Title: Local Resection Versus Radical Resection After Neoadjuvant Chemoradiotherapy for
Patients with Locally Advanced Rectal Cancer: A Propensity-score Matched Cohort Analysis
Version: 2 Date: 16 Feb 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
I appreciated reading this manuscript comparing total mesorectal excision (TME) vs. local
excision (LE) for rectal cancer after neoadjuvant therapy. The authors retrospectively accessed
a large number of patients, paired them using a propensity score analyses and performed
comparisons regarding long term outcomes. The main weakness here in my opinion is related
to the selection of patients for each group. I have pointed it out in the following lines:
Major concerns
1) The main challenge in recommending LE for a residual tumor is the selection of the ideal
candidates. Excluding patients that had positive nodes after TME from the analysis is an
important selection bias. These patients can not be excluded, as the nodes from the LE group
will never be accessed pathologically. Please do not exclude this group from the analyses.
2) Still regarding the exclusion criteria, please clarify the criteria “recurrent rectal cancer”. As
recurrence is one of the endpoints, it is not clear for me why/how to exclude these patients.
3) Regarding the inclusion criteria, it is not clear for me how to use the final pathological staging
as inclusion criteria. The authors should consider the re-assessment staging as inclusion criteria,
or even the baseline staging (as it was used in the previous randomized trials mentioned by the
authors refs 9,10 and 11). If the authors consider the final pathological staging as an inclusion
criteria it will again create an important selection bias, that will not allow this manuscript results
to be interpreted in favour or against local excision.
4) I disagree with the authors that local recurrence in the rectal wall after LE is “easy" to salvage.
There are evidence suggesting that patients with local recurrences after LE have a high risk of
+CRM and re-recurrence after salvage therapy(1), therefore not satisfactory salvaged by surgery.
Please include all local recurrence together in the analises.
5) Regarding the propensity score matched, it is not clear for me why the authors did not include
the features used to select a patient for LE, but pathological features. Previous randomized trial
(2) used baseline and re-assessment features to select patients for LE as baseline tumor size
and baseline staging, residual tumor size and residual tumor staging. All of these features were
excluded from the PSM calculated here, please clarify why. Also please, clearly describe why
the authors opted to use pathological features and serum markers here.
Minor comment:
1) Abstract: please review the following sentence, it is difficult to understand. ”In the matched
analyses, compared with the radical resection group (n=130), the local resection group (n=47)
of the OS (5-year: 88.0% vs. 86.7%; OR=0.626, p=0.437), DFS (5-year: 89.7% vs. 84.5%;
OR=0.693, p=0.441), LR (5-year: 8.2% vs. 6.4%; OR=1.012, p=0.987), DM (5-year: 7.2% vs.
12.5%; OR=0.657, p=0.657), the differences were not statistically significant and the tumor
distance to the anal very less than 10 cm in all patients. "
2) Refence 8 is not from a randomized trial of LE vs. TME after nCRT. In this study, only the
LE group had radiotherapy. Please exclude it from the last paragraph of the introduction.
3) Methods - Follow-up: Please, briefly describe how is the follow-up after radical resection
according to the national guideline. (First paragraph of this section)
4) Results must include the baseline features of the two groups. As all patients had re-assessment
magnetic resonance before resection, also re-assessment staging should be included.
5) The authors claim that this is the largest cohort of patients that have local recurrence after
nCRT compared to TME. However in the Greccar study 74 patients were treated with LE, while
here there was 56 patients. Please, review this statement.
6) Using various radiation treatment is a limitation of the study and needs to be clearly addressed
in the discussion.
References:
1 Perez RO, Habr-Gama A, Sao Juliao GP et al. Transanal Endoscopic Microsurgery (TEM)
Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for
Local Recurrence. Ann Surg Oncol 2016; 23: 1143-1148.
2 Rullier E, Rouanet P, Tuech JJ et al. Organ preservation for rectal cancer (GRECCAR 2): a
prospective, randomised, open-label, multicentre, phase 3 trial. Lancet 2017; 390: 469-479.
