ASCO 2018: Accuracy of 68Ga-PSMA11 PET/CT on Recurrent Prostate Cancer: Preliminary Results from a Phase 2/3 Prospective Trial

Chicago, IL (UroToday.com)  68Ga-PSMA11 PET/CT has emerged as one of the most important molecular imaging modalities that is changing the way we diagnose, follow and treat prostate cancer. Certainly, detection of positive lesions on PSMA PET/CT (typically in biochemically recurrent or advanced disease) occurs at much lower PSA levels than traditional bone scan or CT of the abdomen and pelvis. A recently published systematic review and meta-analysis was performed to assess the sensitivity and specificity profiles of 68Ga-PSMA11 PET/CT [1]. Among sixteen studies involving 1309 patients, the overall percentage of positive 68Ga-PSMA PET scans was 40% (95%CI 19-64%) for primary staging and 76% (95%CI 66-85%) for BCR. Positive 68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA; the PSA category-specific positivity for imaging was: 

  •  0-0.2 ng/ml: 42%
  • 0.2-1 ng/ml: 58%
  • 1-2 ng/ml: 76%
  • >2 ng/ml: 95% 
On a per-patient analysis, the summary sensitivity and specificity were both 86%, and on a per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. As Dr. Fendler notes, for approval and reimbursement, accuracy needs to be established in a prospective study employing independent lesion validation. At today’s ASCO 2018 annual meeting, Dr. Fendler presented the initial results of a prospective trial validating the accuracy of 68Ga-PSMA11 PET/CT.

For this phase II prospective trial, patients with biochemically recurrent prostate cancer after primary radical prostatectomy (n = 205) or radiation therapy (n = 45) underwent 68Ga-PSMA11 PET/CT. Presence of prostate cancer was recorded on a patient and region base, including the prostate bed, pelvis, extra-pelvic, and bone. Lesions were validated in 51% of PET/CT-positive patients by histopathology (n = 33), imaging (n = 62) and/or PSA after targeted radiation therapy (n = 9 patients). PSA response after 68Ga-PSMA11 PET/CT guided focal salvage therapy (surgery or radiotherapy) was recorded in 23 of 25 patients treated.  The main outcomes of this study were positive predictive value (PPV), detection rate and outcome.

Among the 250 patients enrolled, the baseline patient characteristics is as follows:

  • Median age: 68 years (range 44-88)
  • Median PSA: 1.9 ng/dL
  • 34% had Gleason ≥8 disease
The overall PPV validated by histopathology was 85% on a patient base (primary endpoint), whereas PPV as determined by any type of validation was 85% on a patient basis and 86% on a region basis. 68Ga-PSMA11 PET/CT localized recurrent prostate cancer in 197 of 250 (79%) patients. The detection results stratified by PSA level are as follows: 

  • 41% for < 0.5 ng/ml (n = 54)
  • 66% for 0.5 to < 1.0 ng/ml (n = 38)
  • 86% for 1.0 to < 2.0 ng/ml (n = 36)
  • 96% for 2.0 to < 5.0 ng/ml (n = 55)
  • 99% for ≥5.0 ng/ml (n = 67)
Lesion location was in 35% in the prostate bed, 61% in the pelvis, 35% in the extra-pelvic region, and 31% in the bone. Following focal salvage therapy alone, 18 (78%) patients had a PSA drop of 50% or more, and 7 (30%) patients had biochemical complete response (PSA undetectable).

The detection rates for this trial in the recurrent prostate cancer setting are comparable to the previously published systematic review and meta-analysis [1]. 

Based on this clinical trial, Dr. Fendler made several take-home points: 

  • • Using an independent reference standard, 68Ga-PSMA11 PET/CT had high PPV for localization of recurrent prostate cancer. 
  • PET/CT guided salvage therapy resulted in high biochemical response rates. 
  •  Pooled multicenter findings (from UCLA and UCSF) will be submitted for a New Drug Application. 

Clinical trial information: NCT02940262

References:
1. Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 68GA-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: A systematic review and meta-analysis. Eur Urol 2016;70(6):926-937.

Presented by: Wolfgang Fendler, MD, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA

Co-Authors: Jeremie Calais, Jeannine Gartmann, Nicholas George Nickols, Robert Evan Reiter, Matthew Rettig, Thomas A Hope, Roger Slavik, Pawan Gupta, Andrew Quon, Martin Allen-Auerbach, Ken Herrmann, Johannes Czernin, Matthias Eiber; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA; University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA; University of California Los Angeles, Los Angeles, CA; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA; Department of Nuclear Medicine, University of California, Los Angeles, Los Angeles, CA; Stanford University, Stanford, CA; Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, DE; University of California, Los Angeles, Los Angeles, CA; Rechts der Isar University Hospital, Technical University of Munich, Munich, Germany


Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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