Efficacy Analysis Of A Novel Intravesical Thermochemotherapy Scheme For Preventing The Recurrence Of Intermediate- And High-risk Nonmuscle-invasive Bladder Cancer

BackgroundIn 2019,the American Cancer Society counted 1762450 new cancers in the United States,including 158220 new cancers of the urinary system and 80470 bladder cancers.Bladder cancer is one of the top 10 tumors with the highest incidence among men in the world intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC)accounts for about 75%of bladder cancer.Up to 70%of bladder cancer relapses within one year,and up to 20%of patients progress to muscle invasive bladder cancer(MIBC)two years.The standard treatment for intermediate-and high-risk NMIBC,is transurethral resection of bladder tumor(TURBT),followed by intravesical adjuvant therapy.However,the best strategy of intravesical adjuvant therapy to prevent tumor recurrence after TURBT has not been clarified So far,intravesical adjuvant therapy has mainly focused on immunotherapy,mainly Bacillus Calmette Guerin(BCG),chemotherapy and cytotoxic drugs combined with hyperthermia BCG,is recommended for high-risk NMIBC,worldwide.However,due to the worldwide shortage of BCG,the high incidence of local toxicity and the high price of BCG,many patients give up using BCG.The same is true in China,where the main choice of bladder cancer patients is intravesical adjuvant chemotherapy.Hyperthermia itself plays an anti tumor effect through a variety of mechanisms,and the addition of chemotherapy makes it play an effect 1+1>2ObjectiveTo compare the efficacy and safety of a novel thermochemotherapy scheme and the instillation of chemotherapy agents without hyperthermia in patients with intermediate-and high-risk NMIBCMaterials and methodsBetween June 2012 to February 2018,450 patients with urothelial cancer who undergoing intravesical adjuvant therapy with pirarubicin and gemcitabine after TURBT were enrolled in the study.The patients were divided into two groups:intravesical instillation chemotherapy without hyperthermia group and intravesical thermochemotherapy group.In the intravesical instillation chemotherapy without hyperthermia group,intravesical instillation was performed at room temperature,once a week for 8 times,and then once a month for 10 times.In the intravesical thermochemotherapy group,intravesical instillation was performed 8 times a week,followed by 10 times a month.The first instillation was composed of three consecutive sessions(perioperative high-frequency thermochemotherapy)which only the second hyperthermia combined with pirarubicin or gemcitabine,but the first and the third hyperthermia did not combine with pirarubicin or gemcitabine.Perioperative high-frequency thermochemotherapy followed by intravesical instillation with pirarubicin or gemcitabine without using hyperthermia).The patients were reexamined by urine cytology and cystoscopy every 3 months for 24 months,and then every 6 months.The primary end point was 24-month recurrence-free survival(RFS).Secondary endpoints included 24-month progression-free survival(PFS)and adverse events.The continuous variables were compared by Mann-Whitney U test or Wilcoxon rank sum test,and the classified variables were compared by Pearson chi-square test or Yates correction chi-square test The 24-month RFS and 24-month PFS after TURBT were evaluated by Kaplan-Meier method and log-rank test.In order to determine the independent predictors of recurrence after TURBT,Cox proportional hazard model was used for univariate regression analysis and multivariate regression analysisResults124 patients in the thermochemotherapy group and 120 patients in the intravesical instillation chemotherapy without hyperthermia group were enrolled in this study,and the baseline characteristics of the two groups were well balanced.The 24-month RFS of the thermochemotherapy group and the intravesical instillation chemotherapy without hyperthermia group were 82.3%and 66.7%respectively(log-rank p=0.0051).The PFS of patients in the thermochemotherapy group was significantly higher than that in the b intravesical instillation chemotherapy without hyperthermia group(95.2%vs.86.7%,log rank p=0.015).According to the Cox proportional hazard model,the independent factors for improving efficacy were the use of thermochemotherapy with pirarubicin(hazard ratio,0.445;95%confidence interval,0.237-0.836;p=0.012)and thermochemotherapy with(hazard ratio,0.405;95%confidence interval,0.173-0.948;p=0.037).The instillation-related adverse events in both groups were grade 1 to grade 2.The overall adverse events in the thermochemotherapy group(49/124)were higher than those in the intravesical instillation chemotherapy without hyperthermia group(40/120),but there was no significant difference between the two groups(?2=0.469,p=0.493).ConclusionThe perioperative high-frequency thermochemotherapy scheme is a safe and effective adjuvant treatment option after TURBT for patients with intermediate-and high-risk NMIBC.