An investigational radiotracer that targets prostate-specific membrane antigen is being tested in patients with high-risk, recurrent, or metastatic prostate cancer to determine whether the novel agent can improve upon the sensitivity and specificity of conventional imaging.
Kenneth J. Pienta, MD
An investigational radiotracer that targets prostate-specific membrane antigen (PSMA) is being tested in patients with high-risk, recurrent, or metastatic prostate cancer to determine whether the novel agent can improve upon the sensitivity and specificity of conventional imaging.
The phase II/III OSPREY trial (NCT02981368) is evaluating 18F-DCFPyL (PyL) injection administered in conjunction with a positron emission tomography/computed tomography (PET/CT) scan in men with at least high-risk prostate cancer who are candidates for radical prostatectomy with lymphadenectomy (cohort A) or in patients with locally recurrent or metastatic disease willing to undergo biopsy (cohort B). The trial is seeking to enroll approximately 300 men in the United States and Canada (Figure).
“We are looking at men with high-risk prostate cancer to determine if they potentially have cancer that has escaped the prostate and is in the lymph nodes already, as well as in patients who have metastatic disease, to see whether this agent can better define where their cancer has spread,” said principal investigator Kenneth J. Pienta, MD, the Donald S. Coffey Professor of Urology and director of research at the James Buchanan Brady Urological Institute at Johns Hopkins Medicine in Baltimore, Maryland.
PyL is a second-generation uorine-18-labeled small-molecule PSMA inhibitor that targets prostate cancer cells. It is under study in this setting specifically because of how it performs compared with other imaging agents, namely F18 PET, which is typically used in PET scans because it attaches to glucose, showing where the tumor cells are located, Pienta said. Prostate cancer cells do not take up glucose very well; this new “linked” version of the agent can detect PSMAs, enabling clinicians to combine PET and CT scans to localize the cancer in 3 dimensions, according to Pienta.
The agent is injected intravenously at about 9 mCi per patient, per scan, the optimal dose for an effective imaging scan. There are no adverse events (AEs) associated with PyL because “it’s just like a PET scan,” Pienta said.
Prior research has shown that PyL is safe, with high accumulation in presumed primary and metastatic foci, a radiation dose similar to other PET tracers, and no observed radiotracer-specific AEs.1 In an earlier study, PyL was compared with conventional imaging in men with postprostatectomy serum prostate-specific antigen (PSA) levels of ≥0.2 ng/mL.2 Participants were imaged with CT or magnetic resonance imaging and bone scans, as well as with PyL PET/CT; conventional imaging results were examined by reviewers blinded to findings with the novel agent.
Among 12 men with a median PSA of 0.34 ng/m L (range, 0.2-11), 9 patients had areas of detectable disease with PyL PET/CT imaging, including 3 with local recurrence, 3 with lymph node metastases, 2 with bony lesions, and 1 with both lymph node and bony findings. By contrast, conventional imaging found that only 4 of the participants had at least 1 site of disease. Notably, the novel imaging method detected all lesions evident on conventional imaging.
“So far, our preliminary data would suggest it is much more sensitive and specific for detecting prostate cancer than conventional CT scans or bone scans,” Pienta said. “That’s why we believe that we need to prove that with this study so it can become FDA approved.”
Broad Use Envisioned
The clinical need for better imaging techniques for patients with prostate cancer is clear, particularly since conventional scanning results are frequently inconclusive or show false-negatives.2 “For example, in a man with a rise in PSA after a prostatectomy, by conventional bone scan or CT scan, we can’t find the cancer. Therefore, we’re using PSMA PET to see if we can find where the recurrence is, and that helps us dictate whether we can hit that with radiation versus whether the patient has a lot of disease and needs hormone therapy,” Pienta said.
In the setting of high-risk prostate cancer, where the patient has multiple lymph nodes positive for disease that cannot be surgically removed, more accurate imaging could be essential to determining the course of treatment, added Pienta.
Pienta sees broad potential for the future use of PyL PET/CT imaging in prostate cancer. He also is the principal investigator for the UTILITY trial (NCT02825875), in which PyL PET/CT will be made available to urologists, medical oncologists, and radiation oncologists treating patients with a range of clinical indications in prostate cancer at Johns Hopkins.
“As a caregiver and a physician, I believe that this study will impact the management of patients with prostate cancer because it’s going to help us find their disease better than any current imaging agent, and that will guide therapy in multiple different ways,” said Pienta, in reference to the UTILITY study.
If the OSPREY trial is successful, the results will help support an FDA application for use of the agent, according to Progenics Pharmaceuticals, Inc, which is developing PyL PET/CT.