PONE-D-23-44163The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysisPLOS ONE

Dear Dr. Urabe,

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.

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Reviewer 1.Management of metastatic hormone/castration sensitive prostate cancer has evolved over the last decade. A series of randomized clinical trials have shown that the addition of systemic chemotherapy (docetaxel) and androgen-receptor signaling pathway inhibitors to androgen deprivation therapy (ADT) improvement in cancer related outcomes.

Definitive local therapy is often incorporated in the management. Relief of symptoms or prevention of symptoms, elimination of tumor promoting effects and development of new metastases are cited as justifications for definitive local therapy. However, robust data from randomized clinical trials evaluating the effect of local therapy on improvement in cancer related outcomes have not been reported.

Yamada and coauthors are to be commended for submitting this manuscript which seeks to address this unmet need. The authors report the specifics of the literature search, data extraction and selection of clinical of 11 clinical trials (three randomized control trials and non-randomized trials).

In the 3 randomized clinical trials, with the STAMPEDE trial reported by Parker et al in the Lancet being the largest with nearly 2000 subjects, in unselected subjects local therapy (radiation) did not reveal improvement in biochemical failure-free or overall survival. Pooled results of the non-randomized trials did reveal improvement in progression-free survival, cancer specific and overall survival. Subset analysis showed that the benefit/improvement in cancer related outcomes were noted only in subjects with low tumor burden. This is undoubtedly due the fact that the extent of tumor burden will influence cancer related outcomes. Nevertheless, the results will be helpful to clinicians in identifying patients who are likely to benefit from definitive local therapy. The paper meets an unmet need.

The data presented stand on their merit. However, since English is unlikely the primary language of the authors recommend professional copyediting.Reviewer 2.This study evaluated the prognostic impact of "localized treatment to the primary lesion (LT) plus hormone therapy (HT)" versus "HT alone" in metastatic hormone-sensitive prostate cancer. The analysis is well-conducted, presenting robust evidence supporting the combined treatment approach, particularly in patients with a low tumor burden. However, the conclusion section only mentions "LT," which does not align with the central findings that emphasize the benefits of combining LT with HT. The authors should revise the conclusion to clearly state that the combination of LT+HT contributes to improved prognoses.

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Academic Editor

PLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Management of metastatic hormone/castration sensitive prostate cancer has evolved over the last decade. A series of randomized clinical trials have shown that the addition of systemic chemotherapy (docetaxel) and androgen-receptor signaling pathway inhibitors to androgen deprivation therapy (ADT) improvement in cancer related outcomes.

Definitive local therapy is often incorporated in the management. Relief of symptoms or prevention of symptoms, elimination of tumor promoting effects and development of new metastases are cited as justifications for definitive local therapy. However, robust data from randomized clinical trials evaluating the effect of local therapy on improvement in cancer related outcomes have not been reported.

Yamada and coauthors are to be commended for submitting this manuscript which seeks to address this unmet need. The authors report the specifics of the literature search, data extraction and selection of clinical of 11 clinical trials (three randomized control trials and non-randomized trials).

In the 3 randomized clinical trials, with the STAMPEDE trial reported by Parker et al in the Lancet being the largest with nearly 2000 subjects, in unselected subjects local therapy (radiation) did not reveal improvement in biochemical failure-free or overall survival. Pooled results of the non-randomized trials did reveal improvement in progression-free survival, cancer specific and overall survival. Subset analysis showed that the benefit/improvement in cancer related outcomes were noted only in subjects with low tumor burden. This is undoubtedly due the fact that the extent of tumor burden will influence cancer related outcomes. Nevertheless, the results will be helpful to clinicians in identifying patients who are likely to benefit from definitive local therapy. The paper meets an unmet need.

The data presented stand on their merit. However, since English is unlikely the primary language of the authors recommend professional copyediting.

Reviewer #2: This study evaluated the prognostic impact of "localized treatment to the primary lesion (LT) plus hormone therapy (HT)" versus "HT alone" in metastatic hormone-sensitive prostate cancer. The analysis is well-conducted, presenting robust evidence supporting the combined treatment approach, particularly in patients with a low tumor burden. However, the conclusion section only mentions "LT," which does not align with the central findings that emphasize the benefits of combining LT with HT. The authors should revise the conclusion to clearly state that the combination of LT+HT contributes to improved prognoses.

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Reviewer #1: No

Reviewer #2: No

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The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis

PONE-D-23-44163R1

Dear Dr. Fumihiko Urabe,

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,

Mohamad Abou Chakra

Academic Editor

PLOS ONE

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