Comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer (mCRPC) has been linked with histology and clinical outcomes to investigate heterogeneity in the genomic landscape of metastatic prostate cancer. Of the genomic alterations examined, which included alterations in AR, RB1 and TP53, only RB1 alteration was significantly associated with poor survival. Alterations in RB1, AR and TP53 were associated with shorter time on androgen receptor signalling inhibitor treatment. The study identifies molecularly defined groups of patients who might benefit from an aggressive treatment approach. The authors have made the tumour-level and patient-level data available for further research.