Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial

JAMA Oncol. 2019 Jun 1;5(6):856-863. doi: 10.1001/jamaoncol.2019.0096.

Abstract

Importance: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging.

Objective: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial.

Design, setting, and participants: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard.

Main outcomes and measures: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety.

Results: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients.

Conclusions and relevance: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer.

Trial registration: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging*
  • Neoplasm Recurrence, Local / therapy
  • Oligopeptides / therapeutic use*
  • Positron-Emission Tomography*
  • Predictive Value of Tests
  • Prostate-Specific Antigen
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / therapy
  • Radiopharmaceuticals / therapeutic use*

Substances

  • Oligopeptides
  • Radiopharmaceuticals
  • gallium 68 PSMA-11
  • Edetic Acid
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT02940262
  • ClinicalTrials.gov/NCT03353740