Non-metastatic castration-resistant prostate cancer in the epoch of PSMA-ligand PET/CT: twilight?

The introduction of prostate-specific membrane antigen-ligand positron emission tomography/computerised tomography (PSMA-ligand PET/CT) into clinical practice has altered the prevalence of non‑metastatic (by conventional imaging) castration-resistant prostate cancer (nmCRPC). We herewith briefly review the biochemical and imaging parameters in nmCRPC and mainly focus on decoding disease localization using PSMA- ligand PET. The effective restaging with more accurate PSMA PET-based disease identification and characterization potentially signifies the entrance of the nmCRPC stage in the twilight zone. Moreover, it seems plausible that the small fraction of the nmCRPC invisible even on PSMA PET may constitute a latent phase of occult growth of the tumor cells. Supposedly, triggering of PSMA overexpression on the PCa cells under androgen deprivation therapy (ADT) through certain anticancer or other therapies such as protein kinase inhibitors (PKIs), dutasteride, or cholesterol-lowering regimes, might further hasten visualisation of micrometastases on PSMA-ligand PET, eventually transforming the nmCRPC stage into a defined, potentially curable target.