PSMA PET/CT for the detection of prostate cancer biochemical recurrence after primary radiation therapy: is it time to review the Phoenix criteria?

Abstract

Biochemical recurrence (BCR) in prostate cancer (PCa) after definitive radiotherapy (RT) is defined by a PSA rise ≥ 2.0 ng/mL (Phoenix criteria, Pc). In clinical settings, PSMA PET/CT has demonstrated the ability to identify recurrent disease in case of PSA values remain below this threshold. This retrospective, multicentre study evaluated PSMA PET/CT in patients with rising PSA below the Phoenix-threshold. We retrospectively analysed PCa patients who underwent PSMA PET/CT for rising PSA below Pc in the period 2020-2023. Patients with prior recurrence treatments were excluded. PSMA PET/CT findings were classified by prostate cancer molecular imaging standardized evaluation (PROMISE) score and stratified by D'Amico risk. Treatment decisions were extracted from clinical records. A non‑parametric statistical analysis was employed (MedCalc® software). Sixty patients were included (median age 79 years, IQR: 75-82). Median PSA value was 1.25 ng/ml (range 0.12-5.02), and median PSA doubling time was 11.8 months (range 0-87.9). The overall PSMA PET/CT detection rate was 71.7% (n = 43/60). Of those with positive scans, 81% (n = 35/43) were oligo‑metastatic and 19% (n = 8/43) were multi‑metastatic. According to the PROMISE score, 10 (23%) patients had only local recurrence, 10 (23%) only pelvic lymph node disease, 10 (23%) only distant metastases, 13 (31%) had local and distant disease (both lymph nodes and bone metastases). By D'Amico risk classification, 83.9% (30/35) of unfavourable intermediate/high‑risk patients had a positive PET, compared with 52.0% (13/25) of low/favourable intermediate‑risk patients (chi squared, p < 0.05). Follow‑up data were available for 54 patients (90%). In 92.6% (n = 50/54), PET findings guided therapy choice: 97% (n = 38/39) of PET‑positive patients received additional treatment (hormonal therapy, RT, or chemotherapy), whereas 80% (n = 12/15) of PET‑negative patients were managed with watchful waiting (chi-square, p < 0.001). PSMA PET/CT detects PCa recurrence in about 72% of patients with PSA rises below Phoenix-threshold. By identifying disease at an earlier stage, many patients may become eligible for salvage or metastasis-directed therapies.