The Efficacy Of Combined Androgen Blockade And Castration Alone In The Treatment Of Advanced Prostate Cancer:A Meta-analysis

Objective:To systematically evaluate the efficacy of combined androgen blockade in the treatment of advanced prostate cancer,and to compare the efficacy of new combined androgen blockade(abiraterone acetate combined with castration)with traditional combined androgen blockade(nonsteroidal anti-androgens combined with castration).Methods:PubMed,Cochrane Library,EMBASE,Web of science,CNKI,Wanfang,VIP,CBM and other databases were searched by computer from inception to July,2019;at the same time,the ongoing trials were supplemented and searched,including the Chinese clinical trial registration platform and the US clinical trials(Clinical Trials);in addition,manual search was carried out Search for"Chinese Journal of Urology","Chinese Journal of Andrology","Journal of clinical urology","Journal of modern urology"and other professional journals from 1985 to 2019.We collected randomized controlled trial(RCT)literatures published at home and abroad on combined androgen blockade and castration alone in the treatment of advanced prostate cancer.Two researchers independently conducted literature search and screening,data extraction,data transformation and quality evaluation,and cross checked the results.When there is a dispute on the results,it should be solved through discussion or by the third researcher through consultation.Revman 5.3and stata15 software were used for meta analysis,and indirect comparison was made by using the indirect package of Stata.Results:A total of 14 RCT were included in this study,including 8050 patients.Meta analysis showed that:compared with castration alone,combined androgen blockade could significantly improve the overall survival(HR=0.79,95%CI 0.75 to 0.85,P<0.00001),progression free survival(HR=0.68,95%CI 0.55 to 0.84,P=0.0004)and tumor response rate(RR=1.35,95%CI 1.11 to 1.64,P=0.003).The results of overall survival subgroup analysis showed that traditional combined androgen blockade(HR=0.85,95%CI 0.79 to0.91,P<0.00001)and new combined androgen blockade(HR=0.65,95%CI 0.57 to 0.73,P<0.00001)could significantly improve the overall survival of prostate cancer patients and there was a difference between the two groups(I~2=92.8%,P=0.0002);the results of progression free survival subgroup analysis showed that traditional combined androgen blockade(HR=0.79,95%CI 0.72 to 0.86,P<0.00001)and new combined androgen blockade(HR=0.42,95%CI 0.37 to 0.48,P<0.00001)could significantly improve the progression free survival of prostate cancer patients,and there was a difference between the two groups(I~2=98.3%,P<0.00001).The indirect comparison results showed that the efficacy of new combined androgen blockade was better than that of traditional combined androgen blockade in improving the overall survival of prostate cancer(HR=0.76,95%CI0.66 to 0.88,P=0.005);in terms of improving the progression free survival of prostate cancer,the efficacy of the new combined androgen blockade is better than that of the traditional combined androgen blockade(HR=0.52,95%CI 0.44 to 0.61,P=0.007)using flutamide and nilumide,which is equivalent to that of the traditional combined androgen blockade using bicalutamide(HR=1.05,95%CI 0.66 to 1.67,P=0.51).Conclusion:Combined androgen blockade can reduce the risk of death,delay disease progression and improve tumor response rate in patients with advanced prostate cancer.The new combined androgen blockade is better than the traditional combined androgen blockade,which is worthy of clinical application.Due to the lack of direct comparative evidence,the conclusions from the above indirect comparisons have yet to be validated by more high-quality prospective studies.