Kishan AU, Chu FI, King CR, et al. - Researchers conducted a meta-analysis of six randomized trials to analyze the clinical implications of local failure (LF) after definitive radiotherapy. They included a total of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) in six randomized clinical trials. They used multivariable Cox proportional hazard models to examine the association between overall survival, PCa-specific survival, and distant metastasis free survival and LF as a time-dependent covariate. They further utilized Markov proportional hazard models to analyze the effect of specific transitions between disease states on these endpoints. They found that after receiving upfront radiation therapy, men who experience a local recurrence of high-grade prostate cancer are at significantly increased risks of growing metastases and dying of prostate cancer.