Reviewers' comments:

Reviewer 1:

The authors provide a retrospective single-institution review of the use of pelvic

exenterations for recurrent cervical cancer after definitive treatment with radiation or
chemoradiation. They have a substantial number of patients at 480, however they are
spread across more than 50 years, time during which the landscape of cervical cancer
diagnosis, imaging, and treatment have changed radically.
I have major concerns regarding the grammar/language of the manuscript, which is at
times incomprehensible. It is also confusing that many of the abbreviations are not
defined within the text. In addition to editing, I do not believe that this paper adds much
to our knowledge about pelvic exenterations. The authors mention a separate publication
of the prognostic factors for survival for this patient population, which may make this
manuscript for interesting if included here. Additionally, the authors mention a Kaplan-
Meier analysis, and I would recommend instead of Figure 2, which is difficult to interpret.
It would also potentially help to get a sense of the loss to follow up for patients.
There are some interesting findings such as the expected decrease in perioperative
mortality and in the number of exenterations performed. It would require major editing
and adding some additional data, such as prognostic factors

Reviewer 2: (Q) is marked where questions are raised.

This manuscript contains many patients who have undergone exenteration for persistent
or residual cervix cancer. been the main objective of this report. However, The toxicity
reporting appears to have the objectives have not been clearly defined. (Q)
Results: all patients (1082) had undergone laparotomy of these 480 were suitable for PE.
Line 122 showing (10.6%) appears to be an error. (Q)
It is not stated as to how many resected specimens had clear resection margin. (Q) Since
positive resection margin relates both to recurrence as well as complications.
Table 4 shows decreased mortality for the years 1966-1979 155 with 27/171, (15.7%)
deaths and the lowest figures, for the periods 2000-2018 with 2/103 (1.9%) 156 deaths.
P=0.0003.
Fig 1 shows no significant difference was noted in mortality between the type of surgery.
By type of exenteration performed mortality was 28/234 (11.9%) for TPE, 21/236 165
(8.9%) for APE, (P = 0.277) and 0/10 in PPE.
Improved surgery and postoperative care as well as patient selection would be the reason
for decreasing mortality. However, corresponding complication rates appears to fluctuate
in 86/171 (50.2%), from 1966 to 1979; in 50/132 (37.8%) from the period 1980 to 1989; in
76/126 (59.5%) from 1990 to 2006 and 20/51 (39.2%) in the period 2008-2018.
The reason for this variation should be discussed. (Q) Since this is a retrospective study of
over 50 years missing medical records/notes would be a possibility.
Sub-heading terminology under section “RESULTS” (line 115) and “Treatment results”
(166) are confusing.
Line 166, 332 patients were without disease at the last follow- up. Is this correct? (Q)
If so, line 180, table 5 only shows patterns of recurrence in 91 patients! If the data on the
remaining patients who recurred is missing, how sure you can be that the patients with no
disease (332) likewise may have missing data? (Q)
Authors have extensively cited previous studies in the discussion, but readers would be
more interested in the discussion of your own result.
The discussion points will be type of residual disease and patient selection that you may
recommend PE based on YOUR experience that you learned over the years. A particularly
useful experience would be that, while you did select patients following laparotomy, still
selection may have been inappropriate and how you will use that knowledge (in light of
resected specimens) in refining your patient selection criteria, say using modern medical
imaging. You had mentioned PET scan (line 202) that can certainly tell you about disease
outside pelvis but for local extent of disease and to look at the tissue planes for local
resection MRI is indispensable.
Although the authors have mentioned in line 174 ‘The analysis of the prognostic factors
of this series will be the subject of another publication.” I think without this information
the present manuscript is incomplete.

Responses to Reviewers:

Reviewer No. 1:

Question 1 I have major concerns regarding the grammar/language of the manuscript, which is at
times incomprehensible

Answer: We send the company translation recommended by EJGO magazine

Question 2: It is also confusing that many of the abbreviations are not defined within the text.

Answer: We carefully reviewed that observation and made corrections to the text.

Question. In addition to editing, I do not believe that this paper adds much to our knowledge about
pelvic exenterations

Answer: The manuscript contains information related to the evolution of this treatment in terms of
morbidity and mortality, the problems in defining which cases should be considered for these
procedures and with the modifications suggested,the results of surgical treatment and its prognostic
factors. The study was carried out in a Latin American country where the disease has constituted
and continues to constitute a serious health problem. It is added that there is no case study such as
the one presented here in the literature of the countries mentioned.

Question: The authors mention a separate publication of the prognostic factors for survival for this
patient population, which may make this manuscript for interesting if included here.
Answer From line 179-184 the factors that influenced the prognosis of this series were added.
These factors are shown in manuscript andTable 5. of the text and in lines 259-262 of the
discussion:

Question: . Additionally, the authors mention a Kaplan-Meier analysis, and I would recommend
instead of Figure 2

Answer: The following adjustments were made to the manuscript to resolve these questions.(lines
167-175) The Kaplan-Meier method showed that 332/480 patients (69.1%) had a follow up of 1 to
60 months without disease. Two hundred and eight patients (62.6 %) lost their controls during the
first 24 months after surgery with no evidence of disease.

