Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial

Round 1

Reviewer 1 Report

Please provide complete demographic details of patient involved in this study such as male female sample size in this study.

 Please explain how it impact on male vs female patient

 Please give exaplain if adverse drug reaction found in the study.

In the text following text in the manuscript “Since the end of the 1990s, dose-response analysis of prostate cancer patients treated both with external beam RT and brachytherapy has led to the assumption that the ?/? ratio of prostate cancer is lower than for most other tumours and approaches a value characteristic to late responding tissues”. Please elaborate dose response analysis please read PMID: 36211148, PMID: 36211148 and cite it for more clarification.

Author Response

Please see the attachment.

Author Response File: Author Response.doc

Reviewer 2 Report

This is an excellent work with short follow up time but completely acceptable for evaluating acute toxicity . Evaluating of long term complications at least 5 years later should be interesting .

Author Response

The manuscript has been extensively edited by a native English speaking colleague.

Thanks

Author Response File: Author Response.doc

Reviewer 3 Report

I congratulate the authors on the extremely ambitious project. 

Prostate Cancer SBRT, confirming a solid radiobiological background, has gradually become a mainstay of treatment in the definitive setting. On the other hand, evidence is lacking in the post-op setting. No increase in short-term toxicity nor significant decline in QoL was observed in the present study. Nonetheless, long-term results as well as larger prospective randomized series are needed to confirm this strategy.

I have few comments (minor revision) to improve the Introduction/Discussion:

-       Introduction:

“Regardless of the two settings (adjuvant or salvage), external beam radiation therapy (RT) for prostate cancer is usually a protracted course, since a total dose of 64 Gy to 72 Gy is needed to be effective [1,2]. At the typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 fractions over the course of 7 weeks to complete, which is very costly and extremely time-consuming...”

It is absolutely necessary within the introduction to state that the post-op setting has been drastically impacted this year by the publication of the final results of the RTOG 0534 by Professor Alan Pollack et al regarding a broader use of the pelvic nodal elective irradiation in this setting given, the potential benefits. Reference recommended:

1)    Pollack, A., Karrison, T. G., Balogh, A. G., Gomella, L. G., Low, D. A., Bruner, D. W., Wefel, J. S., Martin, A. G., Michalski, J. M., Angyalfi, S. J., Lukka, H., Faria, S. L., Rodrigues, G. B., Beauchemin, M. C., Lee, R. J., Seaward, S. A., Allen, A. M., Monitto, D. C., Seiferheld, W., Sartor, O., … Sandler, H. M. (2022). The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet (London, England), 399(10338), 1886–1901. https://doi.org/10.1016/S0140-6736(21)01790-6”

-       Discussion:

“...Besides the aforementioned trial [12], only a metanalysis [19] is available on extreme hypofractionation in the salvage setting, including 11 retrospective series, which showed acceptable rates of acute and late GU and GI toxicity, although in all but two the radiation target was a macroscopic recurrence and not the prostate bed...”

Certainly, treatment tolerance represent a major limitation to the advent of hypofractionation in the post-op setting. However, it is interesting to notice that in terms of hematologic toxicity, namely leukopenia, hypofractionation can represent a better approach compared to conventional fractionation. The authors should discuss and reference the following studies:

2)    Iorio, G. C., Spieler, B. O., Ricardi, U., & Dal Pra, A. (2021). The Impact of Pelvic Nodal Radiotherapy on Hematologic Toxicity: A Systematic Review with Focus on Leukopenia, Lymphopenia and Future Perspectives in Prostate Cancer Treatment. Critical reviews in oncology/hematology, 168, 103497. https://doi.org/10.1016/j.critrevonc.2021.103497.

3)    Sanguineti, G., Giannarelli, D., Petrongari, M. G., Arcangeli, S., Sangiovanni, A., Saracino, B., Farneti, A., Faiella, A., Conte, M., & Arcangeli, G. (2019). Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study. Radiation oncology (London, England), 14(1), 23. https://doi.org/10.1186/s13014-019-1223-2

Author Response

Please see the attachment.

Author Response File: Author Response.doc