Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer

Junichi Sakamoto; Heita Ozawa; Hiroki Nakanishi; Shin Fujita

doi:10.1371/journal.pone.0241815

Peer Review History

Original SubmissionJune 29, 2020
29 Jul 2020 Decision Letter - Norikatsu Miyoshi, Editor PONE-D-20-18946 Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer PLOS ONE Dear Dr. Sakamoto, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 12 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This article was described about survival after para-aortic lymph node dissection of the colorectal cancer patients. Given the nature of this relatively small study, caution needs to be exercised to interpret the presented findings. But, the report was well written. Comment In page23, line 49-50, the authors described that patients with PALN metastasis with other organ metastasis should be excluded from indication for PALN dissection. It is misunderstanding by these results that all the patients underwent the surgery in this series. This is not a report of the efficacy of PALN dissection for the patients with pM1b/c compared with those who did not underwent PALND. Certainly, the survival of the patients with pM1a is superior to that of other patients. The PALN dissection is good indicated for the patients with pM1a, from this report. Nevertheless, all recurrence after R0 resection of the patients with pM1b/c occurred distant other organ, which means that the PALND potentially have certain treatment effect of local control in the pM1b/c cohort, especially in the era of chemotherapy matured. The study period was extremely long, including the period of chemotherapy drug lag. From this paper, anyone cannot deny that the combination of intensive and intensified chemotherapy and PALND may be effective for the patients, even if with pM1b/c and PALN metastasis. It is appropriate to use the term “maybe excluded” or “possibly excluded from indication for PALN dissection” It is right to emphasize that “pM1a is good indication” in conclusion. Minor comments # Does the study include both patients who underwent PALN dissection or PA lymphadenectomy? # In page18, line2-5, the authors said that there were no statistically significant differences in clinico-pathological characteristics between patients with pM1a and pM1b and pM1c. The rate of adjuvant treatment is different between two groups. Reviewer #2: In this study, authors evaluated the oncologic outcomes after synchronous resection of PALN metastasis in left-sided colon and rectal cancer as a retrospective study. The 3- year RFS rate was significantly better in the pM1a group than in the pM1b/pM1c group, and they concluded PALN dissection for left-sided colon or rectal cancer with synchronous PALN metastasis can be a feasible treatment. The aim of this study and their opinion are understandable. However, there are some points to be revised. They selected patients with curative surgery. There were 7 M1b patients and 3 M1c patients.　 Please describe the details of these metastases and the surgery (simultaneous surgery or irregular surgery). Also, please indicate from which point you started calculating RFS and OS. They said that patients with PALN metastasis with other organ metastases should be excluded from the indication for PALN dissection in discussion section. Patients with M1b/M1c had a poor prognosis and may not need PALN resection. However, regarding whether PALN dissection is effective in patients with M1a, it is necessary to compare the prognosis of patients with and without PALN dissection. Is this comparison possible with your dataset? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. 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Revision 1
11 Sep 2020 Author Response August 9, 2020 Norikatsu Miyoshi, M.D., Ph.D., FACS Academic Editor PLOS ONE Re: Manuscript ID:PONE-D-20-18946 Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer Dear Dr. Norikatsu Miyoshi: Thank you for the thoughtful and constructive feedback you provided regarding our manuscript (PONE-D-20-18946), titled “Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer.” We also appreciate the time and effort you and each of the reviewers have dedicated to providing insightful feedback on ways to strengthen our paper. Thus, it is with great pleasure that we resubmit our article for further consideration. We have incorporated changes that reflect the detailed suggestions you have graciously provided. We also trusted that our edits and the responses we provided below satisfactorily address all the issues and concerns you and the reviewers have noted. To facilitate your review of our revisions, the following is a point-by-point response to the questions and comments delivered in your letter. Reviewer #1 This article was described about survival after para-aortic lymph node dissection of the colorectal cancer patients. Given the nature of this relatively small study, caution needs to be exercised to interpret the presented findings. But, the report was well written. (Response) We thank you for providing constructive comments regarding the improvement of the original manuscript. (Comment 1) In page23, line 49-50, the authors described that patients with PALN metastasis with other organ metastasis should be excluded from indication for PALN dissection. It is misunderstanding by these results that all the patients underwent the surgery in this series. This is not a report of the efficacy of PALN dissection for the patients with pM1b/c compared with those who did not underwent PALND. Certainly, the survival of the patients with pM1a is superior to that of other patients. The PALN dissection is good indicated for the patients with pM1a, from this report. Nevertheless, all recurrence after R0 resection of the patients with pM1b/c occurred distant other organ, which means that the PALND potentially have certain treatment effect of local control in the pM1b/c cohort, especially in the era of chemotherapy matured. The study period was extremely long, including the period of chemotherapy drug lag. From this paper, anyone cannot deny that the combination of intensive and intensified chemotherapy and PALND may be effective for the patients, even if with pM1b/c and PALN metastasis. It is appropriate to use the term “maybe excluded” or “possibly excluded from indication for PALN dissection”. It is right to emphasize that “pM1a is good indication” in conclusion. (Response) We appreciate the Reviewer’s comment on this point. The current study did not include the patients without PALN dissection. It is inappropriate to use the term “should be excluded”. Accordingly, we have changed the following text in the Discussion (page21, lines 50-51): “Consequently, patients with PALN metastasis with other organ metastases should be excluded