¹⁷⁷Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Round 1

Reviewer 1 Report

This systematic review and meta-analysis analyses Lu-PSMA radioligand therapy in the "third-line" setting by comparing RCT data of various options including cabazitaxel and Lu-PSMA. This builds on a previous analysis performed by the group which is widely cited. The work is timely in view of recent publication of VISION and TheraP trials. PRISMA-NMA guidelines were followed. Outcomes measured include PSA decline > 50%, progression-free survival, overall survival, anaemia, leukopenia and thrombocytopenia. A limitation is that individual data from the trials was not utilised for this analysis; this is correctly stated in the manuscript. I cannot comment on the accuracy of the statistical analysis as I have not tried to replicate results. By incorporating, the results of two major randomised trials published this year, the data provides additional value to the existing literature. I have no major comments. 

Author Response

thank you

Reviewer 2 Report

The aim of the present systematic review and network meta-analysis is to evaluate randomized controlled trials of third-line treatments of patients with metastatic castration-resistant prostate cancer (mCRPC) in order to assess the clinical benefits and harms of the treatments. The authors analyzed seven randomized controlled trials, including 3.960 patients, and eight treatments. Obtained results showed that PRLT is the third-line treatment with the highest effectivity and safety.

The paper is very well written, and I think that the topic of the study could be of high interest for the readers of Biomedicines. The methodology is sound and obtained results are correctly discussed.  

No major concerns from my side.

I just propose a few minor suggestions about parts of the manuscript whose revision might potentially improve the reported data's understanding and readability.

1) “Metastatic castration-resistant prostate cancer was defined by the standard definition”. Please provide a reference.

2) It is not abundantly clear why the ALSYMPCA trial (radium-223 dichloride) has been excluded from the systematic review. This point should be commented on in the discussion.

3) The authors should provide an additional figure showing the increased OS, using the same template of Figure 2.

Author Response

1.Metastatic castration resistant prostate cancer. Please define and provide a reference. OK.
2.Why was ALSYMPCA trial not included in the NMA? The ALSYMPCA trial examined L1 and L2 treatments with radium.
3.The figures of rPFS and OS should use same template. OK, the revised Figures for rPFS and OS give time measured in years om x axis and have the same color for the same treatment in both figures.