Title: A preoperative nomogram predicting risk of lymph node metastasis for early-stage
cervical cancer
Version: 4 Date: 07 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This is an interesting study attempting to establish a  preoperative
nomogram based on clinical and pathological characteristics for nodal metastasis in early stage
cervical cancer.  This has potential to assist clinicians in surgical treatment planning balancing
risks and benefits.  The nomogram was derived from a large number of patient from a well
established data base.  Vigorous methodology and appropriate statistics were applied. Training
and internal validation data sets were used.  Also external validation from different multicenter
cohort were done to establish the external validity of the derived nomogram. A number of further
additional suggestions are listed below to strengthen the manuscript .
REQUESTED REVISIONS:
1. Line 56 : “ More advances in lymph node (LN) status evaluation must be improved.”  Suggest
revised to “ More advances in lymph node (LN) status evaluation are needed pre-operatively ”
2. Line 59 : Suggest adding a line saying – “adjuvant chemoradiation is often recommended if
lymph nodes are found to be positive post surgery” to be placed right after “reference 4”.
3. Line 62-63 : “ indications for LN dissection have not been established” need to be revised as
indications for nodal dissection had been clearly established in all current guidelines at time of
hysterectomy being stage 1A1 with lymphovascular space invasion and stage I A2-2 disease if
a primary surgical approach with a radical hysterectomy is chosen for early stage disease .
4. Line 67-68 : “Furthermore, the ability to identify low-risk patients may be useful in medical
decision management” - please expand on this statement.  How is this information used in
“medical decision management” according to the authors to be clear to the readers ??
5. Please clarify which variables were derived from the SEER database to construct the
nomogram and which variables were derived from “two experienced pathologists in the
respective hospital pathology department” ?
6. Line 114 : Please expand on the rationale for choosing the 5% cut off as being “low risk” ?
References 14-15 as quoted do not mention this cut off ?
7. Line 122 : Please clarify how “tumor size” is established - ?  Clinically ?  Radiologically ?
Pathologically
8. Line 133 to 134 : “An internal validation of the accuracy estimates was performed with 1,849
patients to obtain relatively unbiased estimates…” Please confirm if these 1,849 patients was
indeed derived from the SEER dataset ?
9. Line 199-200 : “age at diagnosis, histologic subtype, tumor grade, tumor size and FIGO stage”
were used in the established nomogram.  Please clarify how was stage defined ?  Clinical or
radiologically ?
10. Line 194-196 : Please clarify if the R-enabled Internet browser provide exact estimate of
LNM risk in the output for personalized treatment decision making.
11. Table 1 : Please clarify the difference between the two “validation set” .
12. In general, tumor grading in cervical cancer is not universally done. This likely had resulted
in  more than 8500 patients where this data was missing in the SEER dataset.  Furthermore it
would be inaccurate to grade tumor on a small biopsy preoperatively. Would the authors be
able to provide another nomogram without the use of tumor grading ?  This would improve the
applicability and adoption of this model.
ADDITIONAL REQUESTS/SUGGESTIONS:
See above