Strengths and weaknesses of the study
bleeding, fibroid, blood loss, TVU, fibroids
UTERINE FIBROID, BLEEDING, RECURRENCE, FIBROID, BLOOD LOSS, FIBROIDS
An important strength of this study is that it is the first RCT on PSA versus GA for hysteroscopic myomectomy. Secondly, it was a multicenter study, in which 14 hospitals in the Netherlands participated, resulting in generalizable results. Thirdly, sonographers evaluating the primary outcome were blinded for the treatment arm and surgeon’s evaluation, resulting in objective assessment of the primary outcome. Lastly, not only completeness of resection and safety were evaluated, but also other outcomes were assessed, such as (uterine fibroid related) quality of life, menstrual blood loss, and recovery with a 1-year follow-up period. Therefore, this study provides important information on the use of PSA for hysteroscopic myomectomy.The most important limitations were the choice of primary outcome, and the fact that our study proved to be underpowered. At design of the trial, it was hypothesized that PSA could lead to lower patient comfort and hereby inability to complete the procedure. Therefore, an outcome parameter as objective as possible for complete fibroid resection (TVU by a blinded sonographer) was chosen. However, it turned out that TVU after 6 weeks was not always accurate to evaluate completeness and success of the procedure. For example, when multiple fibroids were present, it was difficult for a blinded sonographer to assess if there was a remnant of a resected fibroid or if these fibroids had not been resected and were still expected to be present. Also, the presence of a small remnant lesion without any clinical consequences does not necessarily mean that the procedure was unsuccessful from a patient perspective. In retrospect, one could argue that reduction in menstrual bleeding or improvement in quality of life would have been a better primary outcome.Although the percentage of complete resections was similar in both groups, noninferiority was not demonstrated, as the study did not achieve the planned power of 90%. Based on expert opinion and literature, we estimated the percentage of incomplete resections at 2.5%. However, the use of different outcomes (such as surgical reintervention, reduction in bleeding, recurrence of fibroids or symptoms) for the definition of successful hysteroscopic myomectomy made it difficult to estimate this percentage. The actual percentage of incomplete resections in our study, however, was 11.8%. Therefore, the required sample size should have been larger to possibly demonstrate noninferiority. It is, however, reasonable to argue that the estimated risk difference of −1.01% between PSA and GA for completeness of resection is irrelevant from a clinical perspective. Moreover, the 95% CI of −10.36 to 8.34 shows that the outcome of PSA and GA is very comparable, in which hysteroscopic myomectomy under PSA could be up to 8% more effective and 10% less effective, a margin which—in many other studies—is often found acceptable.Despite the study’s power limitation, the Data and Safety Monitoring Board (DSMB) advised to continue the study as planned, since it would provide important data on many other outcomes and changing the primary outcome during the study period would have reduced the methodological quality.