Non-metastatic castration resistant prostate cancer (nmCRPC) is a clinical setting defined as confirmed rising levels of PSA in patients treated with ADT but without detectable metastases on conventional imaging with computerized tomography (CT) and technetium-99 m scintigraphy. Men with nmCRPC and a PSA doubling time (PSADT) ≤ 10 months are considered at high risk of rapidly developing metastases with a consequent possible impact on survival. Three recent phase III trials have demonstrated, in this setting, the efficacy of adding a next-generation androgen receptor targeted agent (ARTA) to ADT in respect to ADT only, in delaying the development of metastases (metastasis-free survival, MFS) and prolong overall survival. The magnitude of clinical benefit of these agents was even more meaningful if considering the low incidence of drug related adverse events. Our review described the latest advances in the management of nmCRPC, deriving from the pivotal clinical trials, SPARTAN, PROSPER and ARAMIS, in order to support clinicians to optimally manage these patients. Of note, the emergence of novel, more accurate, next-generation imaging techniques (including Ga PSMA-PET/CT), as well as eventual future tumor biomarkers, is modifying the entity and definition of the nmCRPC setting, with a consequent impact on patient's diagnosis and management.
Keywords: Apalutamide; Darolutamide; Enzalutamide; Nonmetastatic prostate cancer; Prostate carcinoma; nmCRPC.
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