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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant
Wolfgang P Fendler1,2, Manuel Weber3, Amir Iravani4
1University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany. wolfgang.fendler@uk-essen.de.
Purpose:
Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET.
Experimental Design:
We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease.
Results:
PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81-0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P < 0.05).
Conclusions:
PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.
Insights
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) detects cancer in most nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. This imaging identified distant metastases in 55% of nmCRPC patients, impacting treatment decisions.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiology
Background:
- Systemic androgen-signaling inhibition improves outcomes for nonmetastatic castration-resistant prostate cancer (nmCRPC).
- Prostate-specific membrane antigen positron emission tomography (PSMA-PET) offers higher sensitivity than conventional imaging for prostate cancer detection.
- The utility of PSMA-PET in nmCRPC is not well-established.
Purpose of the Study:
- To characterize the cancer burden in high-risk nmCRPC patients using PSMA-PET.
- To evaluate the detection rate of pelvic disease and distant metastases (M1) by PSMA-PET in nmCRPC.
- To identify predictors of PSMA-PET-detected M1 disease.
Main Methods:
- Retrospective analysis of 200 nmCRPC patients with PSA >2 ng/mL and high risk for metastatic disease (PSADT ≤10 months and/or Gleason score ≥8).
- Central review of PSMA-PET scans to assess pelvic disease and M1 disease.
- Stratification of SPARTAN patients by risk factors for PSMA-PET-detected M1 disease.
Main Results:
- PSMA-PET detected disease in 196 of 200 patients (98%).
- M1 disease was identified in 55% of patients despite negative conventional imaging.
- Predictors of M1 disease included PSA ≥ 5.5 ng/mL, pN1, prior primary radiation, and prior salvage radiotherapy.
Conclusions:
- PSMA-PET is highly sensitive for detecting disease in nmCRPC patients, identifying M1 disease in 55% of cases.
- This imaging modality can detect metastases even in patients with favorable risk factors.
- Future studies should evaluate the impact of PSMA-PET imaging on treatment guidance in nmCRPC.
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