However, no prospective, multicenter, controlled, multi-blinded and independent central reader studies have been published with these agents. Prostate-specific membrane antigen (PSMA) is overexpressed by prostate cancer cells and PSMA-based PET has demonstrated high positive predictive value and negative predictive value for identifying regional and distant metastases. The reported per-patient sensitivity and specificity with PSMA PET/CT for regional nodal staging ranges from 33-100% and 80-100%, respectively.2 18F-DCFPyL is a novel PSMA-targeted PET radiopharmaceutical that may improve the accuracy of staging high-risk patients to guide initial therapy planning. At the American Urological Association (AUA) 2020 virtual meeting, Preston Sprenkle, MD, and colleagues presented initial results of the OSPREY trial, a Study of 18F-DCFPyL PET/CT Imaging in Patients With Prostate Cancer (OSPREY), assessing the clinical utility of preoperative PSMA-targeted 18F-DCFPyL PET/CT in men with high-risk prostate cancer.
18F-DCFPyL PET/CT was evaluated in 252 men with high-risk prostate cancer due to undergo radical prostatectomy with pelvic lymphadenectomy. Approximately 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. Sensitivity, specificity, positive predictive value and negative predictive value of 18F-DCFPyL PET/CT for detecting a primary tumor in the gland and pelvic lymph node metastases were compared to conventional imaging, either CT or MRI. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans and one blinded central reader interpreted the conventional imaging. Imaging results were compared to surgical pathology as the truth standard. The OSPREY study design and cohorts are as follows:
Central conventional imaging reader evaluated a total of 247 scans for pelvic lymph node involvement and 245 scans for the primary tumor in the gland.
Among these patients, the median baseline prostate-specific antigen (PSA) was 9.3 ng/mL; 97% of men in Cohort A had no known nodal metastatic disease at the time of study entry, and 99% of subjects had no known distant metastatic disease. Despite similar sensitivity (40.3% for 18F-DCFPyL PET/CT and 41.7% for CI) in detecting N1 disease, the positive predictive value of 18F-DCFPyL PET/CT (86.7%) was nearly 3-fold higher than conventional imaging (29.1%) in identifying true pelvic lymph node metastases. 18F-DCFPyL-PET/CT was more specific than conventional imaging (97.9% vs. 67.3%) and has a higher negative predictive value than conventional imaging (83.2% vs. 78.3%). 18F-DCFPyL-PET/CT was also more sensitive in detecting a primary tumor in the prostate gland, with a sensitivity of 98% compared to 36% for conventional imaging. A total of 7% of patients experienced at least one drug-related adverse event, with the most frequent drug-related adverse event including dysgeusia (2.1%) and headache (2.1%).
Dr. Sprenkle provided the following summary points for initial results from the OSPREY trial:
- In men at high-risk of metastatic disease, 18F-DCFPyL-PET/CT demonstrated high positive predictive value, negative predictive value, and specificity, indicating the PyL is highly informative for staging, which directly informs initial therapy planning
- 18F-DCFPyL-PET/CT improved staging of N and M disease spread when compared to conventional imaging offering significant clinical information to directly impact a treating physician’s strategy for disease management
- When compared to pelvic CT or MRI for determining prostate gland and pelvic lymph node disease, using histopathology as the truth standard, the diagnostic performance of 18F-DCFPyL-PET/CT was superior in identifying the true extent of disease and could guide initial therapy in patients with high-risk prostate cancer
Presented by: Preston C. Sprenkle, MD, Associate Professor of Urology; Division Chief, Division of Urology at VA Connecticut Healthcare System; Director, Urology Research Fellowship; Director, Urologic Oncology Clinical Fellowship Program, Yale University School of Medicine, New Haven, ConnecticutCo-Authors: Peter Carroll, Stephan Probst, Michael A. Gorin, Steven P. Rowe, Kenneth J. Pienta, Frédéric Pouliot, Akash Patnaik, Mark A. Preston, Ajjai Alva, Barry A. Siegel, Michael J. Morris
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.
- Hovels AM, Heesakkers RAM, Adang EM, et al. The diagnostic accuracy of CT and MRI in the Staging of Pelvic Lymph Nodes in Patients with Prostate Cancer: A Meta-Analysis. Clin Radiol 2008 Apr;63(4):387-395.
- Perera M, Papa N, Roberts M, et al. Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-Specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-Analysis. Eur Urol 2020 Apr;77(4):403-417.
Read: ASCO GU 2020: PSMA-targeted 18F-DCFPyL PET/CT Imaging in Patients with Prostate Cancer (OSPREY)