Is it time to redefine the Phoenix criterion for biochemical failure in the era of PSMA PET/CT?

Abstract

319 Background: Biochemical recurrence (BCR) of prostate cancer (PCa) is traditionally defined by the Phoenix criterion (PSA rise ≥ 2 ng/ml above nadir). However, prostate-specific membrane antigen (PSMA) PET/CT can identify recurrent or metastatic disease at much lower PSA levels. This study evaluated the detection rate and clinical relevance of PSMA PET/CT across varying PSA values in patients with PCa following curative-intent radiotherapy (RT). Methods: We retrospectively analysed 182 patients managed between January 2021 and December 2024 who received curative-intent RT for PCa. Clinical data included PSA at the time of imaging, Gleason score, disease distribution, and prior primary treatment. Results: Of 182 patients, 167 (91.7%) underwent PSMA PET/CT; 149 (81.8%) demonstrated PSMA-avid lesions indicating local recurrence and/or metastatic disease, while 18 (9.8%) had negative scans. Thirty patients (17.9%) did not meet the Phoenix criterion (PSA < 2 ng/ml) yet had positive PSMA findings. Of these, 20 (66%) had nodal metastases, 2 (6.6%) had local recurrence with nodal and bone metastases, 3 (10%) had nodal and bone disease, and one patient (3.3%) had local recurrence with visceral and/or bone metastases. No correlation was observed between Gleason score and PSMA positivity in this subgroup (Gleason 7 = 53.3%, Gleason 8 = 26.6%, Gleason 9 = 20%). A further 23 patients (15%) had PSA > 2 but < 3 ng/ml; 14 (60.8%) demonstrated nodal metastases, 7 (30.4%) bone metastases, 4 (17.3%) combined local/nodal/bone disease, and 2 (8.6%) visceral metastases. Most had higher-grade tumours (Gleason 9 in 39%). Eighteen patients (12%) had PSA > 3 but < 4 ng/ml; 6 (33.3%) had nodal metastases, 6 (33.3%) bone metastases, 3 (16.6%) nodal plus bone disease, and 2 (11.1%) visceral metastases. Within this group, 44.4% had Gleason 9 and 38.8% had Gleason 7 disease. Conclusions: PSMA PET/CT demonstrates high sensitivity for detecting recurrent and metastatic PCa even at PSA ≤ 4 ng/ml, identifying disease in over 40% of scanned patients. Detection of nodal and distant metastases below the Phoenix threshold challenges the current reliance on biochemical criteria to trigger imaging. Early PSMA PET/CT may enable prompt therapeutic intervention and improved clinical outcomes. Prospective studies are warranted for validation.