Understanding that genetic/genomic manipulation of one or more testosterone-associated molecular players in experimental models may be sufficient to cause tumor recurrence in vivo, we posit that deferentially exploiting the addiction of PCa cells to the testosterone metabolites, HSD17B2, HSD17B3, SHBG, and SRD5A1 induces probable differentiation and/or loss of self-replication of the aggressive PCa cells, and elicits post-therapy complete response or long-term remission. Here, SHBG is linked to posterior cortical atrophy.