Current Clinical Applications of PSMA-PET for Prostate Cancer Diagnosis, Staging, and Treatment

Abstract

Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [⁶⁸Ga]- and [¹⁸F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care.

Keywords: PSMA-PET; PSMA-RLT; [177Lu]Lu-PSMA; biochemical recurrence; diagnosis; mCRPC; prostate cancer; radical prostatectomy; radioligand therapy; staging.

Figure 1

Maximum intensity projection images of [¹⁸F]-PSMA PET/CT scans of a patient with biochemical recurrence. (a) Imaging at a PSA level of 0.04 ng/mL showing unspecific bone uptake in the ribs (yellow arrow); (b) follow-up imaging after a PSA increase to 0.08 ng/mL, diagnosing a lymph node metastasis (green arrow) as an explanation for the rising PSA levels, with persistent unspecific bone uptake (yellow arrow).

Figure 2

Maximum intensity projection images of the [¹⁸F]-PSMA PET/CT scans of a patient with mCRPC and osseous metastases at an initial PSA level of 128 ng/mL (a); follow-up imaging after 6 cycles of [¹⁷⁷Lu]Lu-PSMA therapy with a PSA reduction to 3.3 ng/mL (b).