In conclusion, in metastatic PC patients, selected primary tumor characteristics such as high tumor cell proliferation (Ki67 index) in combination with low PSA expression, and a reactive stroma response with loss of AR+ stromal cells and increased stromal cell proliferation, can predict the development of metastases of a particularly aggressive subtype in high need of complementary treatment to standard ADT. This evidence concerns the gene MKI67 and pachyonychia congenita.