The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer

Abstract

Radiolabelled prostate-specific membrane antigen (PSMA)-based Positron emission tomography-computed tomography (PET-CT) has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, namely Lu-PSMA has been shown to be a potential new line of treatment for metastatic castrate resistant prostate cancer. W hole-body MRI (WB-MRI) has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multi-centre studies comparing 68 Ga-PSMA PET-CT and WB-MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and urinary excretion of tracers confounding image interpretation at the vesicoureteral junction. Additionally , studies have described how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA-positive lesions . Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes it challenging to accurately monitor treatment response to ADT with PSMA-PET. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB-MRI. Emerging data supports the wider adoption of PSMA-PET and WB-MRI for diagnosis, staging, disease burden evaluation and response monitoring, though their relative roles in the standard of care management of patents is yet to be fully defined.. Key points• Next-generation imaging techniques have been found to affect prostate cancer disease state classifications as their increased sensitivity can result in stage migration.

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

“…(Consensus for regular imaging regardless of PSA) So far, no large phase III trials in mCRPC have systematically used next-generation imaging for monitoring. For PSMA PET imaging, response criteria need to be defined because PSMA expression may increase with systemic therapy, in particular when starting ADT and/or ARPI therapy [82][83][84][85]. In 2016, the PCWG3 did not include next-generation imaging as a standard imaging modality for use in clinical trials, primarily due to the lack of criteria to define response/progression on systemic therapies [81].…”

The roles of proteases in prostate cancer

“…Among such proteases, prostatespecific membrane antigen (PSMA) is well established and a prime example of a theranostic approach based on tumor-specific overexpression of a cell-surface proteases. 250,251 PSMA is a cell-surface carboxypeptidase that is strongly expressed by prostate cancer cells, also at metastatic sites. Various specific ligands have been developed to utilize this specific expression profile for radiologic imaging and targeted drug delivery.…”

“…Various specific ligands have been developed to utilize this specific expression profile for radiologic imaging and targeted drug delivery. 250,251 Recently the type II transmembrane protease fibroblast activation protein (FAP) has emerged strongly as a biomarker and putative target for detection and potential treatment of a range of malignancies. 252 In contrast to other proteins that are enriched on malignant cells, FAP is enriched on the surface of fibroblasts in the tumor stroma, the socalled cancer-associated fibroblasts (CAFs).…”

“…Proteases are also useful for cancer imaging and as theranostic targets. Among such proteases, prostate‐specific membrane antigen (PSMA) is well established and a prime example of a theranostic approach based on tumor‐specific overexpression of a cell‐surface proteases 250,251 . PSMA is a cell‐surface carboxypeptidase that is strongly expressed by prostate cancer cells, also at metastatic sites.…”

Progression in immunotherapy for advanced prostate cancer

“…The 5year survival rate for patients with mCRPC is approximately 30% (9). Compared with conventional examinations such as CT and bone scan, the new PSMA-PET/CT and FDG-PET/CT have higher sensitivity for metastases, especially in patients with lower PSA levels (10)(11)(12). The advancement of imaging technology has further increased the number of mCRPC patients.…”