Presentation Authors: Michael A. Gorin*, Kenneth J. Pienta, Baltimore, MD, Barry A. Siegel, St. Louis, MO, Peter Carroll, San Francisco, CA, Frédéric Pouliot, Quebec, Canada, Stephan Probst, Montreal, Canada, Lawrence Saperstein, New Haven, CT, Mark A. Preston, Boston, MA, Ajjai Shivaram Alva, Ann Arbor, MI, Akash Patnaik, Chicago, IL, Jeremy C. Durack, New York, NY, Steven P. Rowe, Baltimore, MD, Melissa Nichols, Tess Lin, Thomas Strack, Vincent A. DiPippo, Syed Mahmood, Jessica Jensen, Vivien Wong, Michael J. Morris, New York, NY
Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed by prostate cancer (PCa) cells and can be targeted using the novel PET radiotracer 18F-DCFPyL. This prospective trial aimed to determine the diagnostic performance of 18F-DCFPyL PET/CT for detecting pelvic lymph node metastases and other distant sites of disease in men with PCa.
Methods: 18F-DCFPyL PET/CT was evaluated in 385 men with high-risk PCa planned for radical prostatectomy and lymphadenectomy (Cohort A, n=268) or radiological evidence of metastatic PCa feasible for biopsy (Cohort B, n=117). 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. The coprimary endpoints of sensitivity and specificity of 18F-DCFPyL PET/CT for detecting pelvic lymph node metastases were evaluated in Cohort A. Secondary endpoints included safety in both cohorts, positive predictive value (PPV) and negative predictive value (NPV) in Cohort A, and sensitivity and PPV in Cohort B. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Histopathology served as the reference standard to which imaging findings were compared.
Results: In Cohort A (n=252 evaluable), the sensitivity of 18F-DCFPyL PET/CT ranged among the three readers from 30.6-41.9% (lower bound of 95% CI: 19.2-29.7%), with a range of specificities of 96.3-98.9% (lower bound of 95% CI: 93.6-96.0%). Additionally, the PPV and NPV ranged from 78.1-90.5% and 81.4-83.8%, respectively. When the analysis was restricted to median lymph node metastases >4 mm, there was a marked improvement in sensitivity (range 50.0-66.7%; lower bound of 95% CI: 32.0-49.8%). In patients with distant metastatic PCa (Cohort B, n=93 evaluable), the values of sensitivity and PPV ranged from 92.9-98.6% (lower bound of 95% CI: 84.0-91.6%) and 81.2-87.8%, respectively. No drug-related serious adverse events were observed and 27 (7.0%) men experienced â‰¥1 drug-related adverse event, with dysgeusia (2.1%) and headache (2.1%) being most common.
Conclusions: 18F-DCFPyL PET/CT was well tolerated and demonstrated high overall diagnostic performance in the detection of pelvic lymph node metastases and other distant sites of metastatic disease, as evidenced by its high specificity and PPV. These data suggest that 18F-DCFPyL PET/CT could enable more accurately informed treatment choices in men with prostate cancer. ClinicalTrials.gov identifier NCT02981368.
Source of Funding: Progenics Pharmaceuticals, Inc.