Title: Local Resection Versus Radical Resection After Neoadjuvant Chemoradiotherapy for
Patients with Locally Advanced Rectal Cancer: A Propensity-score Matched Cohort Analysis
Version: 2 Date: 16 Feb 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
I appreciated reading this manuscript comparing total mesorectal excision (TME) vs. local
excision (LE) for rectal cancer after neoadjuvant therapy. The authors retrospectively accessed
a large number of patients, paired them using a propensity score analyses and performed
comparisons regarding long term outcomes. The main weakness here in my opinion is related
to the selection of patients for each group. I have pointed it out in the following lines:
Major concerns
1) The main challenge in recommending LE for a residual tumor is the selection of the ideal
candidates. Excluding patients that had positive nodes after TME from the analysis is an
important selection bias. These patients can not be excluded, as the nodes from the LE group
will never be accessed pathologically. Please do not exclude this group from the analyses.
2) Still regarding the exclusion criteria, please clarify the criteria “recurrent rectal cancer”. As
recurrence is one of the endpoints, it is not clear for me why/how to exclude these patients.
3) Regarding the inclusion criteria, it is not clear for me how to use the final pathological staging
as inclusion criteria. The authors should consider the re-assessment staging as inclusion criteria,
or even the baseline staging (as it was used in the previous randomized trials mentioned by the
authors refs 9,10 and 11). If the authors consider the final pathological staging as an inclusion
criteria it will again create an important selection bias, that will not allow this manuscript results
to be interpreted in favour or against local excision.
4) I disagree with the authors that local recurrence in the rectal wall after LE is “easy" to salvage.
There are evidence suggesting that patients with local recurrences after LE have a high risk of
+CRM and re-recurrence after salvage therapy(1), therefore not satisfactory salvaged by surgery.
Please include all local recurrence together in the analises.
5) Regarding the propensity score matched, it is not clear for me why the authors did not include
the features used to select a patient for LE, but pathological features. Previous randomized trial
(2) used baseline and re-assessment features to select patients for LE as baseline tumor size
and baseline staging, residual tumor size and residual tumor staging. All of these features were
excluded from the PSM calculated here, please clarify why. Also please, clearly describe why
the authors opted to use pathological features and serum markers here.
Minor comment:
1) Abstract: please review the following sentence, it is difficult to understand. ”In the matched
analyses, compared with the radical resection group (n=130), the local resection group (n=47)
of the OS (5-year: 88.0% vs. 86.7%; OR=0.626, p=0.437), DFS (5-year: 89.7% vs. 84.5%;
OR=0.693, p=0.441), LR (5-year: 8.2% vs. 6.4%; OR=1.012, p=0.987), DM (5-year: 7.2% vs.
12.5%; OR=0.657, p=0.657), the differences were not statistically significant and the tumor
distance to the anal very less than 10 cm in all patients. "
2) Refence 8 is not from a randomized trial of LE vs. TME after nCRT. In this study, only the
LE group had radiotherapy. Please exclude it from the last paragraph of the introduction.
3) Methods - Follow-up: Please, briefly describe how is the follow-up after radical resection
according to the national guideline. (First paragraph of this section)
4) Results must include the baseline features of the two groups. As all patients had re-assessment
magnetic resonance before resection, also re-assessment staging should be included.
5) The authors claim that this is the largest cohort of patients that have local recurrence after
nCRT compared to TME. However in the Greccar study 74 patients were treated with LE, while
here there was 56 patients. Please, review this statement.
6) Using various radiation treatment is a limitation of the study and needs to be clearly addressed
in the discussion.
References:
1 Perez RO, Habr-Gama A, Sao Juliao GP et al. Transanal Endoscopic Microsurgery (TEM)
Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for
Local Recurrence. Ann Surg Oncol 2016; 23: 1143-1148.
2 Rullier E, Rouanet P, Tuech JJ et al. Organ preservation for rectal cancer (GRECCAR 2): a
prospective, randomised, open-label, multicentre, phase 3 trial. Lancet 2017; 390: 469-479.
