Comparison Of Efficacy And Safety Of Total Cystectomy And Bladder Preservation In The Treatment Of Muscular Invasive Bladder Cancer

Objective1.To compare the curative effect of TURBT combined with chemotherapy and adjuvant chemotherapy after radical cystectomy in patients with muscle-invasive bladder cancer,to explore the feasibility and superiority of bladder preservation therapy,to find out the best bladder preservation treatment conditions,and to provide clinical basis for patients to choose different treatment schemes.2.To explore the feasibility and safety of PD-1 inhibitor in bladder preservation therapy for muscle-invasive bladder cancer,to compare the efficacy and safety of radical cystectomy combined with chemotherapy,TURBT combined with chemotherapy,and postoperative adjuvant chemotherapy combined with PD-1 inhibitor after TURBT.Methods1.The patients with muscle-invasive bladder cancer treated in the department of urology in Xijing Hospital from January 2015 to December 2019 were collected retrospectively.the baseline data and perioperative indexes of the patients were collected,and the patients were followed up.The contents of the follow-up included the patient’s survival,tumor recurrence,adverse reactions and so on.Kaplan-Meier method was used to draw survival curve,and Cox regression was used for univariate and multivariate analysis to explore the relationship between clinical features and OS and DFS.2.Patients with muscle-invasive bladder cancer treated in the department of urology in Xijing Hospital from January 2020 to December 2021 were collected retrospectively,and their baseline data,follow-up information and adverse reactions were collected.The survival curve was drawn by Kaplan-Meier method,and univariate and multivariate analysis was conducted with Cox regression model to explore the relationship between clinical features and DFS,as well as the correlation between PD-L1 expression and DFS and adverse reactions.Results1.Total cystectomy group（n=78）and bladder preservation group（n=31）.Compared with the perioperative data,the operation time,the intraoperative blood loss and hospitalization days were 356.92（±66.82）min;361.54（±109.32）ml;17.17（±8.06d）days.The bladder-conserving group was 51.29（±10.88）min;52.74（±26.29）ml;7.58（±2.14）days,the difference was statistically significant（P<0.05）.The early postoperative complications included radical operation group（n=70）and bladder preservation group（n=10）.Among them,there were more patients with fever in the total cystectomy group and no fever in the bladder preservation group,and the difference was statistically significant（P<0.05）.Up to the end of observation,the two groups did not reach the median OS due to the limited follow-up time,P=0.4558,there was no significant difference in OS between the two groups Cox regression analysis showed that the number of tumors（HR:5.662,95%CI:1.257～25.751,P=0.036）;Clinical stage T₄（HR:2.618,95%CI:1.134～8.437,P=0.039）;histology and pathology（HR:1.786,95%CI:1.186～2.6,P=0.006）were independent risk factors for OS.The m DFS of total cystectomy group was 48.2 months（95%CI:29.9～66.5 months）,and the m DFS of bladder preservation group was 32.7months（95%CI:23.8～41.5 months）,The difference of m DFS between the two groups was statistically significant（P=0.044）.The Cox regression analysis showed that the number of tumors（HR:2.164,95%CI:1.263～3.629,P=0.013）and Clinical stage T₄（HR:1.293,95%CI:1.032～4.785,P=0.039）were are independent risk factors for DFS.2.Total cystectomy group（n=27）,double bladder preservation group（n=15）and triple bladder preservation group（n=23）.At the end of follow-up,there were 4 cases of recurrence in the total cystectomy group,4 cases in the duplex group and 2 cases in the triad group.The three groups did not reach the median DFS,because the follow-up time was too short.In stratified comparison,the total cystectomy group and the combined bladder preservation group were 0.0472,the total cystectomy group and the triple bladder protection group were 0.9749,the two combined bladder preservation group and the triple bladder preservation group were 0.0237.Cox regression analysis showed that choose the scheme of dual bladder protection（HR:2.264,95%CI:1.083～7.695,P=0.037）and clinical stage T₄（HR:2.839,95%CI:1.139～6.936,P=0.024）were independent risk factors for DFS.A total of 65 adverse events occurred in the total cystectomy group,including 9 cases of grade 3-4adverse events,43 cases of grade 3-4 adverse events in the combined bladder preservation group,3 cases of grade 3-4 adverse events and 46 cases of grade 3-4 adverse events in the triple bladder preservation group.there were 5 cases of grade 3-4 adverse reactions.A total of 15 immune-related adverse events occurred in the triple bladder protection group,all of which were grade 1-2 adverse events.In the triple bladder preservation group,there were14 PD-L1 positive patients and 9 PD-L1 negative patients,of which 2 patients relapsed in the PD-L1 negative group,while none of the PD-L1 positive patients relapsed.,P=0.201,PD-L1 negative and PD-L1 positive were not related to DFS.In the triple bladder protection group,there were 11 adverse events in PD-L1 positive patients and 4 adverse events in PD-L1 negative patients,P>0.05.There was no significant difference between them.Conclusions1.Compared with the total cystectomy group,the OS of the patients who received adjuvant chemotherapy after TURBT was not significantly different from that of the total cystectomy group,but the DFS was significantly lower than that of the cystectomy group.A number of perioperative treatment indexes in the bladder preservation group were significantly better than those in the total cystectomy group.In addition,multivariate analysis showed that tumor number,clinical stage T₄ and histology were independent risk factors for OS,while tumor number and clinical stage T₄ were independent risk factors for DFS,which provided an important basis for patients’choice of treatment.2.From the DFS point of view,TURBT postoperative adjuvant chemotherapy combined with PD-1 inhibitor triple bladder preservation group and total cystectomy group are significantly better than the dual bladder preservation group,but the difference between the former two is not significant,there is no statistical significance.The triple bladder protection scheme combined with PD-1 inhibitor can make up for the poor DFS of the bladder protection scheme,and it is a major optimization of the bladder protection scheme.There was no significant increase in adverse reactions in the triple bladder protection group,and there were fewer serious immune adverse events.Multivariate analysis showed that the choice of bladder protection regimen and clinical stage T₄ were independent risk factors for DFS.In addition,there was no significant correlation between the expression of PD-L1 and DFS and immune adverse events.Overall,the combination of PD-1 inhibitor is effective and safe,which is worthy of further exploration and verification in the next prospective randomized controlled study.