Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Here, RB1 is linked to Familial prostate cancer.