PONE-D-24-05414Comparative Analysis of Novel Hormonal Agents in Non-Metastatic Castration-Resistant Prostate Cancer: A Taiwanese PerspectivePLOS ONE

Dear Dr. Lin,

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Wen-Wei Sung, M.D., Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: 1. Unmet Need Highlight:

o In the background section, the authors should address the unmet need more explicitly. Specifically, they could emphasize the lack of direct head-to-head comparisons among the three FDA-approved ARPis (darolutamide, apalutamide, and enzalutamide). Highlighting this gap would strengthen the rationale for their study.

2. Clarification on State Description:

o In line 21-22, the sentence mentions: “Non-metastatic castration-resistant prostate cancer (nmCRPC) refers to this state, which presents a potential threat to life.” However, the specific state is not clearly described. Please rephrase this sentence to provide clarity.

3. Support for Chemotherapy Use:

o Line 35-36 states: “Furthermore, when compared to chemotherapy, these treatments have demonstrated effectiveness in averting severe adverse effects [2, 7].” It’s essential to verify whether the cited references or guidelines indeed support the use of chemotherapy in nmCRPC status. I recommend asking the authors to reiterate this statement with appropriate evidence.

4. Replace “Review” with “Study”:

o In line 67, consider replacing “review” with “study” to avoid any confusion. This change will prevent readers from mistaking the article as a review article.

5. Clarification on nmCRPC Definition:

o Lines 104-107 discuss nmCRPC status. However, the usual definition excludes previously identified radiologically evident metastasis. The statements in this section seem to deviate from the standard definition. Please ask the authors to clarify this point for better alignment.

Reviewer #2: The manuscript examines the efficacy and safety of three novel hormonal agents (NHAs) – apalutamide, darolutamide, and enzalutamide. Data were gathered from two leading prostate care centers in Taichung, Taiwan. Patient characteristics, treatment specifics, PSA responses, and adverse events were meticulously analyzed. A total of 64 patients participated in this study, comprising 29 darolutamide, 26 apalutamide, and 9 enzalutamide patients. While baseline characteristics varied among the three patient cohorts, treatment responses yielded similar outcomes. The apalutamide group exhibited a higher incidence of adverse events, notably skin rash. Discontinuation rates due to adverse events varied among the groups, with patients receiving darolutamide displaying a lower likelihood of treatment discontinuation. These findings indicate the need to make individual therapy and optimize treatment plans for diverse patients.

Comments:

1. Think about demonstrating the PSA or other character changes across various treatments for greater clarity with figures.

2. Strengthen your conclusion by validating it with additional datasets.

3. Please carefully review and correct any typos and grammar errors.

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Reviewer #1: Yes: Tzu-Ping Lin

Reviewer #2: No

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Comparative Analysis of Novel Hormonal Agents in Non-Metastatic Castration-Resistant Prostate Cancer: A Taiwanese Perspective

PONE-D-24-05414R1

Dear Dr. Lin,

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.

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Kind regards,

Wen-Wei Sung, M.D., Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments: