BETHESDA, MD USA (UroToday.com) - Dr. Peter Choyke of the National Cancer Institute began his presentation by highlighting the epidemiology of prostate cancer: approximately 187 000 men are diagnosed with low- or intermediate-risk prostate cancer; 26 000 men have relapse of disease after treatment; and 33 000 men die of prostate cancer. These numbers indicate that our efforts should focus on addressing those men with relapse in order to effectively decrease the number of cancer-specific deaths per year. Dr. Choyke identified a “curative window” — a period when identification and treatment of disease recurrence is most likely to improve outcomes—as the time from the beginning of biochemical recurrence when cancer cell count is the lowest. As Kwon et al., PLOS One, 2014 Jul 29;9(7)) demonstrated, patients who receive salvage treatment at a PSA less than 0.5 have a BCR-free survival advantage over those treated at a PSA greater than 0.5. This begs the question, what are our imaging options in patients with biochemical recurrence?
Dr. Choyke listed several MRI options, including conventional, iron oxide, and whole-body diffusion weighted imaging, in addition to multiple novel PET-based modalities that have shown promising data for imaging of patients with biochemical recurrence. Multiparametric MRI, including T2-weighted, apparent diffusion coefficient, and dynamic contrast-enhanced sequences, has shown the ability to identify locally recurrent lesions at PSAs as low as 0.8. Diffusion-weighted imaging has also shown the ability to diagnose bone metastases, often before they are identified on bone scan, as well as lymph node metastases in normal-sized nodes (Thoeny et al., Radiology. 2014 Oct;273(1):125-35). The addition of iron oxide (Ferumoxytol injection) in MR-based imaging has also proven to be useful in finding lymph node metastases.
11C-Choline- PET scan was introduced at the Mayo Clinic, and early studies have shown that is useful in identifying recurrent sites of disease in the setting of biochemical recurrence. The major limitation of 11C-Choline is that it has a 20-minute half-life, and thus must be produced on site. Moreover, it has shown limited sensitivity in men with very low PSAs; one study showed a 5% detection rate at a PSA < 1 (Giovacchini G et al., J Urol. 2010;184(3):938-943).
18Fluorocholine is another novel agent under development in Europe and Australia that has shown some activity in identifying sites of disease in the setting of biochemical recurrence. Early data demonstrates sensitivities that are lower than those seen with 11C-Choline, as men with higher PSAs are diagnosed with recurrent cancer.
FACBC PET-CT is a modality currently under investigation that has demonstrated early results that are superior to 18Fluorocholine and 11C-Choline. Nanni and colleagues published a series comparing FACBC and 11C-Choline, and showed that detection rate of recurrent cancer was 40% vs 20% in favor of FACBC (Eur J Nucl Med Mol Imaging. 2013 Jul;40 Suppl 1:S11-7). False positives, however, can be seen in PIN and BPH. Dr. Choyke presented a patient in whom a 5mm lymph node recurrence and equally small periprostatic lesion were diagnosed using this modality.
Finally, Dr. Choyke discussed the use of DCFBC, an 18F-labeled tracer developed at Johns Hopkins that targets PSMA. DCFBC retains its utility in patients with castrate-resistant disease, and may ultimately be the impetus for the development of PSMA-directed treatment strategies in the future.
Peter Choyke, MD
National Cancer Institute
Nikhil Waingankar, MD* from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA
*Fox Chase Cancer Center, Philadelphia, PA USA