膀胱癌术后放疗与第二原发直肠恶性肿瘤的关联性研究:一项基于大队列的回顾性研究

Association between postoperative radiotherapy for bladder cancer and second primary rectal cancers:a retrospective cohort study

目的探讨膀胱癌术后放疗与发生第二原发肿瘤直肠癌风险的关系。方法从美国国立癌症研究所肿瘤监测、流行病学和结果数据库(SEER)(1975—2017)中纳入符合标准的膀胱癌患者75120例。第二原发肿瘤定义为膀胱癌治疗后5年以上发生的直肠癌,第二原发肿瘤直肠癌的累积发病率通过Fine⁃Gray竞争风险回归进行估计。用泊松回归评估放疗患者与未放疗患者中直肠癌的相对风险。结果在75120例患者中,70045例(92.4%)为白人,中位年龄65.8岁(54~74岁)。2236例(3%)接受了术后放疗,72884例(97%)仅接受了手术治疗。在放疗和非放疗患者中,30年随访期间直肠癌的累积发生率分别为0.93%和0.43%(P=0.004)。在竞争风险回归分析中,接受放疗与发生直肠癌明显相关(HR=1.86;95%CI 1.26~2.74,P=0.009)。直肠癌放疗相对风险(RR)随着直肠癌诊断时间越早增加越显著(1975—1985 v.s.1985—1994:RR=2.59;95%CI 1.20~4.86,P<0.001),放疗时年龄越小发生第二原发肿瘤的概率越大(≤50岁vs.>50岁:RR=7.89;95%CI 2.97~21.30,P<0.001);使用泊松分布计算放疗患者直肠第二肿瘤相对风险均更高(RR=2.20;95%CI 1.45~3.18,P<0.001),诊断日期调整后,放疗患者直肠第二肿瘤风险仍更高(RR=1.77;95%CI 1.17~2.57,P=0.009)。结论膀胱癌放疗后发生直肠癌的风险增加,应积极随诊检查尽早发现膀胱癌放疗后相关的第二原发肿瘤直肠癌。

Objective To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods Eligible 75120 patients with bladder cancer from the Surveillance,Epidemiology,and End Result database(SEER)of the National Cancer Institute(NCI)(1975-2017)were enrolled in this study.The second primary cancers referred to rectal cancers patients suffered after more than five years post⁃treatment for bladder cancer,and the cumulative incidence was estimated using Fine⁃Gray competing risk regression.The relative risk(RR)of rectal cancer in patients treated with or without radiotherapy(the RT group or the NRT group)was evaluated using Poisson regression.Results Among the 75120 patients,70045(92.4%)were Caucasian,with a median age of 65.8 years(54-74 years).A total of 2236(3%)received postoperative radiotherapy,while 72884(97%)received surgery alone.The 30⁃year follow⁃up revealed a cumulative incidence of rectal cancer of 0.93%in the RT group and 0.43%in the NRT group(P=0.004).The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer(HR:1.86;95%CI 1.26-2.74,P<0.009).Furthermore,the RR of radiotherapy⁃associated rectal cancer significantly increased as the diagnosis occurred earlier(1975-1985 vs.1985-1994:RR 2.59;95%CI 1.20-4.86,P<0.001),and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors(≤50⁃year old vs.>50 year old:RR 7.89,95%CI 2.97-21.30,P<0.001).As calculated using the Poisson distribution,the RR of second rectal tumors was higher in the RT group(RR:2.20,95%CI 1.45-3.18,P<0.001),even after adjusting the date of diagnosis(RR:1.77,95%CI 1.17-2.57,P=0.009).Conclusions An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow⁃ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.