Surgical Management for Transposed Ovarian Recurrence of Cervical Cancer: A Systematic Review with Our Experience

Round 1

Reviewer 1 Report

Thank you for this thorough description of a case of recurrent cervical cancer in transposed ovaries managed by laparoscopic resection, and the accompanying review of the literature on the topic. The authors appear to have amassed the largest collection of such cases available in the literature. I believe the topic is relevant to the readership when considering when to leave ovaries in situ, how to follow these patients for recurrence, and surgical approach for managing recurrence in transposed ovaries. A few comments for consideration:

Content

I think many will question the purpose of leaving ovaries in situ in peri-menopausal patients with cervical cancer. If for fertility preservation (eg. future oocyte retrieval + surrogate) the fertility potential of the patient, including age, must be taken into account and weighed against oncologic safety of leaving ovaries in situ. If the purpose is for maintenance of hormonal function, why not consider hormone replacement? Perhaps patient preference?

I feel that appropriate case selection for ovarian preservation needs to be discussed further

- when is it safe to leave ovaries (histology, stage etc) and for what purpose?

 

Line 38,39- Consider adding more updated data on risk of ovarian metastases in adenocarcinomas of the cervix. See: Omar Touhami, Marie Plante, Should ovaries be removed or not in (early-stage) adenocarcinoma of the uterine cervix: a review. Gynecol Oncol. 2015 Feb;136(2):384-8.doi: 10.1016/j.ygyno.2014.12.011.

 

Line 76- pT1B1N0M0 is TNM staging (not FIGO). Also, do you mean FIGO 2018 or 2009 staging (not 2008)? You already mention pre-op staging in the paragraph above, consider putting everything in the first paragraph (beginning line 68).

Line 161- 2018 FIGO staging?

Lines 188-192- You state that based on the 3 resections after 2009 being done by laparoscopic approach and relatively long survival for these cases, laparoscopy is a reasonable approach. I think this is fair but you need to also acknowledge that these were the three cases with smallest tumour size. Did any people in your case series have other metastatic disease, apart from in the ovaries? Would be important to mention this.

Lines 225-227- ‘A recent report showed that ovarian preservation in premenstrual patients was more beneficial than oophorectomy for preserving ovarian function and reducing menopausal symptoms and recurrence risk [8].’ This sentence doesn’t make sense- of course leaving ovaries in situ (compared to oophorectomy) preserves ovarian function and reduces menopausal symptoms. Can you describe the study in more detail to give context?

Language

Line 18 (abstract)- should this read salpingectomy (not salpingotomy)?

 

Lines 47-49- Are you introducing data from a specific study here? Unclear. Consider removing the work ‘Additionally’ and introduce the study in question.

 

Line 99- Should this read ‘Laparoscopic bilateral oophorectomy was performed’ or ‘Laparoscopic resection of bilateral ovaries was performed’?

 

Line 105- Get rid of the word ‘However’.

 

Table 1- Consider changing ‘This study’ to ‘Present study’ or just primary author name, as you’ve done for the others. Also, add CC (? Chief complaint, clinical complaint) to the list of abbreviations for clarity.

 

Line 204- Consider change to present tense ie. Some gyne oncologist think/feel that ovarian metastasis has poor oncologic outcomes…

 

Line 247- Consider changing to ‘via the umbilicus in a plastic bag.’

 

Too many adverbs (eg. additionally, furthermore, therefore) that don’t necessarily fit the context. Consider getting rid of some of these to make it more concise.

Author Response

Response to Editor and the Reviewers’ comments

We would like to thank the Editor and the Reviewers for their helpful comments. The following are our point-by-point responses to the comments along with descriptions of the revisions made to the manuscript, which we have indicated using the “track changes” function of Microsoft Word.

 

Reviewer #1 comments

Thank you for this thorough description of a case of recurrent cervical cancer in transposed ovaries managed by laparoscopic resection, and the accompanying review of the literature on the topic. The authors appear to have amassed the largest collection of such cases available in the literature. I believe the topic is relevant to the readership when considering when to leave ovaries in situ, how to follow these patients for recurrence, and surgical approach for managing recurrence in transposed ovaries. A few comments for consideration:

 

Response:

We appreciate these useful comments from the Reviewer. We have revised the manuscript carefully according to the Reviewer’s comments. We believe the revised manuscript now addresses the Reviewer’s concerns.

