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Fendler, Wolfgang P.; Weber, Manuel; Iravani, Amir; Hofman, Michael S.; Calais, Jeremie; Czernin, Johannes; Ilhan, Harun; Saad, Fred; Small, Eric J.; Smith, Matthew R.; Perez, Paola M.; Hope, Thomas A.; Rauscher, Isabel; Londhe, Anil; Lopez-Gitlitz, Angela; Cheng, Shinta; Maurer, Tobias; Herrmann, Ken; Eiber, Matthias and Hadaschik, Boris (2019): Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer. In: Clinical Cancer Research, Vol. 25, No. 24: pp. 7448-7454

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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 (kappa: 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.

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