The University of Miami Adapt (UAdapt) Trial

In focal therapy lattice extreme ablative (FTLEAD) RT, the multiparametric-MRI (mpMRI) defined gross tumor volume (GTV) will receive 16-20 Gy in a single fraction of RT to the targeted area which is the tumor within the prostate, with or without uSTADT.

Ultra-Short-Term Androgen Deprivation Therapy (uSTADT) is hormone therapy that includes Relugolix. Patients will receive a loading dose of uSTADT for a total duration 4 weeks (28 days), with oral LHRH antagonist relugolix administered daily starting 2 weeks prior to LEAD RT and continuing until 2 weeks afterwards as per Study Calendar. Patients randomized to uSTADT will receive a loading dose of 360 mg of oral relugolix on Day 14 followed by 120 mg of oral relugolix daily from Day 13 to Day 14. Patients will be instructed to take relugolix orally once daily at approximately the same time each day. Patients may take relugolix with or without food and should swallow tablets whole and not crush or chew tablets.

In Hypofractionated LEAD (HypoLEAD), the multiparametric-MRI (mpMRI) defined GTV will receive 12-16 Gy in a single fraction on the first day of treatment, with or without uSTADT. Four weeks after LEAD RT, patients will begin whole prostate moderately hypoLEAD (67.5 Gy in 25 fractions) with pelvic nodal irradiation and further ADT at the discretion of the treating physician.

Participants will receive ADT as per standard of care (SOC).