Because the non-luminal subtypes C and D are featured by advanced T/N stage, high Gleason score, PTEN and TP53 alterations, they fit into the criteria of Aggressive Variant PCa (AVPC), which defined clinically by rapid progression after androgen deprivation, low PSA level relative to tumor burden, visceral metastasis, neuroendocrine markers or histology, and molecularly by two or more alterations of PTEN, TP53 and RB1 (AVPC molecular signature, AVPC-ms) [25]. The gene discussed is KLK3; the disease is neoplasm.