Abstract
Background: Non-metastatic castration-refractory prostate cancer (nmCRPC) is defined by increasing serum prostate specific antigen (PSA) levels despite androgen deprivation therapy in the absence of metastases on standard imaging methods including CT of the chest, abdomen and pelvis, and bone scan. Patients with nmCRPC and short PSA doubling time (PSAdt) are at high risk of developing early metastatic disease.
Objectives: The objective of this review is to summarize current data on the treatment of nmCRPC. The current data support the efficacy of three novel androgen receptor targeted agents (ARTA), darolutamide, apalutamide and enzalutamide.
Conclusions: The design and eligibility criteria of the three key studies with darolutamide, apalutamide and enzalutamide were similar. Patients were required to have a PSAdt < 10 months.
The study allowed the participation of patients with local lymphadenopathy (below the aortic bifurcation level) of < 2 cm in the ARAMIS (darolutamide) and SPARTAN (apalutamide) studies and < 1.5 cm in the PROSPER (enzalutamide) study. All of these studies have shown prolongation of metastasis-free survival as well as improved overall survival in the active arms.
Prolonging the time to metastasis in patients with nmCRPC is an important therapeutic objective in itself, as skeletal metastases are associated with disease symptoms, such as bone pain. The evidence of extended survival reinforces the indication of ARTA in nmCRPC therapy.
The early inclusion of ARTA in the treatment algorithms for prostate cancer raises questions about sequencing of subsequent systemic therapies. The use of advanced imaging methods such as PET using a labeled prostate specific membrane antigen ligand is also discussed.
However, according to the current consensus, the findings of distant metastases using these next-generation imaging methods do not change the dia-gnosis of nmCRPC, if no distant lesions are detected by conventional staging.