Title: Primary Tumor Resection with or without Metastasectomy for Left- and Right-sided Stage
IV Colorectal Cancer: An Instrumental Variable Analysis
Version: 1 Date: 11 Jan 2022
Reviewer's report:
In this study, Ling Yin et al. have evaluated the associations between primary tumor resection
(with or without metastasectomy) and survival in left- and right-sided stage IV colorectal cancer.
I think the research aim is relevant, and the study design seems appropriate to address that. The
epidemiological/statistical analyses seem suitable for the task, but they are quite complex, and
I think that a separate review by an epidemiologist would be useful. I think the manuscript is
quite well-written. I have just a few minor suggestions to improve the manuscript:
1. I would recommend being more cautious with implying causation (such as page 27, line 21;
"Our instrumental variable analysis shows tat PTR does not improve survival..."), considering
that this retrospective study can only show associations, not causation. Please review the whole
manuscript and reconsider such conclusions.
2.  The word"splenic" is missing from "... left-sided CRC occurs in flexure, ..." (page 5, line 21).
3. Please consider, whether all abbreviations are necessary. In my opinion, the abbreviations
make this text more difficult to read. Moreover, some abbreviations are very similar (e.g., PTL,
PTR), which further complicates the text.
4. I would recommend adding version numbers for R packages used in the study.
5. I would recommend systematically using italics for gene names (e.g., KRAS, BRAF) to
separate them from gene products.
Title: Primary Tumor Resection with or without Metastasectomy for Left- and Right-sided Stage
IV Colorectal Cancer: An Instrumental Variable Analysis
Version: 1 Date: 11 Jan 2022
Reviewer's report:
In this study, Ling Yin et al. have evaluated the associations between primary tumor resection
(with or without metastasectomy) and survival in left- and right-sided stage IV colorectal cancer.
I think the research aim is relevant, and the study design seems appropriate to address that. The
epidemiological/statistical analyses seem suitable for the task, but they are quite complex, and
I think that a separate review by an epidemiologist would be useful. I think the manuscript is
quite well-written. I have just a few minor suggestions to improve the manuscript:
1. I would recommend being more cautious with implying causation (such as page 27, line 21;
"Our instrumental variable analysis shows tat PTR does not improve survival..."), considering
that this retrospective study can only show associations, not causation. Please review the whole
manuscript and reconsider such conclusions.
2.  The word"splenic" is missing from "... left-sided CRC occurs in flexure, ..." (page 5, line 21).
3. Please consider, whether all abbreviations are necessary. In my opinion, the abbreviations
make this text more difficult to read. Moreover, some abbreviations are very similar (e.g., PTL,
PTR), which further complicates the text.
4. I would recommend adding version numbers for R packages used in the study.
5. I would recommend systematically using italics for gene names (e.g., KRAS, BRAF) to
separate them from gene products.
Please review this paper.
user
Title: Primary Tumor Resection with or without Metastasectomy for Left- and Right-sided Stage
IV Colorectal Cancer: An Instrumental Variable Analysis
Version: 1 Date: 11 Jan 2022
Reviewer's report:
In this study, Ling Yin et al. have evaluated the associations between primary tumor resection
(with or without metastasectomy) and survival in left- and right-sided stage IV colorectal cancer.
I think the research aim is relevant, and the study design seems appropriate to address that. The
epidemiological/statistical analyses seem suitable for the task, but they are quite complex, and
I think that a separate review by an epidemiologist would be useful. I think the manuscript is
quite well-written. I have just a few minor suggestions to improve the manuscript:
1. I would recommend being more cautious with implying causation (such as page 27, line 21;
"Our instrumental variable analysis shows tat PTR does not improve survival..."), considering
that this retrospective study can only show associations, not causation. Please review the whole
manuscript and reconsider such conclusions.
2.  The word"splenic" is missing from "... left-sided CRC occurs in flexure, ..." (page 5, line 21).
3. Please consider, whether all abbreviations are necessary. In my opinion, the abbreviations
make this text more difficult to read. Moreover, some abbreviations are very similar (e.g., PTL,
PTR), which further complicates the text.
4. I would recommend adding version numbers for R packages used in the study.
5. I would recommend systematically using italics for gene names (e.g., KRAS, BRAF) to
separate them from gene products.
assistant