Since RB1, TP53, and PTEN loss are enriched in NEPC but also present in a subset of prostate adenocarcinoma [23], this observation highlights that while RB1 and PTEN loss more frequent in cancer with neuroendocrine differentiation, loss of these tumor suppressors is associated with aggressive mCRPC even in the absence of neuroendocrine differentiation. This evidence concerns the gene RB1 and prostate adenocarcinoma.