PONE-D-19-31837

Regional treatments for colorectal cancer metastases in older patients: A systematic review and meta-analysis

PLOS ONE

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http://doi.org/10.1001/jamasurg.2016.5665

http://dx.doi.org/10.3748/wjg.v21.i39.11185

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: In this manuscript the authors focus on an interesting clinical question concerning the management of elder patients affected by CRLM. The article is well written, the PRISMA guidelines are well followed, the statistics are good and the conclusions are fairly supported by the results. I have some minor comments that should be addressed by the authors.

1) I feel that there is some discrepancy and confusion with terminology throughout the manuscript: with "regional treatments" i was expecting only non-surgical treatments while you include also liver resections. I would clearly separate the two and be more appealing even in your title as it is my opinion that you are giving us some sound conclusions that liver resections are a good options in older patients. This is the main message of you article rather than regional and non-surgical treatments.

2) There are too many tables and these are over written. It is good to me because i had the chance to see that you carefully screened the manuscripts. However, this is too much even in the setting of editorial policies i guess. I would merge some tables and cut down the number of words in each field. Give results, not comments.

3) Similarly, the number of figures is way too much. Figure 2,3,4, and 5 for example, i would combine and give one figure with the Forest plots of intraoperative outcomes and one with the postoperative outcomes. We don't need specific results for bile leak and ascites.

Reviewer #2: Authors correctly stated that the treatment of older patients is a hot topic in all the fields of medicine. The treatment of liver metastases from colorectal cancer fell in this topic.

A great effort has been made by them in the evaluation of paper dealing with this argument and published in the English written literature. A total of 29 paper has been selected and evaluated with a rigorous methodology. The paper support the performance of curative treatments even in the setting of older patients, since the results published in the literature and analyzed in this meta-analysis do not show inferior results when compared with those achieved in younger patients.

Included studies are retrospective.

It is obvious that older patients are more prone to develop postoperative complications and this came out also from their analysis.

Few considerations should be evaluated and possibly included in the text.

1) There is no mention of the stage of the diseases that has been treated. It is possible that older patients have been treated for less invasive in term of number of metastatic nodules and diameter of the tumor. At page 8 (Data extraction and quality assessment) there is no mention of the stage of the disease that have been operated. Probably this could not be retrieved from papers. Nevertheless, I believe it should be mention as not retrievable and included in the discussion chapter.

2) At page 8 it is stated that the “type of intervention” has been included into the considered variable. When dealing with surgical treatments, “type of intervention” usually refers to the extension of the hepatectomy performed. Maybe the Authors should better clarify the definition.

3) Could it be possible to retrieve the extension of the hepatectomy performed from the collected manuscripts? It is possible that major hepatectomies are rarely permed in older patients. If this data could not be collected, it should be stated in the “data extraction” subchapter and commented in the “Discussion” chapter.

4) Page 50 – Key-point #3. Up to today, the only “curative-intent” strategy in the treatment of colorectal liver metastasis is the surgical resection. It should be stated clearly at this point, not to leading to misunderstandable messages to the readers.

5) As a consequence, it is advisable to include among the key-points, that these patients should be evaluated for treatment by a multidisciplinary committee that should mandatory include the figure of a hepatic surgeon.

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Reviewer #1: No

Reviewer #2: Yes: Gian Luca Grazi, MD

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Surgical and regional treatments for colorectal cancer metastases in older patients: A systematic review and meta-analysis

PONE-D-19-31837R1

Dear Dr. de'Angelis,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Giuseppe Nigri

Academic Editor

PLOS ONE