Title: Local Resection Versus Radical Resection After Neoadjuvant Chemoradiotherapy for
Patients with Locally Advanced Rectal Cancer: A Propensity-score Matched Cohort Analysis
Version: 5 Date: 24 Mar 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
Congratulations on the revised manuscript. It now offers a clearer information to the readership.
I believe there is still room for improvement. Please consider my following comments.
Major comments:
1) The authors improved significantly the manuscript with the revised PSM. However it does not
seem fair to exclude the 4 patients that had completion TME after Local Excision, due to ypT3.
According to the GRECCAR2 study (refs 9 and 10 of the manuscript), local excision and total
mesorectal excision had similar outcomes, except for the sub-group that had completion TME
after local excision. This last group did worst when compared to either LE or TME. In other
words, selection for LE is key, and these are the 4 patients where selection failed. Excluding
these 4 patients from the PSM means to exclude the ones that are at increased risk of unfavorable
outcomes, and therefore masking the true outcomes of the local excision group. Please do not
exclude the 4 patients that had completion TME from the analyses.
2) Please add a Table/Section in the Results with the pathological and oncological outcomes
of patients in both groups after PSM pairing. How many were ypT0,1,2 or 3? How many of
the TME patients were ypN+? What about margins? How many local recurrence, systemic
recurrences, deaths in both groups? How many patients had completion TME performed after
LE?
3) Does pathological outcomes had any impact on the risk of OS and DFS? Please add it to the
Cox regression analyses.
Minor comments:
1) Introduction, Page 3: ”Several studies described the effect of LR in patients who significantly
downstage to nCRT for LARC. “
Discussion: "Accordingly, a closer 3-year follow-up plan should be established and strictly
enforced for LR patients "
Does this sentence refer to local recurrence or local resection? Is LR correct here? Perhaps using
LR as an abbreviation is not a good option as it seems to confunde also the authors. Do not use
LR as abbreviation, please.
2) Introductino, last paragraph "the samples of multiple previous randomized trials were both
small [9-10] “. Please exclude this sentence, this is one single randomized trial presenting
primary endpoint in one publication and long-term outcomes in the second publication. Also,
this is study had a sample size calculated and the planned amount of patients was obtained.
Therefore it is misleading the statement presented here. Please exclude it.
3) Methods, Inclusion/exclusion criteria, 2) Please, clarify when the re-evaluation was
performed. Last DAY of radiotherapy? Clarify the sentence “after the last nCRT”
4) Results, Survival Outcomes. “all log-rank P<0.001”, do the authors mean all p>0.05?
Considering that in the figure none of the p values were <0.001.
5) I am curious to know exactly why the place you are based is an endemic area of rectal cancer,
"First, our data were obtained in an endemic area of rectal cancer in China; the characteristics
might differ in other areas.”. I am sure the majority of the readership will also be curious, can
the authors please expand this information?
6) “the longest follow-up time (107 months)”, this statement is misleading as the median follow-
up is 44 months. Please exclude this sentence.
7) Finally, I believe that having the manuscript revised by an English natural speaker will
improve it.
Title: Local Resection Versus Radical Resection After Neoadjuvant Chemoradiotherapy for
Patients with Locally Advanced Rectal Cancer: A Propensity-score Matched Cohort Analysis
Version: 5 Date: 24 Mar 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
Congratulations on the revised manuscript. It now offers a clearer information to the readership.
I believe there is still room for improvement. Please consider my following comments.
Major comments:
1) The authors improved significantly the manuscript with the revised PSM. However it does not
seem fair to exclude the 4 patients that had completion TME after Local Excision, due to ypT3.
According to the GRECCAR2 study (refs 9 and 10 of the manuscript), local excision and total
mesorectal excision had similar outcomes, except for the sub-group that had completion TME
after local excision. This last group did worst when compared to either LE or TME. In other
words, selection for LE is key, and these are the 4 patients where selection failed. Excluding
these 4 patients from the PSM means to exclude the ones that are at increased risk of unfavorable
outcomes, and therefore masking the true outcomes of the local excision group. Please do not
exclude the 4 patients that had completion TME from the analyses.
2) Please add a Table/Section in the Results with the pathological and oncological outcomes
of patients in both groups after PSM pairing. How many were ypT0,1,2 or 3? How many of
the TME patients were ypN+? What about margins? How many local recurrence, systemic
recurrences, deaths in both groups? How many patients had completion TME performed after
LE?
3) Does pathological outcomes had any impact on the risk of OS and DFS? Please add it to the
Cox regression analyses.