Mean follow up of disease-free survival DFS for 332 patients was 24.2 months and overall survival
OS, 34.4 months. One hundred and sixty-nine patients (50.9%), had an Overall Survival of 25 to 60
and more months. Additional information was added to the content of figure 2 for better
understanding and its content was included in the text

Question:

There are some interesting findings such as the expected decrease in perioperative mortality and in
the number of exenterations performed. It would require major editing

Answer: These observations were resolved, adding more information in the discussion of the
manuscript: Lines 207-209; 214-220; 237-257 and 260-263.

Reviewer No. 2

Question 1.-: The toxicity reporting appears to have been the main objective of this report.
However, the objectives have not been clearly defined. (Q)

Answer: In the text at the end of the introduction the following lines were added as objectives of
the manuscript: . The objective of this publication is to show the place of PE in the treatment of
these patients based on the number of laparotomies performed for this purpose, its morbidity,
mortality, the results of surgical procedures (DFS) and (OS), as well as the causes of treatment
failures

(lines 73-75)

Question 2 Results: all patients (1082) had undergone laparotomy of these 480 were suitable for
PE. Line 122 showing (10.6%) appears to be an error. (Q)

Answer: The data was modified and noted in the text, lines 117-119

3. Results: Of the 1,082 operated patients, only 480 (44.3%) underwent PE, the number of which
has decreased over the years. From 1966 to 2006, 429 (89.3%) procedures were performed and Of
these 429 EPs, 51 (10.6%) were carried out in the 2008-2018 period.
Question 3: It is not stated as to how many resected specimens had clear resection margin. (Q)
Since positive resection margin relates both to recurrence as well as complications.

Answer: This variable was not found in the records analyzed. The prognostic factor R0 has been
included in recent publications for pelvic cancer

Question 4: Improved surgery and postoperative care as well as patient selection would be the
reason for decreasing mortality. However, corresponding complication rates appears to fluctuate in
86/171 (50.2%), from 1966 to 1979; in 50/132 (37.8%) from the period 1980 to 1989; in 76/126
(59.5%) from 1990 to 2006 and 20/51 (39.2%) in the period 2008-2018. The reason for this
variation should be discussed. (Q)

Answer: The decrease in complications and postoperative mortality observed over the years
we justify its due to a better selection of cases to perform these surgeries, based on morbidity and
mortality figures from the results reported in previous publications [Ref.14]. and a better biological
behavior of this neoplasm, to judicious use of the clinic for a better selection of the candidates for
these surgeries; by having modern imaging procedures prior to surgery, having a group of surgeons
with more experience to perform these formidable procedures, having modern anesthesia equipment
and anesthesiologists dedicated exclusively to the care of cancer patients; having new provisions for
trans and postoperative hemotransfusions, counting intensive care rooms, having new antibiotics,
and carrying out hospital discharges once patients are fully recovered from their surgeries.

we attribute it with (lines 235-241)

Question 5: Sub-heading terminology under section “RESULTS” (line 115) and “Treatment
results” (166) are confusing.

Answer: Line 123, the title Treatment results was modified, by results of surgical treatment.

Question 6: Line 166, 332 patients were without disease at the last follow- up. Is this correct? (Q)

If so, line 180, table 5 only shows patterns of recurrence in 91 patients! If the data on the remaining
patients who recurred is missing, how sure you can be that the patients with no disease (332)
likewise may have missing data? (Q)

Answer: Treatment failure was demonstrated in 91 patients. This evolution was not found in the
remaining 241 patients.

The following adjustments were made to the manuscript to resolve these questions.(lines 167-175).

The Kaplan-Meier method showed that 332/480 patients (69.1%) had a follow up of 1 to 60 months
without disease. Two hundred and eight patients (62.6 %) lost their controls during the first 24
months after surgery with no evidence of disease.
Mean follow up of disease-free survival DFS for 332 patients was 24.2 months and overall survival
OS, 34.4 months. Figure 2.One hundred and sixty-nine patients (50.9%), had an Overall Survival
of 25 to 60 and more months

Question 7 The discussion points will be type of residual disease and patient selection that you
may recommend PE based on YOUR experience that you learned over the years.

Answer: The recommendations for a better selection of patients who will undergo PEs were written
in Answer to question 4: These consist ofa better biological behavior of this neoplasm, to judicious
use of the clinic for a better selection of the candidates for these surgeries; by having modern
imaging procedures prior to surgery, having a group of surgeons with more experience to perform
these formidable procedures, having modern anesthesia equipment and anesthesiologists dedicated
exclusively to the care of cancer patients; having new provisions for trans and postoperative
hemotransfusions, counting intensive care rooms, having new antibiotics, and carrying out hospital
discharges once patients are fully recovered from their surgeries.

we attribute it with (lines 236-242).

Question 8: Although the authors have mentioned in line 174 ‘The analysis of the prognostic
factors of this series will be the subject of another publication.” I think without this information the
present manuscript is incomplete.

Answer: From line 179-184 the factors that influenced the prognosis of this series were added.
These factors are shown in manuscript andTable 5. of the text and in lines 259-262 of the
discussion:

Prognostic factors: Multivariate analysis for overall survival (Cox Regression) showed as a positive
influence in prognosis APE, p= 0.000, and with negative influence: PPE, p=0.000, Parametrial
invasion p=0.003, pelvic wall invasion, p=0.053 and uterine body invasion, p=0.000. Table 5