PET/CT Imaging of Prostate Cancer in the Era of Small Molecule Prostate Specific Membrane Antigen Targeted Tracers

Prostate cancer (PCa) is the most common type of cancer in men and the third leading cause of cancer death worldwide. Staging and restaging of PCa are crucial for treatment planning and prognosis as the accurate localization is of high relevance for tailor-made salvage therapy (e.g. salvage radiotherapy or salvage lymph node dissection) and early detection of unknown metastatic spread can provide a survival benefit.

Various studies have shown that the standard of care (i.e. that which has been used up to now) for PCa suffers from various limitations. Computed tomography (CT) and magnetic resonance imaging (MRI) relies primarily on size for the detection of lymphogenous spread. However, up to 80% of nodal metastases in PCa are smaller than 8 mm in size, and thus morphological imaging fails to recognize most of them. Furthermore, the additional information gained from diffusion-weighted images (DWI) on MRI in many cases fails to distinguish between benign and malignant lymph nodes. Thus, when using anatomical imaging a high number of false-negative results are generated, especially when it comes to nodal staging in intermediate-to-high risk or metastatic PCa.

Besides that, high false-positive results are produced due to enlarged lymph nodes representing other pathologies (reactive, granulomatous disease, nodal metastases from a synchronous primary). Bone scintigraphy, which detects the increased osteoblastic activity earlier than CT, is also hampered by a high number of false-positive findings. Similarly, visceral findings detected with conventional imaging have a range of differential diagnoses and do not offer the specificity provided by molecular imaging, which targets the tumor cells directly.

Consequently, a lot of effort has been carried out in recent years in developing new molecular imaging techniques in tackling these problems, with small-molecule prostate-specific membrane antigen targeted (PSMA) tracers being the most promising agents. It has been recently proven that PSMA PET/CT can replace CT and bone scintigraphy (combined) in the staging of advanced prostate cancer. Furthermore, the examination gained general acceptance through its excellent performance in biochemical recurrence, both for castration-naïve and castration-resistant tumors, and should be implemented where available. It is undisputed that PSMA PET/CT provides a more accurate picture of prostate cancer patients and can lead to both upstaging and downstaging, thus affecting therapeutic management and appears as the next imaging standard for prostate cancer for the years to come. In addition, these molecules can be labeled in many cases with a therapeutic counterpart (of the diagnostical radiopharmaceutical) using alpha or betta emitters for therapeutic purposes (i.e. theranostics).

Written by: Alexis Vrachimis, MD, PhD, Director of Nuclear Medicine, German Oncology Center, Agios Athanasios, Cyprus

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