Radiotherapy For Non-metastatic Prostate Cancer Increases The Risk Of Second Malignancies In The Pelvic Region:an Analysis Based On SEER Database

Purpose:The aim of our study is to compare the occurrence of secondary pelvic malignancies(SPMs),including bladder and rectal cancers,between prostate cancer(PCa)patients treated with surgery and those treated with radiotherapy(RT),based on large population and long-term follow-up data.This will help verify whether RT increases the risk of SPMs in PCa patients.The results can guide clinical treatment decisions for PCa patients and provide reference for post-radiation therapy follow-up.Methods:This study was a retrospective cohort study based on the Surveillance,Epidemiology,and End Results(SEER)program of the US National Cancer Institute.Patients with primary PCa as the first cancer diagnosis were selected from the SEER database(1975-2018).PCa patients were divided into RT group and surgery group based on the treatment modality received.The cumulative incidence rates of SPMs were calculated using Fine-Gray competing risk regression analysis for the RT and surgery groups separately.Follow-up completion or death due to any cause was considered as a competing event for the occurrence of SPMs.Univariate competing risk regression analysis was used to screen for factors related to the occurrence of pelvic malignant tumors,and variables with statistical significance were included in multivariate competing risk regression analysis.Poisson regression analysis was used to calculate the standardized incidence rates(SIR)to compare the incidence rates of bladder and rectal cancer between prostate cancer patients and the general population.Results:1.We included 390,393 PCa patients who met the inclusion criteria,of whom146,856(37.61%)received RT and 243,537(62.39%)received surgery for PCa.2.PCa patients who received RT had a significantly higher incidence of bladder cancer(BC)(SIR=1.47,95%CI=1.42-1.52)and rectal cancer(RC)(SIR=1.55,95%CI=1.44-1.67)than the general population.In the surgery group,we did not observe a higher incidence of BC and RC than the general population(BC: SIR=0.82,95%CI=0.8-0.85;RC: SIR=0.81,95%CI=0.75-0.87).3.When we performed subgroup analysis based on patient age and survival time,the SIR for BC and RC remained higher in the RT group than the general population,while the SIR in the surgery group remained unchanged compared to the general population.4.The cumulative incidence of BC and RC was significantly higher in the radiation therapy group than in the surgery group.Subgroup analysis based on patient age and diagnosis year did not substantially alter the results.5.In univariate competing risk regression analysis,diagnosis of year,treatment,and survival time were associated with the occurrence of SPMs in PCa patients.In the multivariable analysis,only treatment and survival time were significantly associated with the occurrence of SPMs,with patients in the RT group having a significantly higher risk of BC or RC than those in the surgery group(HR=1.87,95%CI=1.26-2.7,P<0.001).Conclusion:1.This study found that patients with non-metastatic prostate cancer who received radiation therapy had a significantly increased risk of developing secondary bladder or rectal cancer compared to those who received surgical treatment after 5years of treatment.2.This risk became more significant as the survival time was prolonged,and in the latest data(2004-2013),this risk still existed.3.This study also observed that the incidence of bladder and rectal cancer in patients with prostate cancer who received radiation therapy was higher than that of the general population.However,this result was not observed in patients who received surgical treatment.4.The increased risk of bladder or rectal cancer in patients with prostate cancer who received radiation therapy might have an impact on public health,cancer monitoring,and patient treatment selection.Meanwhile,the monitoring of bladder and rectal cancer in patients with PCa who received radiation therapy required more attention in the future.Perhaps most importantly,this study confirmed the belief that secondary malignancies should be added to the avoidable risk list associated with radiation therapy for low-risk PCa patients who do not need treatment.