AR and Familial prostate cancer: Nevertheless, as PSMA expression is often suppressed in AR-negative advanced prostate cancers and liver metastases, a definition of PSMA positivity is a prerequisite for the use of PSMA-radioligand therapy; in addition, PSMA heterogeneity across tumoral and spatial, inter-patient, intra-patient, lineage, and temporal dimensions presents a challenge for efficient patient management [69,70].