Additionally, PSMA-PET enables therapeutic treatment approaches such as metastasis directed therapy and radioligand therapy. Our review of the current clinical applications of PSMA-PET aims to provide a comprehensive overview for a broad audience by summarising the extensive body of literature. While discussing the strengths of PSMA-PET, we also highlight its limitations, particularly its impact on clinical decision-making and therapeutic strategies.
Compared to conventional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy, PSMA-PET offers superior sensitivity and specificity for the primary staging of intermediate- and high-risk PCa, the diagnosis of biochemical recurrence (BCR) and for metastatic prostate cancer. The ability to detect even small metastatic lesions provides a more precise evaluation of disease burden, even at low PSA levels. Consequently, PSMA-PET has significantly influenced the diagnostic workflows outlined in major clinical guidelines, leading to its broad clinical adoption. In addition to the diagnostic approaches already recommended in guidelines, recent studies investigated the potential use of PSMA-PET imaging at earlier stages, such as in biopsy planning. Furthermore, there are prognostic approaches where the standardized uptake value (a semiquantitative measurement of tracer uptake) is being discussed as a prognostic factor.
Despite its strengths, using PSMA-PET for PCa diagnostics is not without limitations. One major challenge is the phenomenon of stage migration (Will Rogers phenomenon), where more accurate imaging leads to an apparent shift in disease classification, potentially altering treatment decisions without clear evidence of improved long-term outcomes. Furthermore, false positives in PSMA-PET imaging remain a concern, particularly with unspecific bone uptake. Most importantly, most treatment-defining clinical trials for PCa are based on conventional imaging methods and cannot be directly translated to PSMA-based approaches without careful consideration. Prospective data on the impact of PSMA-PET imaging on long-term oncological outcomes are currently lacking.
Beyond diagnostics, PSMA-PET has enabled therapeutic approaches for metastatic prostate cancer, particularly radioligand therapy such as Lutetium therapy. Phase II studies and preliminary results of a phase III study have demonstrated a significant extension of overall survival by offering Lutetium therapy as an addition to standard therapy for metastatic castration resistant PCa.
Moreover, early-phase studies suggest potential applications of PSMA-targeted therapies in hormone-sensitive metastatic PCa and even neoadjuvant settings. Especially for younger generations of urologists, PSMA-PET has become such an integral part of PCa management that PCa workup without it seems inconceivable. However, as PSMA-PET continues to redefine diagnostic and therapeutic strategies, it is critical to recognize that many foundational studies guiding PCa treatment did not incorporate this technology. Consequently, further research is required to evaluate the true clinical impact of improved imaging on therapeutic outcomes. Moving forward, prospective trials incorporating PSMA-PET into clinical decision-making frameworks will be essential to ensure that its widespread adoption translates into meaningful benefits for patients.
Written by: Franz von Stauffenberg,1 Cédric Poyet,2 Stephan Beintner-Skawran,3 Alexander Maurer,3 Florian A. Schmid1
- Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Department of Urology, Stadtspital Triemli, Zurich, Switzerland.
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.