Li Shuofeng, Wei Ran, Yu Guanhua, Liu Hengchang, Chen Tianli, Guan Xu, Wang Xishan, Jiang Zheng
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2022 Aug 24;12:982792. doi: 10.3389/fonc.2022.982792. eCollection 2022.
Radiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).
The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan-Meier analysis.
A total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT-BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P<0.001; NRT vs. EBRT-BRT, adjusted HR= 2.16, 95% CI: 1.78-2.63, P<0.001). The results of the dynamic SIR and Poisson regression analysis for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency and was significantly related to the variations of age at PC diagnosis and decreased with time progress. For OS, the SBC after NRT, SBC after EBRT, and SBC after EBRT-BRT of 10-year survival rates were 37.9%, 29.2%, and 22.2%, respectively.
Radiotherapy for primary PC was associated with higher risks of developing SBC than patients unexposed to radiotherapy. Different pelvic RT treatment modalities had different effects on the risk of SBC.
放射治疗（RT）是盆腔癌（PC）局部控制的关键手段，但盆腔放疗对继发性恶性肿瘤发生的影响仍不明确。本研究旨在确定原发性PC放疗与后续继发性膀胱癌（SBC）之间的关系。
查询监测、流行病学和最终结果（SEER）数据库（1975年至2015年）中的PC病例。采用Fine-Gray竞争风险回归和Cox回归分析评估SBC的累积发病率。使用泊松回归和多重原发性标准化发病比（SIR）评估接受放疗患者的放疗相关风险。还对根据PC诊断后的潜伏时间、PC诊断年份阶段和PC诊断时年龄分层的患者进行了亚组分析。通过Kaplan-Meier分析比较不同SBC治疗组的总生存期（OS）。
总共318,165例观察结果显示，原发性癌症位于盆腔，256,313例患者未接受放疗（NRT），51,347例患者接受了外照射放疗（EBRT），10,505例接受EBRT和近距离放疗联合治疗（EBRT-BRT）的患者发生了SBC。在Fine-Gray竞争风险回归中，接受两种放疗与PC患者发生SBC的较高风险密切相关（NRT与EBRT相比，调整后HR = 1.71，95%CI：1.54 - 1.90，P < 0.001；NRT与EBRT-BRT相比，调整后HR = 2.16，95%CI：1.78 - 2.63，P < 0.001）。SBC的动态SIR和泊松回归分析结果显示，放疗后早期潜伏时SBC风险略有增加，且与PC诊断时年龄的变化显著相关，并随时间推移而降低。对于OS，NRT后发生SBC、EBRT后发生SBC和EBRT-BRT后发生SBC的10年生存率分别为37.9%、29.2%和22.2%。
与未接受放疗的患者相比，原发性PC放疗与发生SBC的较高风险相关。不同的盆腔RT治疗方式对SBC风险有不同影响。
