Different therapeutic regimens in the treatment of metastatic prostate cancer

Dear Editor, With great interest, we read an article entitled ‘Different therapeutic regimens in the treatment of metastatic prostate cancer’ in your precious journal1. This meta-analysis included 17 observational studies to conduct a network meta-analysis to compare the efficacy of different therapeutic regimens for metastatic prostate cancer. They had a conclusion that local treatment (radical prostatectomy or radiation therapy) could provide a relatively favorable survival rate in comparison with systematic therapies [no local therapy, deprivation therapy, ADT (androgen deprivation therapy) and ADT+Chemo]. Nevertheless, there were several raised queries in the meta-analysis. First, in the methods of the meta-analysis for statistical analysis, the author wrote, ‘The Chi-square test and I-square test were applied to assess the heterogeneity; If I2 >50% or Chi-square test P>0.10, it was deemed to existing significant heterogeneity’, while this method was not recommended by Cochrane Handbook for the heterogeneity judgement. The recommended instruction was that the heterogeneity between studies should be based on the difference of clinical data in each study from the reviewers’ judgement before the action of the pooled analysis2. Second, most of the included studies were non-randomized controlled trials; even if the included observational studies with a large sample size can reflect the disease state in the real world, there was a huge difference in the sample size between the treatment arm and control arm for most of the included studies in the article. In most studies, the treatment arm has a very small sample size compared to the control group. The difference may result in a bias for the outcomes. We did not know which type these included observational studies belong to because there were various study types, such as retrospective cohort study, retrospective comparative study, comparative study, and propensity score matched study, which can be a source of heterogeneity among studies. Third, three clinical endpoints (overall survival, cancer-specific mortality, or all-cause mortality) were compared comprehensively. Nevertheless, there was an important item that follow-up time for the clinical endpoints should be known and analyzed because it has an important effect on the clinical endpoints of the included studies, which was also the important source of heterogeneity among studies3. Ethical approval Our submitted manuscript does not involve any patients without the ethical approval document. Consent Our submitted manuscript does not involve any patients without the written informed consent documents. Sources of funding The Grants from the National Natural Science Foundation of China (82160577); Key Program for Regional Joint Funds of Natural Science Foundation of Guangdong Province (Nos. 2020B1515120094 and 2021B1515120053); The Program for Science and Technology Project of Guizhou Province, Qiankehe Platform Talents (No. [2021] 5613); The Key Program for Science and Technology Project of Guizhou Province (No. ZK [2021] 007); Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province (No. 20204BCJL23051). Author contribution Shuai H. and Sheng H.: equally participated in the original idea and writing of the first draft; J.P. and Z.L.: did figure production and data correction; Y.T. and Q.W.: edited the final manuscript. All authors approved the last version of this manuscript. Conflicts of interest disclosure There are no conflicts of interest among the authors. Research registration unique identifying number (UIN) None. Guarantor All authors. Data availability statement The supporting data used in the paper can be obtained via the requirement from the authors Yubo Tang and Qingde Wa. Provenance and peer review Commentary, internally reviewed.