 

Reviewer #1, Comment 1

I think many will question the purpose of leaving ovaries in situ in peri-menopausal patients with cervical cancer. If for fertility preservation (eg. future oocyte retrieval + surrogate) the fertility potential of the patient, including age, must be taken into account and weighed against oncologic safety of leaving ovaries in situ. If the purpose is for maintenance of hormonal function, why not consider hormone replacement? Perhaps patient preference?

 

I feel that appropriate case selection for ovarian preservation needs to be discussed further

 

- when is it safe to leave ovaries (histology, stage etc) and for what purpose?

 

Response: Lines 284-294, lines 297-301, lines 303-309, lines 311-321

We appreciate the reviewer’s insightful comments. A European retrospective, multi-center, observational cohort study compared the survival outcomes in women with early cervical cancer between ovarian conservation group and oophorectomy group. The study showed that women with ovarian conservation have better disease-free survival and less frequent menopausal symptoms compared to those who underwent oophorectomy with hormone replacement treatment. Therefore, we believe that ovarian conservation is merited for women with cervical cancer if oncologic risk is acceptable. We have added a description on this issue in the Discussion.

 

With regard to a possible candidate of ovarian preservation, we have provided a detailed discussion on this issue.

 

Reviewer #1, Comment 2

Line 38,39- Consider adding more updated data on risk of ovarian metastases in adenocarcinomas of the cervix. See: Omar Touhami, Marie Plante, Should ovaries be removed or not in (early-stage) adenocarcinoma of the uterine cervix: a review. Gynecol Oncol. 2015 Feb;136(2):384-8.doi: 10.1016/j.ygyno.2014.12.011.

 

Response: Lines 52-60

 

Thank you for your insightful comment. According to your suggestion, we have cited the recommended study and provided a brief summary of the results.

 

Reviewer #1, Comment 3

Line 76- pT1B1N0M0 is TNM staging (not FIGO). Also, do you mean FIGO 2018 or 2009 staging (not 2008)? You already mention pre-op staging in the paragraph above, consider putting everything in the first paragraph (beginning line 68).

 

Response: Line 91

As the reviewer suggested, we have moved the information regarding the pre-operative staging to the first paragraph of case description.

 

Reviewer #1, Comment 4

Line 161- 2018 FIGO staging?

 

Response: Line 188

We have revised the typo. Thank you.

 

Reviewer #1, Comment 5

Lines 188-192- You state that based on the 3 resections after 2009 being done by laparoscopic approach and relatively long survival for these cases, laparoscopy is a reasonable approach. I think this is fair but you need to also acknowledge that these were the three cases with smallest tumour size. Did any people in your case series have other metastatic disease, apart from in the ovaries? Would be important to mention this.

 

Response: Line 23, 112, 167, 380

 

We appreciate your helpful suggestions. As the reviewer suggested, we have clarified that our case did not have any other recurrence except for ovarian recurrence. Additionally, we have clarified that we included only the women with ovarian recurrence who had no other metastasis in our systematic review.

 

Regarding the systematic review, we agree with the reviewer’s opinion about the small tumor size of ovarian recurrence in women who were treated with laparoscopy. We have added this point as a limitation of this study.

 

Reviewer #1, Comment 6

Lines 225-227- ‘A recent report showed that ovarian preservation in premenstrual patients was more beneficial than oophorectomy for preserving ovarian function and reducing menopausal symptoms and recurrence risk [8].’ This sentence doesn’t make sense- of course leaving ovaries in situ (compared to oophorectomy) preserves ovarian function and reduces menopausal symptoms. Can you describe the study in more detail to give context?

Response: Lines 284-294

According to the reviewer’s suggestion, we have added more details about the cited study.

 

Reviewer #1, Comment 7

Language

 

Line 18 (abstract)- should this read salpingectomy (not salpingotomy)?

