Metastasis-free survival as a new endpoint in castration- -resistant prostate cancer

Recent breakthrough recognition of metastasis-free survival as a clinically relevant endpoint has opened a new era in the management of advanced prostate cancer. The need for new, intermediate endpoints is the logical consequence of scientific advances in prostate carcinoma. The treatment algorithms for non-metastatic castration-resistant prostate cancer (M0 CRPC) have recently been updated by adding novel anti-androgen apalutamide, and also enzalutamide for high-risk patients.

To review clinical evidence of metastasis-free survival as an efficacy endpoint used in prostate cancer studies, especially those in an advanced stage of the disease and identify its clinical benefit and correlation with overall survival.

Literature search up to October 2019  was conducted, including clinical trials and clinical practice guidelines.

Metastasis-free survival (MFS) was used as the primary endpoint in the registration of clinical trials of second-generation anti-androgens. The study results have demonstrated the beneficial effect of these anti-androgens on delaying the development of metastases or death (MFS), with median MFSextended by 22‒24 months. The correlation tests have shown a positive correlation of MFS and overall survival.

The metastasis-free survival can be considered a clinically significant and reliable efficacy endpoint in both localized prostate cancer patients and M0 CRPC patients being at high-risk of disease progression (Ref. 15).