| Objectiv:Bladder cancer is the second most common malignancy of the genitourinary system after prostate cancer.About 75%of patients with newly diagnosed bladder cancer are non-muscle-invasive bladder cancer.The guidelines recommend intravesical chemotherapy or immunotherapy for NMIBC patients undergoing Transurethral resection of bladder tumor.At present,BCG is the standard treatment for intermediate-risk and high-risk patients,but there are still some patients with recurrence or progression to higher-grade tumors.Some studies have shown that BCG combined with MMC has higher anti-tumor activity,and many researchers have also explored the efficacy of the combination,but the conclusions are not the same.Therefore,the purpose of this Meta-analysis was to evaluate the efficacy and safety of BCG combined with MMC compared with intravesical instillation of BCG alone in patients with NMIBC.Method:A systematic literature search was conducted on the databases of PubMed,EMBASE,CochraneLibrary,CNKI,CBM,VIP,Wanfang,etc.,to find the related randomized controlled trials(RCTs)of patients with NMIBC treated by intravesical instillation of BCG combined with MMC and BCG alone.The search time was up to December 31,2020.The search results were independently screened by two researchers according to the inclusion and exclusion criteria,and finally the data were analyzed by RevMan5.4 software and Stata16.0.Results:Eleven RCTs were included in this meta-analysis,with a total of 1349 subjects.The results showed that compared with BCG alone,BCG combined with MMC had lower disease recurrence rate(RR=0.66,95%CI 0.56-0.77,P<0.01),disease progression rate(RR=0.61,95%CI 0.44-0.84,P=0.003)and disease-specific mortality(RR=0.46,95%CI 0.26-0.78,P=0.004).However,there was a higher incidence of systemic adverse reactions(RR=1.57,95%CI 1.22-2.02,P=0.0004).There was no significant difference in the incidence of local adverse reactions and all-cause mortality between the two groups.The results of subgroup analysis showed that for patients with Tis,there was no significant difference in disease recurrence rate between the two groups(RR=0.77,95%CI 0.58-1.03,P=0.08).There was no significant difference in disease recurrence between the two groups when induction intravesical was used(RR=0.81,95%CI 0.37-1.77,P=0.59).In addition,the combination group had a lower disease recurrence rate regardless of sequential or alternate infusion and regardless of BCG dose of 80mg or 120mg(P<0.05).Conclusion:Compared with BCG intravesical alone,the combined group showed better efficacy for Ta and T1 stage patients,while there was no significant difference for Tis stage patients.In addition,the combination was associated with a higher incidence of adverse events,while there was no significant difference in the incidence of local adverse events and all-cause mortality between the two groups.There was no significant difference in disease recurrence between the two groups when induction intravesical was used,but the combination group had a lower rate of disease recurrence regardless of sequential or alternate perfusion and whether BCG was administered at 80mg or 120mg.Due to the limitation of the number of included studies,the dose of the intervention,BCG strain and the risk stratification of NMIBC patients and other factors,multi-center,high-quality studies with more rigorous experimental design are needed to further explore the efficacy and safety of the two-drug combination perfusion in the future. |
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