Clinical Study On The Effect Of HIVEC With THP On Prevention Of Recurrence And Invasion Of After Surgery Non-Muscular Invasive Bladder Cancer

ObjectiveTo explore the safety and efficacy of the application of the Hyperthermic Intravesical Chemotherapy(HIVEC)with THP on prevention of the recurrence and invasion of Non-Muscular Invasive Bladder Cancer(NMIBC)after Transurethral Resection of Bladder Tumor(TURBt),provide more references for the selection of clinical treatment on NMIBC.Subjects and methodsWe performed a retrospectively analysis on 120 cases of Non-Muscular Invasive Bladder Cancer(NMIBC)who were underwent Transurethral Resection of Bladder Tumor(TURBt)from January 2013 to September 2016 in the First Affiliated Hospital of Zhengzhou University,and the postoperative pathology were confirmed as Urinary transitional cell carcinoma with a pathological stage of non-muscular invasive carcinoma(Ta;Tis;T1).All preoperative examinations of patients showed that there is no obvious abnormality in cardiac and pulmonary function.The routine blood test,liver function,renal function,electrolytes and coagulation function were not significantly abnormal.The preoperative urine was controlled below 5/HP of white blood cells,while other malignant tumors were excluded.The patients after transurethral resection of bladder tumor were divided into two groups by non-randomized concurrent control trial and following the wishes of patients and/or the family members.The group of intravesical chemotherapy with THP was the control group.There were 58 cases,37 male and 21 female,age 34-77 years,the average age is(57.7±9.11)years old in this group.The postoperative pathology according to the 2002 TNM Classification System(UICC)was:Tis 6 cases,Ta 35cases,T1 17 cases.In accordance with WHO 2004 bladder urothelial carcinoma malignant grade grading system,the pathological grade included 33 cases of low-grade urothelial carcinoma and 25 cases of high-grade urothelial carcinoma.According to the number of tumors,there were 13 cases of single tumor,30 cases of2-4 tumors,and 15 cases of more than 4 tumors.All the patients were undergoing the Intravesical Chemotherapy(IVC)with 30mg THP(Pirarubicin)which dissolved in50ml 5%glucose injection after the surgery instantly.The first IVC therapy should be done within 24.0h after the TURBt,and once a week for 6-8 weeks,then changed into once every 4 weeks,lasted 1 year.The group of hyperthermic intravesical chemotherapy with THP was the experimental group.There were 62 cases,40 male and 22 female,age 35-78 years,the average age is(58.4±8.23)years old in this group.The postoperative pathology according to the 2002 TNM Classification System(UICC)was:Tis 5 cases,Ta 38 cases,T1 19 cases.In accordance with WHO 2004bladder urothelial carcinoma malignant grade grading system,the pathological grade included 36 cases of low-grade urothelial carcinoma and 26 cases of high-grade urothelial carcinoma.According to the number of tumors,there were 15 cases of single tumor,31 cases of 2-4 tumors,and 16 cases of more than 4 tumors.All the patients got Hyperthermic Intravesical Chemotherapy(HIVEC)treatment by BR-TRG-Ⅱbody cavity heat perfusion treatment system.All the patients were undergoing the IVC with THP after the TURBt instantly.The IVC therapy which was underwent once a week for 3 weeks.The first HIVEC treatment was in the fourth week after the surgery.Then all patients underwent 1-3 times IVC therapy.The HIVEC treatment should continue 6 times interval every 4 weeks.And then adjusted to once every 3 months when the cystoscopy revealed no recurrence.The total treatment lasted 1 year.The perfusion speed was 100-200 ml/min.The perfusion time was 90.0min.The perfusion entry temperature was(44.0±0.3)℃.The out-body perfusion temperature was(43.0±0.5)℃.The chemotherapeutic drugs of HIVEC was30mg THP same as the IVC therapy,and the solvent was 1500ml 5%glucose injection.All the experimental group patients got the treatment of HIVEC with THP after TURBt.Follow up and observe the patients of the two groups which included in the study by the urinary examination means,such as cystoscopy and color Doppler ultrasound of urinary system.Evaluate the efficacy and safety of the two methods in the clinical treatment of NMIBC by observing and statistically analyzing the post-operative complication rate,tumor progression rate and tumor recurrence rate during the follow-up periods.The criterion of the tumor recurrence was:cystoscopy and pathological examination revealed the recurrence of the tumor in the bladder.The standard of tumor progression was:cystoscopy which was examined every three months showed the recurrence of the bladder tumor,meanwhile the pathological grade of the second surgery were higher than the first operation,or distant metastasis has been found.ResultAll patients were followed up for 12 to 56 months,with a median of 28 months,and there was no patient stopping treatment because of serious complication(such as contraction of the bladder,serious leukopenia,severe anemia,etc.)during the period.The tumor recurrence rate was 22.58%(14/62)in the experimental group and 39.66%(23/58)in the control group.There was a significant difference in the recurrence rate between these two groups(χ~2=4.097,P=0.043<0.05),and the recurrence rate in the control group was significantly higher than that in the experimental group.The tumor progression rate in the experimental group was 9.68%(6/62),and in the control group was 24.14%(14/58).The recurrence rate was significantly different between these two groups(χ~2=4.512,P=0.034<0.05),and the tumor progression rate in the control group was significantly higher than that in the experimental group.According to the distribution of bladder tumor recurrence time,we analyzed the tumor recurrence rate and the median recurrent time by the method of Kaplan-Meier in all of the recurrent patients.The median recurrent time was 13 months in the experimental group and 8months in the control group.The tumor recurrence rate of two groups was statistical significance(log-rank testχ~2=4.622,P=0.032<0.05).The adverse reactions in the two treatments are mainly irritation symptoms of bladder(such as urgency),gross and/or microscopic hematuria,fever,urinary tract infection and so on.No serious complications appeared in this study,such as contraction of the bladder.The irritation symptoms rate was 37.10%(23/62)in the experimental group and 36.21%(21/58)in the control group.The gross hematuria rate was 22.58%(14/62)in the experimental group and 20.69%(12/58)in the control group.The urinary tract infection rate was16.13%(10/62)in the experimental group and 13.79%(8/58)in the control group.The fever rate was 9.78%(6/62)in the experimental group and 10.34%(6/58)in the control group.There was no significant difference in the incidence of the all adverse reactions between the two groups.(P>0.05).Conclusion1.The effect of TURBt combined with THP HIVEC is obvious better than TURBt combined with normal temperature THP IVC on prevention of recurrence and progression of NMIBC.2.The post-operative complication in the group of TURBt combined with normal temperature THP IVC has no obvious increase,compared to the group of TURBt combined with THP HIVEC.It demonstrates that the method of HIVEC is safe and reliable.