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: 2 Date: 16 Feb 2023
Reviewer:  Guilherme Pagin São Juliao
Reviewer's report:
I appreciated reading this manuscript comparing total mesorectal excision (TME) vs. local
excision (LE) for rectal cancer after neoadjuvant therapy. The authors retrospectively accessed
a large number of patients, paired them using a propensity score analyses and performed
comparisons regarding long term outcomes. The main weakness here in my opinion is related
to the selection of patients for each group. I have pointed it out in the following lines:
Major concerns
1) The main challenge in recommending LE for a residual tumor is the selection of the ideal
candidates. Excluding patients that had positive nodes after TME from the analysis is an
important selection bias. These patients can not be excluded, as the nodes from the LE group
will never be accessed pathologically. Please do not exclude this group from the analyses.
2) Still regarding the exclusion criteria, please clarify the criteria “recurrent rectal cancer”. As
recurrence is one of the endpoints, it is not clear for me why/how to exclude these patients.
3) Regarding the inclusion criteria, it is not clear for me how to use the final pathological staging
as inclusion criteria. The authors should consider the re-assessment staging as inclusion criteria,
or even the baseline staging (as it was used in the previous randomized trials mentioned by the
authors refs 9,10 and 11). If the authors consider the final pathological staging as an inclusion
criteria it will again create an important selection bias, that will not allow this manuscript results
to be interpreted in favour or against local excision.
4) I disagree with the authors that local recurrence in the rectal wall after LE is “easy" to salvage.
There are evidence suggesting that patients with local recurrences after LE have a high risk of
+CRM and re-recurrence after salvage therapy(1), therefore not satisfactory salvaged by surgery.
Please include all local recurrence together in the analises.
5) Regarding the propensity score matched, it is not clear for me why the authors did not include
the features used to select a patient for LE, but pathological features. Previous randomized trial
(2) used baseline and re-assessment features to select patients for LE as baseline tumor size
and baseline staging, residual tumor size and residual tumor staging. All of these features were
excluded from the PSM calculated here, please clarify why. Also please, clearly describe why
the authors opted to use pathological features and serum markers here.
Minor comment:
1) Abstract: please review the following sentence, it is difficult to understand. ”In the matched
analyses, compared with the radical resection group (n=130), the local resection group (n=47)
of the OS (5-year: 88.0% vs. 86.7%; OR=0.626, p=0.437), DFS (5-year: 89.7% vs. 84.5%;
OR=0.693, p=0.441), LR (5-year: 8.2% vs. 6.4%; OR=1.012, p=0.987), DM (5-year: 7.2% vs.
12.5%; OR=0.657, p=0.657), the differences were not statistically significant and the tumor
distance to the anal very less than 10 cm in all patients. "
2) Refence 8 is not from a randomized trial of LE vs. TME after nCRT. In this study, only the
LE group had radiotherapy. Please exclude it from the last paragraph of the introduction.
3) Methods - Follow-up: Please, briefly describe how is the follow-up after radical resection
according to the national guideline. (First paragraph of this section)
4) Results must include the baseline features of the two groups. As all patients had re-assessment
magnetic resonance before resection, also re-assessment staging should be included.
5) The authors claim that this is the largest cohort of patients that have local recurrence after
nCRT compared to TME. However in the Greccar study 74 patients were treated with LE, while
here there was 56 patients. Please, review this statement.
6) Using various radiation treatment is a limitation of the study and needs to be clearly addressed
in the discussion.
References:
1 Perez RO, Habr-Gama A, Sao Juliao GP et al. Transanal Endoscopic Microsurgery (TEM)
Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for
Local Recurrence. Ann Surg Oncol 2016; 23: 1143-1148.
2 Rullier E, Rouanet P, Tuech JJ et al. Organ preservation for rectal cancer (GRECCAR 2): a
prospective, randomised, open-label, multicentre, phase 3 trial. Lancet 2017; 390: 469-479.
assistant