前列腺癌患者经放射治疗后发生第二原发膀胱癌的风险分析

Risk analysis of second primary bladder cancer after radiotherapy in patients undergoing radical prostatectomy

目的探究经放射治疗后前列腺癌患者发生第二原发膀胱癌(SPBC)的风险并评估结果对未测得混杂的稳健性。方法选取美国“监测、流行病学和结果(SEER)”数据库中2004年至2009年病理诊断明确的前列腺癌患者资料,根据是否接受放射治疗分为放疗组和未放疗组,应用倾向性评分匹配(PSM)对两组患者进行匹配;使用竞争风险模型评估放疗后前列腺癌患者SPBC的发生风险,并采用未测得混杂敏感性分析,评估结果和结论的稳健性。结果本研究共纳入83064名前列腺癌根治术患者,其中接受放疗的为5141例(88例发生SPBC),未接受放疗的为77923例(753例发生SPBC)。匹配前后竞争风险模型显示,放疗增加前列腺癌患者发生SPBC的风险(匹配前SHR为1.438,95%置信区间1.133~1.824,P=0.003;匹配后SHR为1.586,95%置信区间1.076~2.215,P=0.007)。敏感性分析结果显示,未测得混杂与放疗和SPBC发生的关联为OR=1.65,SHR=1.84可以使观察到的放疗-SPBC发生风险关联无统计学意义。结论对放疗导致前列腺癌患者SPBC发生风险增高应谨慎判断,某个与结局或放疗关联较低的混杂因素就可能将结果推至无效。

Objective To investigate the risk of second primary bladder cancer(SPBC)in prostate cancer patients after radiation therapy and to assess the robustness of the results to unmeasured confounding.Methods Data from the surveillance,epidemiology and end results(SEER)database of prostate cancer patients with a clear pathological diagnosis from 2004 to 2009 were selected.Patients were divided into radiotherapy and non-radiotherapy groups according to whether they received radiotherapy or not.PSM was applied to match the two groups of patients,the risk of SPBC in post-radiation prostate cancer patients was evaluated using a competing risk model,and sensitivity analysis for unobserved confounders was performed to assess the robustness of results.Results Totally 83064 radical prostatectomy patients were included in this study,of whom 5141(88 with SPBC)and 77923(753 with SPBC)were categorized into radiotherapy and non-radiotherapy group.Pre-and post-matching competing risk models showed that radiotherapy increased the risk of SPBC in patients undergoing radical prostatectomy(pre-matching SHR=1.438,95%CI=1.133-1.824,P=0.003;post-matching SHR=1.586,95%CI=1.076-2.215,P=0.007).Sensitivity analysis showed that the association of unmeasured confounding with radiotherapy and SPBC OR=1.65,and SHR=1.84 could make the observed difference in SPBC between radiotherapy and non-radiotherapy patients insignificant.Conclusion The increased risk of SPBC in prostate cancer patients due to radiotherapy should be judged with caution,and a confounding factor with a relatively low association with outcome or treatment may nullify the results.