Title: OUTCOMES OF NEOADJUVANT CHEMOTHERAPY AND RADICAL
HYSTERECTOMY FOR LOCALLY ADVANCED CERVICAL CANCER AT KIGALI
UNIVERSITY TEACHING HOSPITAL, RWANDA: A RETROSPECTIVE DESCRIPTIVE
STUDY
Version: 1 Date: 11 Feb 2024
Reviewer's report:
Review of :
OUTCOMES OF NEOADJUVANT CHEMOTHERAPY AND RADICAL
HYSTERECTOMY FOR LOCALLY ADVANCED CERVICAL CANCER AT KIGALI
UNIVERSITY TEACHING HOSPITAL, RWANDA: A RETROSPECTIVE DESCRIPTIVE
STUDY
It was a pleasure to have the opportunity to review this important subject matter related to
cervical cancer. This is an important area of clinical research, especially in areas where there is
limited radiation therapy and high rates of cervical cancer.
I have several comments as I will state below. It is my opinion that after addressing these issues
in a revised manuscript, that this paper should be acceptable for publication:
Background:
1. Sentence 2 in the first paragraph. “Despite continued efforts and advancements in prevention
and treatment, cervical cancer remains the leading cause of cancer-related death in women in
sub-Saharan Africa (SSA) [3]. “ and Sentence 1 in the second paragraph: “In SSA, most women
present with advanced stage cervical cancer [5].”  These two sentences need to be tied together
to set the stage of why this research is so important. What efforts are not working and why are
they not working; and why is there still advanced stages of cervical cancer in this environment?
I just want you to just do a better job in briefly highlighting some of the problems that explain
these questions at the onset of your publication.
2. Sentence 2 in the second paragraph with use of the word “globally” I would be careful and
place a qualifier as you have described in other areas of the manuscript; ie… where there is
access to radiation therapy and chemotherapy (as you know this is often not readily available
in many sub-Saharan African countries).
3. Paragraph 3 second sentence you state that IIA1 is an early stage and patients were treated
with radical hysterectomy by the new gynecologic oncologist. However, you include this stage
in your current research group but exclude IA2 and IB1 from the analysis. Please explain why
you state these patients (IIA1) could and were treated with a radical hysterectomy by the new
gynecologic oncologist, but you still include them in this study (12 patients)? Why didn’t these
patients just have a radical hysterectomy? Depending on your explanation they may need to be
removed from the analysis or you can stratify the groups by stage related to outcomes as I will
suggest below in my other comments related to your results.
Methods
1. I know that you are using the FIGO 2009 staging criteria in your study; however, was there
any quantitative data on the size of the patients with IB2 lesions given that there were only 14
patients?
2. There is no description on what is meant by a radical hysterectomy. Are you doing a type 2
or a type 3 radical hysterectomy on the patients? Please indicate this and describe what is meant
by your classification.
3. What was the purpose of using the ultrasound? This was not clear. Was it to rule out
hydronephrosis? This needs to be stated in the methods section. If so how many patients were
identified to have stage III-B disease by ultrasound and were excluded? This needs to be stated
in the results section.
4. In general, how many patients were evaluated and excluded? Why were they excluded? This is
not clear in your methods. It appears you start with 57 patients but there had to me more patients
evaluated to get to this number. This needs to be documented in your methods and results section.
5. Your statement in paragraph 2 under “Treatment Protocol” is a bit confusing. What is meant by
“All eligible patients”? What is meant by eligible? Do you mean all patient that met the inclusion
criteria were then examined to determine eligibility for NACT? This needs to be cleared up and
relates back to my comment in #4 above.
Results
I would suggest you place numbers of patients in each stage that had a radical hysterectomy
instead of just percentages as you have done in the results section. Placing this in a table form
would be helpful.
Demographics
1. The demographics of the 38 patients who underwent radical hysterectomy would be
beneficial:
a. Layout stage related to reduction in size to NACT
b. Layout stage related to pathological findings (no residual disease - 5 patients, residual disease,
3 in lymph node status, 1 in adnexa and margins). You cannot understand the out come/efficacy
of the therapy without these specific demographics.
2. In the 5 patients who had clinical disease at the time of surgery:
a. Why did the nodes not get biopsied for verification?
b. If there was parametrical disease why was this not identified preoperatively? This is not a
criticism but this needs to be explained.
3. Second sentence in the 3rd paragraph is out of place. “Nine of the 43 (20.9%) surgical patients
were referred for adjuvant CRT based on high-risk intra-operative (n = 5/9) or final pathological
(n = 4/9) findings. Only 5/9 (55.6%) patients received CRT due to limited access to RT.” It
should be part of the 2nd paragraph and the 1st sentence in the 3rd paragraph should be included
in the 4th paragraph eliminating the 3rd paragraph.
4. Of the 40 patients who had follow up information please show the demographics of the 32
patients with no evidence of disease ( stage, response to NACT, post op path report details).
5. Of the 8 recurrences in the follow up group please also show their demographics as stated
in #4 above.
6. Please describe how 7 of the 8 were treated with curative surgery. What curative surgery did
they have? Did they all have the same operation? I am confused by the word curative if 5 died
of their disease. Please explain.
7. What is meant by this sentence and where is it describe in the manuscript? “There were
no documented recurrences among those who received adjuvant CRT.” Please explain who
this group of patients are in the manuscript. I am aware that 5 patients received post operative
CRT. Please give the demographics of these patients along with the other 8 patients who had
recurrences. This will give more clarity to the reader.
Discussion
1. This sentence you use in paragraph 3: “Additionally, subset analysis showed that 5-year DFS
for NACT-S versus CRT was not significantly different for stages IB2 and IIA, only for stage
IIB, suggesting this treatment approach is most appropriate for early locally advanced stage
disease [14]” I would suggest not using the words most appropriate because the data is limited
with small numbers as in your study. Therefore, I would indicate that based on current data
that this group of patient may have similar outcomes to CRT but could be affected by other
prognostic factors such as size, LVSI or lymph node status (which now upstages the patient to
stage III-C1 or 2. Additionally, we know that there are high recurrence rates in this population
of patients. This is why it is important for you to give the demographics of recurrences by stage
and pathological findings in your study.
I think this study is very much needed in the literature. This is why I made the detailed comments
in my review. Once these comments are addressed I feel this will be an important contribution
to the literature. The numbers are small, so I am not sure if the statistical analysis is of any
value given that other larger studies did not have the numbers to have enough power to make
an inference on the the differences in treatment modalities. However, as you have indicated that
there are major radiation deserts in sub-Saharan Africa, therefore it is important to understand
the alternatives that have to be implemented in such clinical ecosystem. I commend the authors
in their attempt to place this in the published domain and I look forward to reviewing the revised
manuscript.