Phase 2/3 study demonstrates value of PSMA imaging agent for prostate cancer staging

Results from the phase 2/3 OSPREY study showed that the prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging agent 18F-DCFPyL (Pylarify, Lantheus) is highly sensitive and specific for localizing prostate cancer in newly diagnosed high-risk patients and among men being monitored for disease recurrence and metastasis.

Based on its diagnostic performance in OSPREY and in CONDOR, a phase 3 study enrolling men with biochemical recurrence of prostate cancer who had uninformative standard imaging, PET/CT imaging with this recently FDA-approved tracer is expected to transform the landscape for evaluation and management of men with prostate cancer, according to Kenneth J. Pienta, MD.

Pienta, professor of urology and oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, is lead author of the recently published article reporting results of OSPREY.¹ He told Urology Times,“18F-DCFPyL-PET/CT will change the diagnostic work-up for high-risk and recurrent prostate cancer, replacing conventional bone scans and standard CT imaging. It will also re-define ‘biochemical recurrence’ and furthermore, identify patients who may benefit from PSMA-based therapeutics.”

The availability of this powerful imaging agent also raises new considerations for how to approach patient care.

“With 18F-DCFPyL-PET/CT, we can find metastatic disease much sooner. Therefore, 1 question that will need to be addressed is: what do we do now?” said Pienta.

“For example, do we treat PSMA-oligometastatic disease with targeted stereotactic body radiation therapy, or is a positive scan showing us systemic disease earlier? And if systemic, do we need to treat?”

The OSPREY study investigated 18F-DCFPyL in 2 patient cohorts. The first comprised men with high-risk prostate cancer who were undergoing radical prostatectomy with extended template pelvic lymph node dissection. The second cohort enrolled previously treated men with evidence of local recurrence outside the confines of prior treated site(s) or new or progressive metastatic disease demonstrated by CT/MRI, ultrasound, or whole-body bone scan.

All patients received a single intravenous dose of 9 mCi 18F-DCFPyL administered 1 to 2 hours before PET/CT. The results of the radiopharmaceutical imaging were evaluated independently by 3 blinded, central readers.

In the high-risk cohort, which included 252 evaluable patients, detection of pelvic nodal disease with 18F-DCFPyL-PET/CT was compared with histopathology findings from examination of nodal packets collected at lymphadenectomy. In this cohort, 18F-DCFPyL–PET/CT showed a specificity of 96 to 99% across the 3 readers, sensitivities of 31% to 42%, positive predictive values (PPVs) of 78% to 91%, and negative predictive values (NPV) of 81% to 84%.

Although OSPREY did not meet its sensitivity end point in the high-risk cohort, the criterion for sensitivity success was met in a post hoc analysis that evaluated its detection of nodal metastases greater than 5 mm in diameter. Done based on the assumption that smaller tumor deposits were below PET detection limits, the post hoc analysis showed 18F-DCFPyL-PET/CT had a sensitivity of 60% and the same specificity (98%) as in the overall group.

In the second cohort of men, the findings from histopathology examination of tissue obtained from image-guided biopsy of at least one amenable lesion identified on conventional imaging was used as the reference standard for evaluating the performance of 18F-DCFPyL-PET/CT. In this cohort, 18F-DCFPyL had sensitivities of 93% to 99% and PPVs of 81% to 88%.

Sensitivity of the radiopharmaceutical imaging exceeded 88% and its PPV was 75% or higher in analyses examining detection of prostate cancer in different anatomic sites. Subgroup analyses done with men stratified by baseline PSA showed that 18F-DCFPyL PET/CT maintained good performance in detecting disease even in men with a baseline PSA lower than 2 ng/mL.

No significant safety issues emerged and 18F-DCFPyL was well-tolerated. A total of 51 (13.2%) men experienced at least 1 adverse event (AE). The only AEs occurring at a rate of 2% or higher were dysgeusia (2.1%) and headache (2.1%). There were no serious AEs considered related to 18F-DCFPyL.

Reference

1. Pienta KJ, Gorin MA, Rowe SP, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol. 2021;206(1):52-61. doi:10.1097/JU.0000000000001698