PSMA-targeted PET with [68Ga]Ga-P16-093: Assessment of potential role in surgical planning for patients with intermediate-risk and high-risk prostate cancer. (2020)

1252 Objectives: To assess how PSMA-targeted PET with [68Ga]Ga-P16-093 could influence surgical planning for patients with intermediate-risk or high-risk prostate cancer
 Methods: [68Ga]Ga-P16-093 PET/CT was performed on 10 prostate cancer patients who were independently scheduled for prostatectomy based on clinical presentation and the results of standard-of-care mpMRI and template biopsy (8 patients with intermediate risk disease; 2 patients with high-risk disease). Following a CT scan for attenuation correction, list-mode PET imaging (0-55 minutes) was initiated upon i.v. administration of [68Ga]Ga-P16-093 (216 ± 6 MBq; IND 133,222). The PET acquisition covered a single bed position ranging from above the iliac crest to the lower pelvis (extended field-of-view Siemens Biograph mCT scanner). Standard iterative reconstructions were performed over various framing periods (0-5, 5-10, 10-15, 15-40, 40-50, and 5-50 minutes, as well as 3-8, 3-13, 3-23, 3-28, 3-33, 3-38, 3-43, and 3-55 minutes), with the goal of maximizing observed counts while avoiding possible interference from urine radioactivity progressively accumulating in the bladder. In addition to standard surgical pathology, whole-mount prostate pathology was obtained for 8 of the 10 subjects. A radiologist with board certification in nuclear medicine reviewed the PET/CT images to assess the location and extent of suspected cancerous tissue. Secondarily, a urologist reviewed the images to evaluate whether PET-derived knowledge of disease location might alter the surgical approach, e.g., by guiding a decision to spare vascular nerve bed(s) to diminish morbidity (incontinence and erectile dysfunction).
 Results: [68Ga]Ga-P16-093 PET/CT images were read as positive in 8 of the 10 subjects, defining the location of numerous PSMA-avid lesions within the prostate. Bladder radioactivity was not judged to interfere with image interpretation, even when framed to incorporate all counts over the 55-minute period post-injection. In post-surgical pathology for the index lesions, one patient with high-risk disease had a primary Gleason 4+5 (70%:30%) lesion that was highly tracer-avid, as well as numerous PET-positive lymph nodes that were also confirmed positive for disease. Five subjects had Gleason 4+3 disease, all with lesions readily identified in the PET images. Three subjects had Gleason 3+4 disease; and one had Gleason 3+3 disease. PET was positive in two of the Gleason 3+4 subjects whose disease was reported as Gleason 3 (73%):Gleason 4 (25%):Gleason 5 (2%), and Gleason 3 (80%):Gleason 4 (15%):Gleason 5 (5%); but, was negative for the other Gleason 3+4 subject, reported as Gleason 3 (95%):Gleason 4 (5%). PET was also negative in the subject with Gleason 3+3 disease. The location of PSMA-expressing lesions within the prostate often had significance for surgical planning, improving confidence that a nerve bundle could be spared in five of the subjects, due to no nearby tracer accumulation. In two of those subjects, knowledge of regional PSMA expression would also alter surgical planning around bladder neck resection. In one patient, [68Ga]Ga-P16-093 PET showed high accumulation in the vicinity of a nerve bundle, with post-surgical pathology confirming extracapsular extension (ruling-out nerve sparing). For the remaining four subjects, [68Ga]Ga-P16-093 PET/CT findings would have produced no change in surgical plans. Importantly, no patient had a positive margin on the side of the prostate where [68Ga]Ga-P16-093 PET was negative.
 Conclusions: [68Ga]Ga-P16-093 appears useful for pre-prostatectomy assessment of patients with intermediate- or high-risk prostate cancer to better define the regional location(s) of disease. In this initial assessment, PET-derived knowledge of regional PSMA expression would have modified surgical planning in 6 of the 10 patients. (Supported by NIH/NCI R44CA233140.)