from the indication for PALN dissection.” to “Consequently, patients with PALN metastasis with other organ metastases were possibly excluded from the indication for PALN dissection.” Moreover, we have changed the next text in the Abstract (page8, lines19-21) and Conclusion (page23, lines98-100): “PALN dissection for patients without other organ metastases in left-sided colon or rectal cancer can be a feasible treatment option as it is for liver and lung metastasis.” to “PALN dissection for patients without other organ metastases in left-sided colon or rectal cancer is a good indication as it is for liver and lung metastasis.” (Comment 2) Does the study include both patients who underwent PALN dissection or PA lymphadenectomy? (Response) As the Reviewer noted, our original expression here may be a bit misleading. In this study, we excluded patients who underwent non-systematical PALN dissection. Accordingly, we have added the following text in Materials and methods (page11, lines 22-23): “In the present study, we excluded patients who underwent PA lymphadenectomy.” (Comment 3) In page18, line2-5, the authors said that there were no statistically significant differences in clinico-pathological characteristics between patients with pM1a and pM1b and pM1c. The rate of adjuvant treatment is different between two groups. (Response) The reviewer’s comment is correct. To clarify, we have revised as “There were no statistically significant differences in clinicopathological characteristics between patients with pM1a and pM1b and pM1c besides the rate of adjuvant treatment.” (page17, lines2-5) Reviewer #2 (Response) We wish to express our appreciation to the Reviewer for his or her insightful comments, which have helped us significantly improve the paper. (Comment 1) In this study, authors evaluated the oncologic outcomes after synchronous resection of PALN metastasis in left-sided colon and rectal cancer as a retrospective study. The 3- year RFS rate was significantly better in thepM1a group than in the pM1b/pM1c group, and they concluded PALN dissection for left-sided colon or rectal cancer with synchronous PALN metastasis can be a feasible treatment. The aim of this study and their opinion are understandable. However, there are some points to be revised. They selected patients with curative surgery. There were 7 M1b patients and 3 M1c patients.　 Please describe the details of these metastases and the surgery (simultaneous surgery or irregular surgery). Also, please indicate from which point you started calculating RFS and OS. They said that patients with PALN metastasis with other organ metastases should be excluded from the indication for PALN dissection in discussion section. Patients with M1b/M1c had a poor prognosis and may not need PALN resection. However, regarding whether PALN dissection is effective in patients with M1a, it is necessary to compare the prognosis of patients with and without PALN dissection. Is this comparison possible with your dataset? (Response)　In the present study, the site of other organ metastases were the liver metastases in 7 patients (pM1b group), and the liver and peritoneal metastases in 3 patients (pM1c group). All patients received simultaneous resection with their primary cancer. Accordingly, we have revised the Table 1 as follows (page14): Moreover, we have added the following text to the Results (page13, lines22-23): “All patients received simultaneous resection of their distant metastases.” Further, as the Reviewer noted, this is not a report of the efficacy of PALN dissection for the patients with pM1a compared with those who did not undergo PALN dissection. This comparison is impossible with our dataset. We have therefore changed and added the following text as one of the limitations of the study (page23, lines88-95): “Finally, the present study did not include the patients without PALN dissection. Consequently, the efficacy of PALN dissection cannot be predicted with total accuracy based on our results. Larger multi-institutional prospective studies are required to overcome the shortcomings of this research. However, our results clearly showed that a favorable prognosis could be expected in selecting patients with left-sided colon and rectal cancers using isolated PALN dissection.” Finally, we have changed the next text in the Abstract (page8, lines19-21) and Conclusion (page23, lines98-100): “PALN dissection for patients without other organ metastases in left-sided colon or rectal cancer can be a feasible treatment option as it is for liver and lung metastasis.” to “PALN dissection for patients without other organ metastases in left-sided colon or rectal cancer is a good indication as it is for liver and lung metastasis.” With these changes to our manuscript, we hereby resubmit our manuscript for a secondary evaluation. Again, thank you for allowing us to strengthen our manuscript with your valuable comments and queries. We have worked hard to incorporate your feedback and hope that these revisions persuade you to accept our submission. Sincerely, Junichi Sakamoto, MD Department of Colorectal Surgery Tochigi Cancer Center 4 Chome-9-13 Yonan, Utsunomiya, Tochigi 320-0834, Japan Tel: 028-658-5151 Fax: 028-658-5669 Email: jsakamoto@tochigi-cc.jp Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0241815.r002
21 Oct 2020 Decision Letter - Norikatsu Miyoshi, Editor Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer PONE-D-20-18946R1 Dear Dr. Sakamoto, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript was well revised about the part I have pointed out. (Comment 3) In page18, line2-5, the authors said that there were no statistically significant differences in clinico-pathological characteristics between patients with pM1a and pM1b and pM1c. The rate of adjuvant treatment is different between two groups. (Response) The reviewer’s comment is correct. To clarify, we have revised as “There were no statistically significant differences in clinicopathological characteristics between patients with pM1a and pM1b and pM1c besides the rate of adjuvant treatment.” (page17, lines2-5) → It doesn’t make sense that “besides the rate of adjuvant treatment”. “except for the rate of adjuvant treatment” or “apart from the rate of adjuvant treatment” would be better. Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No https://doi.org/10.1371/journal.pone.0241815.r003
Formally Accepted
4 Nov 2020 Acceptance Letter - Norikatsu Miyoshi, Editor PONE-D-20-18946R1 Oncologic outcomes after resection of para-aortic lymph node metastasis in left-sided colon and rectal cancer Dear Dr. Sakamoto: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Norikatsu Miyoshi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0241815.r004

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