Minor comments:
1) Introduction, Page 3: ”Several studies described the effect of LR in patients who significantly
downstage to nCRT for LARC. “
Discussion: "Accordingly, a closer 3-year follow-up plan should be established and strictly
enforced for LR patients "
Does this sentence refer to local recurrence or local resection? Is LR correct here? Perhaps using
LR as an abbreviation is not a good option as it seems to confunde also the authors. Do not use
LR as abbreviation, please.
2) Introductino, last paragraph "the samples of multiple previous randomized trials were both
small [9-10] “. Please exclude this sentence, this is one single randomized trial presenting
primary endpoint in one publication and long-term outcomes in the second publication. Also,
this is study had a sample size calculated and the planned amount of patients was obtained.
Therefore it is misleading the statement presented here. Please exclude it.
3) Methods, Inclusion/exclusion criteria, 2) Please, clarify when the re-evaluation was
performed. Last DAY of radiotherapy? Clarify the sentence “after the last nCRT”
4) Results, Survival Outcomes. “all log-rank P<0.001”, do the authors mean all p>0.05?
Considering that in the figure none of the p values were <0.001.
5) I am curious to know exactly why the place you are based is an endemic area of rectal cancer,
"First, our data were obtained in an endemic area of rectal cancer in China; the characteristics
might differ in other areas.”. I am sure the majority of the readership will also be curious, can
the authors please expand this information?
6) “the longest follow-up time (107 months)”, this statement is misleading as the median follow-
up is 44 months. Please exclude this sentence.
7) Finally, I believe that having the manuscript revised by an English natural speaker will
improve it.
Please review this paper.
user
Title: Local Resection Versus Radical Resection After Neoadjuvant Chemoradiotherapy for
Patients with Locally Advanced Rectal Cancer: A Propensity-score Matched Cohort Analysis
Version: 5 Date: 24 Mar 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
Congratulations on the revised manuscript. It now offers a clearer information to the readership.
I believe there is still room for improvement. Please consider my following comments.
Major comments:
1) The authors improved significantly the manuscript with the revised PSM. However it does not
seem fair to exclude the 4 patients that had completion TME after Local Excision, due to ypT3.
According to the GRECCAR2 study (refs 9 and 10 of the manuscript), local excision and total
mesorectal excision had similar outcomes, except for the sub-group that had completion TME
after local excision. This last group did worst when compared to either LE or TME. In other
words, selection for LE is key, and these are the 4 patients where selection failed. Excluding
these 4 patients from the PSM means to exclude the ones that are at increased risk of unfavorable
outcomes, and therefore masking the true outcomes of the local excision group. Please do not
exclude the 4 patients that had completion TME from the analyses.
2) Please add a Table/Section in the Results with the pathological and oncological outcomes
of patients in both groups after PSM pairing. How many were ypT0,1,2 or 3? How many of
the TME patients were ypN+? What about margins? How many local recurrence, systemic
recurrences, deaths in both groups? How many patients had completion TME performed after
LE?
3) Does pathological outcomes had any impact on the risk of OS and DFS? Please add it to the
Cox regression analyses.
Minor comments:
1) Introduction, Page 3: ”Several studies described the effect of LR in patients who significantly
downstage to nCRT for LARC. “
Discussion: "Accordingly, a closer 3-year follow-up plan should be established and strictly
enforced for LR patients "
Does this sentence refer to local recurrence or local resection? Is LR correct here? Perhaps using
LR as an abbreviation is not a good option as it seems to confunde also the authors. Do not use
LR as abbreviation, please.
2) Introductino, last paragraph "the samples of multiple previous randomized trials were both
small [9-10] “. Please exclude this sentence, this is one single randomized trial presenting
primary endpoint in one publication and long-term outcomes in the second publication. Also,
this is study had a sample size calculated and the planned amount of patients was obtained.
Therefore it is misleading the statement presented here. Please exclude it.
3) Methods, Inclusion/exclusion criteria, 2) Please, clarify when the re-evaluation was
performed. Last DAY of radiotherapy? Clarify the sentence “after the last nCRT”
4) Results, Survival Outcomes. “all log-rank P<0.001”, do the authors mean all p>0.05?
Considering that in the figure none of the p values were <0.001.
5) I am curious to know exactly why the place you are based is an endemic area of rectal cancer,
"First, our data were obtained in an endemic area of rectal cancer in China; the characteristics
might differ in other areas.”. I am sure the majority of the readership will also be curious, can
the authors please expand this information?
6) “the longest follow-up time (107 months)”, this statement is misleading as the median follow-
up is 44 months. Please exclude this sentence.
7) Finally, I believe that having the manuscript revised by an English natural speaker will
improve it.
assistant