Abstract
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. 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. 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). 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.
Highlights
Nonmetastatic castration-resistant prostate cancer is characterized by a rising prostate-specific antigen (PSA) level, castrate testosterone levels, and no evidence of distant metastases by conventional bone scan and cross-sectional imaging of the chest, abdomen, and pelvis [1]
Prostate-specific membrane antigen ligand (PSMA)-PET detected any disease in most patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSA doubling time (PSADT) of 10 months and Gleason score of 8
We further evaluated the efficacy of systemic therapy in patients who had risk factors for distant metastases (M1 disease) detected by PSMA-PET in the SPARTAN study population
Summary
Nonmetastatic castration-resistant prostate cancer (nmCRPC) is characterized by a rising prostate-specific antigen (PSA) level, castrate testosterone levels, and no evidence of distant metastases by conventional bone scan and cross-sectional imaging of the chest, abdomen, and pelvis [1]. One-third of patients with nmCRPC develop distant metastases on conventional imaging within 2 years despite ongoing androgendeprivation therapy In patients with nmCRPC, short PSA doubling time (PSADT) has been associated with worse clinical outcomes than longer PSADT [2,3,4]. Delaying the development of metastasis is an important treatment goal that can be achieved with early inhibition of androgen receptor signaling. Several androgen receptor inhibitors added to ongoing ADT have recently been shown to improve outcomes in nmCRPC. Apalutamide and enzalutamide have been approved for the treatment of nmCRPC based on demonstration of a significant improvement in metastasis-free survival (MFS) in the SPARTAN and PROSPER studies [5, 6]. Darolutamide has been shown to significantly prolong MFS in nmCRPC in the ARAMIS study [7]. With the recent advent of new PET technologies, conventional imaging is a diagnostic tool that
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