Controversies in the Staging of Patients with Locally Advanced Cervical Cancer
Round 1
Reviewer 1 Report
Without comments. In this work form (and authors contribut. implementation) my comment: accept with all componentns of review articles and discussion with recently published works.
Author Response
Thank you for the reviewer's comment.
Sincerely,
Janos L. Tanyi MD PhD
Reviewer 2 Report
This study aimed to review the controversies in the staging of patients with locally advanced cervical cancer and summarize the available literature. This review articles is well written and discussed most of the relevant points in this field. I have some comments to the authors.
1. Page 6, Line 263-264: The EMBRACE-II selects patients to receive prophylactic para-aortic radiotherapy based on the number and location of pelvic lymph nodes (i.e. at least 3 pelvic lymph nodes or common iliac nodes). The upper extent of prophylactic radiotherapy is set at the left renal vein. Although the EMBRACR-II study is still undergoing, One previous study had reported the benefit of prophylactic para-aortic radiotherapy based on these criterias (Gynecol Oncol. 2018 Feb;148(2):291-298). I would suggest the authors to briefly summarize the potential impact of risk-based para-aortic radiotherapy in this paragraph.
2. The delineation of para-aortic region is also critical to achieve optimal therapeutic ratio of para-aortic radiotherapy. However, the optimal delineation of para-aortic radiotherapy remains unclear. The authors may also need to discuss about the relevance of precise delineation of para-aortic region in the section of radiotherapy (Int J Radiat Oncol Biol Phys. 2013;85:1045-50; Radiother Oncol. 2018;127:417-22; Int J Gynecol Cancer. 2022 May 3;32(5):606-612).
Author Response
Comment 1. Page 6, Line 263-264: The EMBRACE-II selects patients to receive prophylactic para-aortic radiotherapy based on the number and location of pelvic lymph nodes (i.e. at least 3 pelvic lymph nodes or common iliac nodes). The upper extent of prophylactic radiotherapy is set at the left renal vein. Although the EMBRACR-II study is still undergoing, One previous study had reported the benefit of prophylactic para-aortic radiotherapy based on these criterias (Gynecol Oncol. 2018 Feb;148(2):291-298). I would suggest the authors to briefly summarize the potential impact of risk-based para-aortic radiotherapy in this paragraph.
Reply to comment 1: We have summarized the study mentioned by the reviewer and the potential impact of risk-based para-aortic radiation therapy in the discussion (lines 283-325).
Comment 2. The delineation of para-aortic region is also critical to achieve optimal therapeutic ratio of para-aortic radiotherapy. However, the optimal delineation of para-aortic radiotherapy remains unclear. The authors may also need to discuss about the relevance of precise delineation of para-aortic region in the section of radiotherapy (Int J Radiat Oncol Biol Phys. 2013;85:1045-50; Radiother Oncol. 2018;127:417-22; Int J Gynecol Cancer. 2022 May 3;32(5):606-612).
Reply to comment 2: Thank you for the excellent comment, we further discuss the relevance of precise delineation of the para-aortic region (lines 349-365)
Reviewer 3 Report
Dear authors,
Exhaustive and comprehensive revision of literature has been made regarding the surgical staging of locally advance cervical cancer. This topic is currently under discussion with the controversy of performing surgical para-aortic staging or not.
Recent evidence, very well summarized in the article, suggests no oncological impact when performing surgical staging. However, new prospective randomized trials are proposing the same rationale than older studies.
A new rationale about the role of prophylactic extended field radiation therapy has been summarized too with interesting findings. I would strongly suggest to develop widely this part of the article. The authors mentioned that: at least 3 lymph nodes or a common iliac lymph node suspected on imaging, are risk factors to consider extended radiation according EMBRACE II. I encourage authors to review those factors associated with higher risk of recurrence when extended radiation may be indicated such us: bilateral lymph nodes, persistent disease in cervix after primary radio chemotherapy.
Sincerely
Author Response
Comment 1: A new rationale about the role of prophylactic extended field radiation therapy has been summarized too with interesting findings. I would strongly suggest to develop widely this part of the article. The authors mentioned that: at least 3 lymph nodes or a common iliac lymph node suspected on imaging, are risk factors to consider extended radiation according EMBRACE II. I encourage authors to review those factors associated with higher risk of recurrence when extended radiation may be indicated such us: bilateral lymph nodes, persistent disease in cervix after primary radio chemotherapy.
Reply to comment 1: thank you for an excellent comment we have reviewed other risk factors that are associated with risk of para-aortic lymph node metastases and possible benefit from extended field radiation therapy (lines 283-325).
Sincerely,
Janos L. Tanyi MD PhD
Reviewer 4 Report
The authors make an updated review of the articles on "the Staging of Patients with Locally Advanced Cervical Cancer" classifying it into different parts that are very clarifying for the reader:
1º Imaging Techniques for Clinical Staging of Locally Advanced Cervical Cancer.
2º Data from Retrospective Studies on the Role of Surgical Staging.
3rd Data from Randomized Controlled Trials on the Role of Surgical Staging.
4th Data from Randomized Controlled Trials on the Role of Surgical Staging.
5th Role of Prophylactic Extended Field Radiation Therapy.
We endorse the points in which the authors conclude that surgical staging can identify patients with microscopic metastases in the para-aortic lymph nodes while excluding false-positive cases. We accurately delineate radiation fields and avoid the long-term morbidity and complications associated with external beam radiotherapy.
High-volume case centers and experienced surgeons are the mandatory pairing so that surgical staging is not associated with significant morbidity or unjustified delay in the initiation of definitive chemoradiotherapy.
Given the increased use of IMRT intensity-modulated radiation therapy which is associated with less toxicity, future studies should demonstrate whether surgical staging impacts patients' quality of life in addition to oncological outcomes.
Author Response
Thank you for the reviewer's comments.
Sincerely,
Janos L. Tanyi MD PhD
Round 2
Reviewer 2 Report
The authors had nicely revised manuscript. Thank you!
