A Regional Experience of Adult Granulosa Cell Tumours: A Retrospective Analysis

Comments 1: Title (and lines 89, 122, 229, 257, 258, 299 and 313): By definition, cohort studies evaluate the effect of an exposure and ideally they should be conducted prospectively. Therefore, the term “retrospective cohort study” should be avoided and it should be replaced by e.g. “retrospective analysis

Response 1: Thank you for pointing this out. We agree with this comment. Therefore, we have replaced references to type of study with ‘retrospective analysis’.

Comments 2: Abstract, line 42: The last sentence (“This study was limited by retrospective data collection”) should be deleted.

Response 3: This has been deleted.

Comments 3: In line 113 the authors state that “The median age at diagnosis was 57 years”, whereas Table 1 shows that “the mean age at diagnosis” was 57 years. This is probably a typing error that should be corrected (unless there was normal distribution of data and in such a case more information regarding distribution of data should be provided in the “Materials and Methods” and the “Results” sections).

Response 3: Thank you for pointing this out. The table was a typing error and I have corrected it (changed to median).

Comments 4: In Table 1, primary surgical procedures should be provided in acronyms, the same acronyms used in Table 2.

Response 4: I have changed the table to include acronyms.

Comments 5: In Table 2, a line should be added at the top, explaining what each column presents.

Response 5: I have changed this.

Comments 6: Materials and Methods: It would be interesting to know more details about the background population. Please add the total number of patients with ovarian cancer and/or gynecological malignancies in the databases of the “six UK sites”, if possible.

Reponse 6: Unfortunately I do not have access to this information.

Comment 7: Materials and Methods and Results: It would be interesting to know the status of tumor markers of patients included in this analysis, especially the status of inhibin and the status of tumor markers of patients who suffered disease recurrence. Please add some information regarding the status tumor markers of patients included in this analysis, if possible.

Response 7: Unfortunately there will significant inconsistency with the availability of data on tumour markers and we did not have enough data to interpret. Added a sentence in results section to explain this (line 125) ‘Data on tumour markers including inhibin and CA-125 were collected where available but unfortunately this was not consistently available and therefore could not be analysed.’ 

Comments 1: This topic should be revised. What is the focus of this study? What kind of regional experience is there with adult granulosa cell tumors?

Response 1: Changes made throughout the manuscript to more clearly define objectives.

Comments 2: Objective, the authors have many findings after reviewing the records. But what is the primary aim of this article?

Response 2: This has edited and objectives stated more clearly in the methods section.

Comments 3: Add a figure of a study flow diagram to enhance the understanding of this study.

What types of statistical analysis did the authors employ in this retrospective study?

Response 3: I do not think that a flow diagram of the study will add any additional information as the steps to the study are simply identifying patients with AGCT and collecting their data. I have further described the statistical analysis.

Comments 4: Most are stage I diseases and should not only include stage IC; where are stages IA, IB, and other stages (II- IV)?

Response 4: Rates of all stages are illustrated in table 1. I have updated the body of text in the results section to make it clearer.

Comments 5: Please remove “Three had a subsequent pregnancy (Lines 31).

Response 5: I have changed this. ‘In the pre-menopausal group, 3/15 women (20.0%) went on to have a successful pregnancy.’

Comments 6: What else is in your primary management, except staging surgery (33/107; 30.8%), hysterectomy and bilateral salpingo-oophorectomy (BSO) (28/107; 26.2%), or conservation of an ovary (17/107; 15.9%)? (30.8+26.2+15.9=72.9%?)

Reponse 6: Full details of primary management are in the text and table 1. I have altered the text to make this clearer.

Comment 7: In Lines 32-33, how many cases were diagnosed with recurrent disease? Why are 15 patients not included in the total number (27 patients)?

Response 7: A total of 27 patients had recurrent disease. Of these 27, 15 had multiple (more than 1) separate episodes of recurrence.

Comment 7: In any operation, whether the lesions are completely removed is the most critical factor that directly affects prognosis, especially in cases of malignant tumors. The above sense should not be taken as the conclusion. The conclusion must be concise and accurately reflect the research's purpose.

Response 7: Thank you for your comment. We have made some changes to the conclusion.

Comment 8: How many cases do you use transvaginal ultrasound, combined with Doppler blood flow analysis, to aid in preoperative diagnosis? Is routine use or selective use? Do you agree that if routinely used, it could decrease the number of staging surgeries?

Response 8: Unfortunately information on pre-op imaging was not available in a way that meaningful comparisons on this could be drawn (multiple hospital trusts over long time period where practices have inevitably changed over time). Certainly accurate pre-operative imaging will have an impact on pre-operative suspicion and thus optimal operative planning.

Comment 9: In Table 1, what is IC undetermined? Please add an explanation under the table.

Response 9: Ic (undetermined) means that we were unable to establish whether the stage was Ic1 or Ic2. I have added an explanation to the table.

Comment 10: In Figure 1a, it seems too complicated. How about only presenting stages 1, 2, 3, and 4

Response 10: This has been done as we wanted to illustrate the spread of the substages.

Comment 11: Table 2 should be remade. The total numbers in the 'Number of recurrences', 'route of surgery', and 'Intra-operative surgical spill' are incorrect.

Response 11: The numbers in this table illustrate the number of recurrences for different groups which is why the denominators are different e.g. 8/60 patients with stage Ia disease have had a recurrence. Is there a way to demonstrate this that would be easier to understand?

Comment 12: In Figure 2, (a) and (b) are similar; maybe list one is enough.

Response 12: Thank you

Comment 13: Regarding postoperative treatment for cases of intraoperative cyst rupture and complete cyst removal, how do you think it should be monitored and tracked to prevent recurrence? Are there any differences between them?

Response 13: This is an interesting question. I don’t think there was a routine difference in management/follow-up for the majority of patients with intra-operative cyst rupture and as far as I can tell there is inconsistency in offering adjuvant treatment for this indication.