No abstract

Purpose: Our goal was to review the pathway and pertinent materials leading to approval of prostate-specific membrane antigen (PSMA) scanning by the U.S. Food and Drug Administration (FDA). Materials and Methods: Beginning with the pivotal trials and working backward, we summarize the evolution of PSMA scanning, beginning with the discovery of the molecule, the mechanism of action to identify prostate cancer, the route to the present-day test and some of the major publications leading to each step of the sequence. From the thousands of PSMA articles listed on PubMedÒ, the present review is focused on the 4 large U.S. trials incorporating university studies of the gallium-68 compound and commercial studies of the fluorine-18 compound. The review further focuses on the role of PSMA scanning for both initial staging of prostate cancer and diagnosis of recurrent prostate cancer. Results: PSMA is a transmembrane-bound glycoprotein which is overexpressed by 100e1,000-fold in prostate cancer cells. Preclinical PSMA studies at Cornell and Johns Hopkins in the 1990s were followed by early human studies in Germany in the early 2010s, then pivotal clinical trials at

Background Partial gland ablation (PGA) is a new option for treatment of prostate cancer (PCa). Cryotherapy, an early method of PGA, has had favorable evaluations, but few studies have employed a strict protocol using biopsy endpoints in men with clinically significant prostate cancer (csPCa). Methods 143 men with unilateral csPCa were enrolled in a prospective, observational trial of outpatient PGA‐cryotherapy. Treatment was a 2‐cycle freeze of the affected prostate part. Participants were evaluated with MRI‐guided biopsy (MRGB) at baseline and at 6 months and 18 months after treatment. Absence of csPCa upon MRGB was the primary endpoint; quality‐of‐life at baseline and at 6 months after treatment was assessed by EPIC‐CP questionnaires in the domains of urinary and sexual function. Results Of the 143 participants, 136 (95%) completed MRGB at 6 months after treatment. In 103/136 (76%), the biopsy revealed no csPCa. Of the 103, 71 subsequently had an 18‐month comprehensive biopsy; of the 71 with 18‐month biopsies, 46 (65%) were found to have no csPCa. MRI lesions became undetectable in 96/130 (74%); declines in median serum PSA levels (6.9 to 2.5 ng/mL), PSA density (0.15 to 0.07), and prostate volume (42 to 34cc) were observed (all p < 0.01). Neither lesion disappearance on MRI nor PSA decline correlated with biopsy outcome. Urinary function was affected only slightly and sexual function moderately. Conclusion In the near to intermediate term, partial gland ablation with cryotherapy was found to be a safe and moderately effective treatment of intermediate‐risk prostate cancer. Eradication of cancer was better determined by MRI‐guided biopsy than by MRI or PSA.