PSMA PET/CT imaging for biochemical recurrence in prostate cancer: can it replace conventional imaging and guide salvage therapy?

Biochemical recurrence (BCR) after primary treatment for prostate cancer presents a significant clinical challenge. Conventional imaging modalities have limited sensitivity for detecting sites of recurrence, particularly at low prostate specific antigen (PSA) levels. Prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has emerged as a promising diagnostic tool that may transform the management paradigm for recurrent prostate cancer. To systematically evaluate the diagnostic performance of PSMA PET/CT in patients with biochemical recurrence of prostate cancer, compare it with conventional imaging modalities, and assess its impact on salvage therapy decisions. A systematic review was conducted following the PRISMA guidelines. PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science were searched for studies published between 2020 and 2025. Studies evaluating PSMA PET/CT in patients with biochemical recurrence after primary treatment were included. The primary outcomes were detection rates stratified by PSA levels, diagnostic accuracy compared to conventional imaging, and the impact on management decisions. PSMA PET/CT demonstrated superior detection rates compared to conventional imaging across all PSA levels, with detection rates ranging from 36.2% to 96.7% for PSA levels below 0.5 ng/mL and above 5 ng/mL, respectively. In patients with negative conventional imaging, PSMA PET/CT identified true positive lesions in 64% of cases (95% CI, 56.7%-71.5%). Among patients with high-risk biochemically recurrent prostate cancer and negative conventional imaging, PSMA PET/CT detected distant metastatic disease (M1) in 46% of patients. Management plans were altered in 54-76% of cases based on PSMA PET/CT findings, with significant implications for salvage therapy targeting. PSMA PET/CT significantly outperforms conventional imaging in detecting sites of recurrence across all PSA levels, with particularly notable advantages at low PSA values. The high detection rates and accuracy of PSMA PET/CT in patients with negative conventional imaging support its role as a replacement for or complement to standard imaging protocols, while acknowledging current limitations in availability, cost, and long-term outcome data. PSMA PET/CT findings frequently alter management decisions, enabling more precise targeting of salvage therapies and potentially improving oncological outcomes.