The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer

Abstract

The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA's expression and its impact on personalised treatment, particularly the use of [¹⁷⁷Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.

Keywords: PSMA PET/CT; aggressive prostate cancer; biochemical recurrence; prostate-specific membrane antigen; uro-oncology.

Figure 1

Clinical case from routine practice at the Peter MacCallum Cancer Centre (PMCC), where the use of PSMA PET/CT had dramatically changed therapeutic interventions. The patient presented with a PSA of 45 and a left Prostate Imaging Reporting and Data System (PIRADS) 5 lesion on MRI, with the biopsy confirming left GGG2 disease. The MRI and CT scans also showed a suspicious sclerotic lesion in the left iliac crest, which was concerning for bony metastases (A,B). The red arrow highlights the bony lesion in the left iliac crest. The bone appeared to show no apparent disease. Conversely, the PSMA PET/CT showed high PSMA avidity, with a maximum SUV (SUVMax) of 21.9 in the left prostate lesion and no avidity within the previously identified bone lesion (C,D). The patient proceeded to have a radical prostatectomy (RP) for localised high-risk PCa (E). At 3 years after the curative treatment, the patient’s PSA remained undetectable.

Figure 2

PSMA immunohistochemistry (magnification 20×). (A) Cytoplasmatic immunoreaction; (B) membranous positivity. Visual scores for PSMA positivity: (C) score 0, (D) score 1+, (E) score 2+, and (F) score 3+ (both cytoplasmic and membranous positivity) [20]. Reused under open access Creative Commons CC BY 4.0 license.

Figure 3

PMCC patient with mCRPC. (A) [⁶⁸Ga] Ga-PSMA-11 PSMA PET/CT in a patient after six lines of prior therapy. (B) After 8 GBq of [¹⁷⁷Lu]Lu-PSMA-617: quantitative SPECT/CT demonstrating the delivery of 68 Gy to adrenal metastases, 33 Gy to bone metastases, and <4 Gy to off-target organs (parotid/kidneys). (C) Three months after two cycles of [¹⁷⁷Lu]Lu-PSMA-617: repeat PSMA PET/CT demonstrated a complete response. (D) CT also demonstrated a marked response with a reduction in the size of the right adrenal metastasis and resolution of the left adrenal and pulmonary metastases.