Although it seems almost unquestionable that loss of TP53 and RB1 is necessary for NE/SC, next-generation sequencing data of matched DNA and RNA show that a substantial fraction (35%) of CRPC with combined biallelic loss of TP53 and RB1 was classified as AR-positive adenocarcinomas without neuroendocrine features [53]. This evidence concerns the gene RB1 and adenocarcinoma.