Rationale
Preclinical and clinical findings showed that upregulation of the prostate-specific membrane antigen
(PSMA) may be accomplished by short-term application of second-line androgen-receptor pathway
inhibitor (ARPI) such as enzalutamide, apalutamide and darolutamide. This upregulation is also known
as the ‘FLARE phenomenon’. The optimum timeframe for maximal upregulation of the PSMA protein
by ARPIs has yet to be determined and may vary between 9 and 14 days. The hypothesis is that the
‘FLARE phenomenon’ might lead to improved imaging and better staging abilities. This will eventually
lead to improved disease outcomes such as improved progression-free survival and quality of life.

Objective
To prospectively investigate whether the ‘darolutamide FLARE phenomenon’, observed after the
administration of the second line ARPI darolutamide in patients with prostate cancer, results in 1) a
higher number of PSMA expressing prostate cancer deposits (either defined as local residual disease
or metastatic disease) and/or 2) in a higher expression of PSMA in individual lesions (determined by
SUVmax) on PSMA PET/CT.