AUA 2018: Phase II Clinical Trial in Prostate Cancer Evaluating 68Ga-PSMA-11 Detection on both Preoperative PET-CT and Immediate Postoperative Specimen Scanning

San Francisco, CA ( Active surveillance and focal therapy for prostate cancer depend on accurate biopsies for safe and effective treatment. Second, whole gland therapy, such as prostatectomy or radiation therapy, also depend on accurate biopsies for negative margins and precise application of radiation. As such, the question is: What does PSMA PET-CT see and not see in prostate cancer? PSMA PET-CT imaging has shown utility in locating biochemical recurrences in prostate cancer but has rarely been applied to preoperative staging or intraoperative surgical guidance. Clint Bahler, MD and colleagues from Indiana University presented results of their phase II clinical trial assessing how staging PSMA PET-CT informs treatment decisions, as well as evaluate intraoperative dosing of 68Ga-PSMA-11 for immediate postoperative detection of prostate cancer. Preliminary data suggest that PSMA PET-CT SUV correlates with Gleason grade: 3+3 – SUV 4.6; 3+4 – SUV 5.6; 4+3 – SUV 11.6; 4+4 – SUV 13.9; 4+5 – SUV 17.0 [1].

For this prospective, single arm, phase II clinical trial, men with Gleason grade ≥4+3, negative conventional staging, and scheduled for robotic prostatectomy were screened for inclusion. Enrolled patients received a 68Ga-PSMA-11 PET-CT scan for preoperative staging. Intraoperatively, 68Ga-PSMA-11 was re-dosed 30-60 min before taking the prostatic pedicle, and the extirpated prostate specimen was scanned with a high-resolution (1mm) small bore animal PET scanner. A subset of patients (n=5) had their specimen bivalved and evaluated with a 3mm beta-ray hand probe. The prostate was evaluated with whole-mount pathologic processing for intra-lesion analysis and registration with PET imaging. As follows is a representation of the preop PSMA PET-CT, ex-vivo PSAM PET on the prostate gland, and the whole mount pathology correlation:

The median age of 10 patients enrolled was 63.5 years and median PSA was 8.1ng/mL. 

The final pathologic Gleason was: 4+5/5+4 (n=4), 4+3 (n=3), and 3+4 (n=3). Positive PET lesions were seen all 10 cases. Stratifying detection by Gleason, all ≥Gleason 4+3 cases were detected by PSMA-PET, whereas 2/3 of Gleason 3+3 cases were detected. The staging PSMA-PET accurately predicted seminal vesicle invasion (pT3b) in 4a of 5 patients and 5 of 5 when utilizing the immediate postoperative high-resolution scanner. The staging PSMA-PET accurately predicted 1 of 2 lymph node invasions. The detected node was 6mm and the missed node was 2mm. The median (IQR) SUVmax for intraprostatic cancer was 10.6 (8-13) and for benign prostate was 3.8 (3-5). The PSMA-PET images showed good registration with whole-mount pathology for Gleason ≥4+3 (n=7). For Gleason 3+4 (n=3), PSMA-PET detected lesions with %pattern 4 of 20% and 30% while missing a 10% pattern 4. Gleason pattern 3 was not seen by PSMA-PET. Unfortunately, the beta hand probe did not consistently detect positive cancer margins.
Dr. Bahler concluded that based on this pilot study, 68Ga-PSMA-11 clinical staging could aid in surgical planning as it accurately detected Gleason patterns ≥4+3 and predicted seminal vesical invasion. Further study is needed to determine the minimal % pattern 4 that can be detected with PSMA-PET. Dr. Bahler finished with a quote from one of his radiology colleagues “Reading prostate MRI is solving a puzzle. PSMA is like looking at the back page to read the answer.

Presented by: Clinton Bahler, Indiana University, Indianapolis, IN
Co-Authors: Mark Green, Gary Hutchins, Liang Cheng, James Fletcher, Temel Tirkes, Michael Koch, Indianapolis, IN

1. Koerber SA, Utzinger MT, Kratochwil C, et al. 68Ga-PSAM-11 PETCT in newly diagnosed carcinoma of the prostate: Correlation of Intraprostatic PSMA uptake with several clinical parameters. J Nucl Med 2017;58(12):1943-1948.

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA