Kishan AU, et al. - In order to investigate the clinical implications of local failure (LF) after definitive radiotherapy, researchers performed an individual patient-level meta-analysis of six randomized trials. They carried out an individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) in six randomized clinical trials. They utilized multivariable Cox proportional hazard models to assess the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were formed to estimate the effect of specific transitions between disease states on these endpoints. The study found that LF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. It was noted that LF events warrant consideration for intervention, potentially implying a rationale for upfront treatment intensification. Nevertheless, if these findings use to all men or just those without significant comorbidity remains to be ascertained.