 

Response: Line 18

Thank you for your notification. We have revised the typo.

 

Reviewer #1, Comment 8

Lines 47-49- Are you introducing data from a specific study here? Unclear. Consider removing the work ‘Additionally’ and introduce the study in question.

 

Response: Line 48

 

We appreciate your helpful comment. We have introduced detailed information of the cited study.

 

Reviewer #1, Comment 9

Line 99- Should this read ‘Laparoscopic bilateral oophorectomy was performed’ or ‘Laparoscopic resection of bilateral ovaries was performed’?

 

Response: Line 122

 

Thank you for your comments. We have revised the text as you suggested.

 

Reviewer #1, Comment 10

Line 105- Get rid of the word ‘However’.

 

Response: Line 128

 

We have removed the word “However.”

 

Reviewer #1, Comment 11

Table 1- Consider changing ‘This study’ to ‘Present study’ or just primary author name, as you’ve done for the others. Also, add CC (? Chief complaint, clinical complaint) to the list of abbreviations for clarity.

 

Response: Table 1

Thank you for your comments. Per your suggestion, we have revised Table 1.

 

Reviewer #1, Comment 12

Line 204- Consider change to present tense ie. Some gyne oncologist think/feel that ovarian metastasis has poor oncologic outcomes…

 

Response: Line 241

Per your suggestion, we have revised the text to present tense.

 

Reviewer #1, Comment 13

Line 247- Consider changing to ‘via the umbilicus in a plastic bag.’

 

Response: Line 340

We have revised the text accordingly.

 

 

Reviewer #1, Comment 14

Too many adverbs (eg. additionally, furthermore, therefore) that don’t necessarily fit the context. Consider getting rid of some of these to make it more concise.

 

Response: We have meticulously proofread the entire manuscript to improve grammar, including avoiding too many adverbs.

 

We have revised the main text accordingly.

Reviewer 2 Report

Dear editor,

 

i read with interest the study of Maeda et al which is interesting and deserves publication. Minor changes are requested prior to its publication though.

1) the authors should ideally contact professor Morice and try to recover information concerning the OS and PFS of the two patients that were included in their SR

2)I would personally prefer if the authors would have searched SCOPUS and EMBASE as well.

3) A Kaplan Meier analysis would significantly enhance the scientific merit of the paper

 

Author Response

Reviewer #2 comments

i read with interest the study of Maeda et al which is interesting and deserves publication. Minor changes are requested prior to its publication though.

 

Response:

We appreciate the positive comments from the Reviewer. We have improved the manuscript according to the Reviewer’s comments. We believe the revised manuscript now addresses the Reviewer’s concerns.

 

 

Reviewer #2, Comment 1

1) the authors should ideally contact professor Morice and try to recover information concerning the OS and PFS of the two patients that were included in their SR

 

Response: Lines 382-385

Thank you for your helpful comment. We sent an e-mail to Professor Dr. Morice; however, we have not received his reply. We have added this point as a limitation of this study.

 

Reviewer #2, Comment 2

2)I would personally prefer if the authors would have searched SCOPUS and EMBASE as well.

 

Response: Lines 387-389

Thank you for your helpful comment. In our systematic literature search, we used SCOPUS but not EMBASE. We could not use EMBASE in our institution, and we have added this point as a limitation of the study.

 

Reviewer #2, Comment 3

3) A Kaplan Meier analysis would significantly enhance the scientific merit of the paper

 

Response: We have added Figure 4 to show the survival curve estimates based on surgical approaches.

 

We agree with your suggestion and we have added a Kaplan–Meier analysis in the revised manuscript.

Reviewer 3 Report

Please more clearly what is the reason to exclude a high number of initially selected articles. Don’t you think that a higher number of articles analyzed would improve the study quality?

Author Response

Reviewer #3 comments

Reviewer #3, Comment 1

Please more clearly what is the reason to exclude a high number of initially selected articles. Don’t you think that a higher number of articles analyzed would improve the study quality?

 

Response: Lines 161-162

We appreciate the helpful comments from the Reviewer. We have added more description regarding the initial selection of articles during the systematic search of literature.