因死亡风险更高。需要对这些关联背后的生物学机制进行进一步研究。
