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Invited Commentary
September 16, 2021

Prostate-Specific Membrane Antigen Positron Emission Tomography and the New Algorithm for Patients With Prostate Cancer Prior to Prostatectomy

Author Affiliations
  • 1Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, New York
  • 2Meyer Cancer Center, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
  • 3Department of Urology, Weill Cornell Medicine, New York, New York
  • 4Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
JAMA Oncol. 2021;7(11):1642-1643. doi:10.1001/jamaoncol.2021.3762

After several decades of development of prostate-specific membrane antigen (PSMA) as a biomarker for prostate cancer, a recent series of studies have defined its diagnostic clinical significance in patients with prostate cancer, including prior to radical prostatectomy, as in the diagnostic imaging study by Hope et al1 in this issue of JAMA Oncology. Importantly, these data comport with a similarly designed prospective trial evaluating PSMA positron emission tomography (PET) diagnostic performance of a similar agent (18F-DCFPyL) in cohort A of the OSPREY trial.2 There is a clear message from both trials: clinicians taking care of patients with high-risk prostate cancer being assessed for prostatectomy can use a positive PET scan as a true positive (0.95 [95% CI, 0.92-0.97]1 vs 0.98 [95% CI, 0.94-0.99] in the OSPREY trial2), whereas a negative scan cannot be used to exclude disease or inform nodal dissection (both studies had a diagnostic sensitivity near 40%). One methodologic issue to mention is that clinicians were not blinded to PSMA PET results, and patients with evidence of extraprostatic disease may not have gone on to surgery. Post hoc analysis of these “negative” PET studies in both investigations also have a common message. Both demonstrate that many of the false-negative studies are found in patients who have pathologically PSMA-positive lymph nodes that are smaller than 1.0 cm or 0.5 cm, below the resolution of this technology. These truly micrometastatic lesions may have a better prognosis than those identified by imaging and lead to the hypothesis that these are likely the patients with long-term benefit from surgical resection.

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