Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients
Round 1
Reviewer 1 Report
It is very intersting review article and authors covers almost all the positive aspects of blood based biomarker. Moreover I advice the author here to add also the limitation of biomarker. Some questions still needs to address such as what else blood based biomarker are in clinical trial and why they fail the trial and FDA guidelines. For e.g. patients heterogenecity varies so does the identifical is race based or particular targeted population based. Some protein showed very high level of expression in afro-american patients compared to caucasian for e.g. CXCR4 or others, then it wont fit to the criteria of blood based biomkar in general. Author need to address the limitation of the same as I mentioned earlier.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Authors responded to previous concerns appropriately
Author Response
We thank the Reviewer for accepting our replies.
Reviewer 3 Report
Thank you to the authors for addressing my comments.
Author Response
Thank you for the Reviewer to accepting our replies.
Round 2
Reviewer 1 Report
Thanks for addressing my concerns and comments.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Very well written review. Authors focused on the blood-based biomarkers for diagnosis and prognosis of prostate cancer. They especially emphasized on the markers predicting response to radiotherapy and radiotherapy-related late side effects. Lots of research is ongoing in this field and this review paper will be a good reference. I would like to request authors to be consistent with the spelling of certain words like "grey" (or gray) etc.
Reviewer 2 Report
Blood-derived biomarker is a very interesting topic with respect to the prostate cancer diagnosis. In terms of novelty of the topic, related review article has been published in different journals including one in IJMS (MDPI) Int J Mol Sci . 2016 Oct 26;17(11):1784, in PLoS one https://doi.org/10.1371/journal.pone.0045802 and in nature communication Prostate Cancer and Prostatic Diseases volume 20, pages12–19 (2017). Here I feel that this review by author Katalin Balázs will just be a redundancy of information. The author should also read the recent article published by Jeremy Clark´Urine-Based Biomarkers for Prostate Cancer”. I am not undermining their effort but they really have to add new value to the review rather than just repeating the same information. In this review, several pieces of information need to address, such as the limitation of biomarker and its applicability for FDA approval. If you see the article published by Hendriks et al., 2017 the author properly addresses those issues and mention the list of biomarker waiting for FDA approval. During the past 2 years, two biomarkers have been approved by the US FDA. These include pro PSA as part of the Prostate Health Index (phi) by Beckman Coulter, Inc and PCA3 as Progensa by Gen Probe, Inc. Author is just giving a very narrow view to understanding the in-depth knowledge of biomarker in the prostate, for e.g. Serum and urinary biomarkers that may be combined with PSA for enhancing the diagnostic accuracy of prostate cancer detection including high-grade disease. The author should also be aware of the fact that 65%–75% of men with a PSA level in the 3/4–10 μg/L range do not have biopsy-detectable prostate cancer, thus to improve specificity and reduce the number of unnecessary biopsies/repeat biopsies, several additional or adjunct tests have been proposed which include percent free PSA, PHI, 4K score, and PCA3. So for me, this review is in incomplete form and did not contain the actual information. Also considering the fact that prostate cancer heterogeneity poses a significant challenge to develop biomarker research, which is also missing in the review.
Reviewer 3 Report
The review is very broad which leads to it being somewhat unfocused. Many of the biomarkers discussed are in various stages of development, some of them will likely never make it to clinical practice limiting the review's utility
Reviewer 4 Report
This is an interesting and timely review on blood derived biomarkers in prostate cancer. Some suggestions for improvement are given below.
Major points
Section 1, Introduction, while interesting, is overly long. Please focus it more, summarizing the main points about PSA and other tests.
The only table, Table 1, focusses solely on miRNA. The authors should consider adding similar tables for CTCs, EVs and cellular and soluble markers, as these are very useful for the reader.
The Conclusion could be improved by adding some future perspectives and recommendations.
Minor points
The title could be changed to ‘Blood-derived biomarkers of diagnosis, prognosis and therapy response in prostate cancer patients’ to better reflect the text.
Page 1, line 15, change ‘progrediating’ to ‘progressing’??
Page 1, Introduction, change Hungarian statistics to European/Worldwide statistics to make more relevant to readers
Page 2, line 44, change to ‘..enable the identification of those patients…’
Page 5, line 17, change to ‘This schematic summarizes…’
Page 8, line 38, change to ‘…disease and poor prognosis in prostate cancer’
Page 9, line 43, change to ‘…patients benefitting from…’
