Response: Second curettage versus conventional chemotherapy in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses for patients with gestational trophoblastic neoplasia: A systematic review and meta‐analysis

We really appreciate the considerate observation and thoughtful comments from the esteemed readers. Firstly, we had the same concerns before initiating the performance of our study, as we wrote to the corresponding author but no response was received. Under such circumstances, as we have stated in our manuscript, the two studies1, 2 had a different study period (2012–2014 vs 2014–2015) and different study participants (31 for experiment and 31 for control vs 26 for experiment and 26 for control), hence we deemed that it would be reasonable to conclude that the data of these two studies were not the same. Secondly, the search strategies of our study were developed using both controlled vocabulary and plain language in order to broaden the search. The details of the search strategies have been attached as supplementary files in our manuscript. It should be noted that the literature search of our study has been conducted from the inception of each database to January 31, 2023. The two studies which were believed to be “conspicuously absent” have been published in March 20233 and September 2023.4 Thirdly, combination of RCTs with non-RCTs in a meta-analysis has been reported5-9 and its methodology has been well established.10-13 Therefore, we believe that it is a useful tool to synthesize the results of RCTs and non-RCTs, especially when there are limited RCTs pertaining to therapeutic effects of second curettage for GTN. Moreover, in order to test the bias, we conducted subgroup analysis based on study location (developing country versus developed country) and study design (RCTs vs non-RCTs). The results were presented in figures S1 and S2 in our manuscript, respectively. We also performed sensitivity analysis by omitting studies and the results were presented in figure 4 in our manuscript. For the convenience of the reader, we further conducted subgroup analysis by quality assessment, the results showed significant advantages of second curettage in comparison with conventional chemotherapy. It is noteworthy to mention that, despite one of the studies authored by Ayatollahi et al. being excluded, the overall pooled effect size of second curettage group had significant advantages over conventional chemotherapy group with an OR of 0.02 (95% CI: 0.00–0.07) and a low heterogeneity (I2 = 6%, P = 0.36) for avoiding unnecessary chemotherapy. Data were presented in Figure 1. Fourthly, the aim of our study was to evaluate the therapeutic effects of second curettage as compared with conventional chemotherapy hence the third curettage was not within the scope of our study. Additionally, our study was performed based on the framework of PICOS,14 according to which, we are not allowed to recruit patients who underwent a third curettage as the experiment group has been designed for patients who solely received a second curettage. Fifthly, the PROSPERO protocol in our manuscript has been mistyped and it should be CRD42023395122. We sincerely apologize for this negligence. None.