PRIMORDIUM Study Design^1-3

Abbreviations: ⁹⁹mTc, technetium-99m; ADT, androgen deprivation therapy; APA, apalutamide; AR, androgen receptor; BCR, biochemical recurrence; BICR, blinded independent central review; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; LHRHa, luteinizing hormone-releasing hormone agonist; LND, lymph node dissection; MRI, magnetic resonance imaging; NECP, neuroendocrine carcinoma of the prostate; OS, overall survival; PCa, prostate cancer; PET, positron emission tomography; PO, orally; ppMPFS, PSMA-PET metastatic progression-free survival; PRO, patient-reported outcomes; PSA, prostate-specific antigen; PSADT, PSA doubling time; PSMA, prostate-specific membrane antigen; QD, once daily; R, randomization; RP, radical prostatectomy; RT, radiotherapy; SBRT, stereotactic body radiotherapy; SCCP, small cell carcinoma of prostate; SOC, standard-of-care; T, testosterone.
^aWithin 12 months after RP and without any PSA levels of ≥0.1 ng/mL within the 4- to 8-week period after RP.
^bPSA levels of ≥0.1 ng/mL within the 4- to 8-week period after RP, confirmed by additional measurement at least 3 weeks later.
^cDefined as pathological Gleason score ≥8 or PSADT ≤12 months.
^dAt sites where it is a standard approach, SBRT may be used for ≤3 PSMA-avid distant metastases; the decision to use SBRT must be made before randomization.
^ePSMA-PET-negative (no locoregional and no distant lesions) or PSMA-PET-positive (≥1 locoregional [pelvic] lesion with or without distant [extra pelvic] lesion[s]).
^fPSA will be measured every 3 months until the primary endpoint. If the PSA level remains <0.2 ng/mL, PSMA-PET is assessed by BICR at 6 and 12 months, then annually until PSMA-PET progression. If the PSA level rises to ≥0.2 ng/mL, PSMA-PET is performed immediately and then every 6 months until PSMA-PET progression. T levels and PROs will additionally be assessed.
^gTo achieve ~192 events.
^hPatients will receive within 4 weeks after randomization.
ⁱData collected during this period in routine clinical practice will include therapies administered as SOC per local practice, clinical evaluations, disease progression assessments, and survival status until closure of the interventional cohort.
^jPost-PSMA-PET-progression assessments will include bone scans, CT/MRIs, and PROs.
^kDefined as the appearance of ≥1 new PSMA-PET-positive distant lesion compared with the previous scan assessed by BICR, or death.