Background Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users. Methods Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004–12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients. Results Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up. Conclusions Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.

中文翻译：

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使用模拟试验来研究使用氮基双膦酸盐与上皮性卵巢癌风险之间的关联


背景 上皮性卵巢癌 (EOC) 是女性第八大常见癌症，生存结果较差。观察证据表明，氮基双膦酸盐 (NBB) 的使用可能与 EOC 风险降低相关，特别是子宫内膜样组织型和浆液性组织型；然而，指示混淆是一个问题。研究 NBB 化学预防潜力的另一种方法是通过识别所有开始使用 NBB 的女性来模拟目标试验，并调查继续使用 NBB 的女性与停止使用 NBB 的女性发生 EOC 的风险。方法 使用基于人群的关联数据，我们确定了所有在 2004-12 年首次使用 NBB 的 50 岁以上澳大利亚女性。我们使用首次使用后的年份来定义每位女性的治疗是继续使用还是停止使用。我们使用稳定的逆概率权重来模拟随机化，以使用年龄、合并症和社会经济地位等协变量来平衡治疗组。我们从治疗分配开始对女性进行跟踪，直至 EOC 诊断、死亡或 2013 年 12 月 31 日。我们使用灵活的参数事件时间模型评估了 EOC 的风险（总体风险和组织型风险），考虑到随时间变化的影响，并产生了随时间变化的系数。结果 在研究中的 313 383 名女性中，472 名在随访期间被诊断为 EOC（261 名浆液性 EOC），诊断时的平均年龄为 72 岁。与停止治疗相比，继续使用 NBB 与总体 EOC（HR = 0.87，95% CI：0.69，1.10）和浆液性 EOC（HR = 0.71，95% CI：0.53，0.96）风险降低相关。在9年的随访中保持稳定。 结论 我们的模拟试验结果表明，与停止使用的女性相比，开始 NBB 治疗的女性中，继续使用的女性被诊断为整体 EOC 和浆液性 EOC 的风险分别降低了 13% 和 29%。