Clinical Trial Protocol for the Apa/Enza-short Study: A Randomized Nationwide Study of Shortened 12-Month Duration of Androgen Receptor Signaling Agent in Combination With Androgen Deprivation Therapy in Patients With Metastatic Low-volume Castration-sensitive Prostate Cancer.

Continuous treatment with an androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) in low-volume metastatic castration-sensitive prostate cancer (mCSPC) may lead to overtreatment, resulting in increased toxicity and higher costs. Evidence to guide a shorter duration of ARPI therapy is currently lacking. The Apa/Enza-short trial evaluates whether a 12-mo course of apalutamide or enzalutamide is noninferior to continuous treatment in low-volume mCSPC. This randomized, open-label, noninferiority study enrolls 400 patients across Dutch hospitals. After 12 mo of ADT + ARPI, eligible patients are randomized to continue or discontinue ARPI treatment, with reinitiation permitted upon prostate-specific antigen (PSA) increase. The primary end point is clinical progression-free survival (cPFS). If noninferiority is demonstrated, this strategy could maintain efficacy while reducing treatment-related toxicity and health care costs.