EAU PCa 17: The Future of Molecular and Functional Imaging

Vienna, Austria (UroToday.com) Dr. Jochen Walz from Marseille, France provided a comprehensive overview of the future of molecular and functional imaging at the EAU Update on prostate cancer in Vienna, Austria. 

Dr. Walz notes that in 2017 “old” PET-tracers such as FDG and choline provide only limited answers for relevant clinical questions in prostate cancer, including (i) initial lymph node staging (sensitivity ~50%), and (ii) detection rates in early biochemical recurrence (PSA <0.5 ng/mL: 5-8% detection rate). For initial staging of lymph nodes, certainly there is promise of improved staging alternatives when considering PSMA-PET. In a study of 130 patients, performance per patient for detecting lymph node metastasis included 66% sensitivity and 99% specificity [1]. In a recent systematic review and meta-analysis of the current literature for 68Ga-PSMA-PET in recurrent prostate cancer [2], the detection rate at PSA 0.2 ng/mL was ~40%, whereas at PSA 1.5 ng/mL, detection rate was ~80%. 

Novel agents include anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine), which is a synthetic L-leucine analog that is transported into the cell but is not metabolized; fluciclovine targets upregulation of amino acid transporters in tumors. Initial studies in recurrent prostate cancer demonstrate that it may be better than choline-PET: among 596 individuals with recurrent prostate cancer, at a median PSA of 2.0 ng/mL, there was 67.7% positive detection rate [3], leading to FDA and EMA approval. 

Although PSMA and probably FACBC perform better than FDG and choline, Dr. Walz wonders if they provide sufficient performance for all relevant clinical questions in prostate cancer? In his mind, there is still space for improvement in the future, including more sensitive tracers, and the ability to not only assess localization but also for monitoring treatment. One such potential tracer is bombesin, an agonist of gastrin-releasing peptide receptor that stimulates growth of prostate cancer cells. This molecule has high receptor density in invasive prostate cancer cells and initial tests using 18F/68Ga labeled bombesin-antagonists are ongoing. Second, the 2-(3{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-arbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18FDCFPyL) labeled PSMA-selective tracer has the same function as PSMA but has better availability, is easier to handle, has better tumor to background ratio, and improved resolution. 

Since we now have a plethora of mCRPC drugs, Dr. Walz feels that early monitoring of response to treatment with novel agents may assist in determining the appropriate sequence of treatment. Currently, response to treatment is primarily done with PSA, a proxy for tumor volume, as PSA is generally more sensitive than any imaging technology we have today. Molecular imaging may be a possible alternative, allowing for determination of early changes in metabolism as a surrogate for treatment response. Current choline and FDG PET imaging is prone to false positives and generally suboptimal for assessing response to treatment. PSMA may be a candidate for monitoring response to treatment, but it may be less than ideal considering the increased PSMA expression under hormonal manipulation. Dr. Walz remarks that if molecular imaging will ultimately assist with treatment monitoring, we need to understand what tracers suit which drug in which situation. Furthermore, there are certainly cost implications considering that these monitoring algorithms may require monthly PET scans. 

Dr.  Walz concluded with several highlights from his presentation, (i) current PET tracers are an improvement, although there clearly remains a need for more sensitive and specific tracers, (ii) there certainly is a need for effective treatment and monitoring, and (iii) costs and resource management need to be a consideration. 

Speaker: Jochen Walz, Institut Paoli-Calmettes, Marseille, France 

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md at the EAU - Update on Prostate Cancer  – September 15-16, 2017, Vienna, Austria


1. Maurer T, Gschwend JE, Rauscher I, et al. Diagnostic efficacy of (68)Gallium-PSMA Positron Emission Tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016;195(5):1436-1443. 
2. Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 68Ga-Prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: A systematic review and meta-analysis. Eur Urol 2016;70(6):926-937.
3. Bach-Gansmo T, Nanni C, Nieh PT, et al. Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine (18F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate cancer. J Urol 2017;197(3 Pt 1):676-683.