Background: Circulating tumor cells (CTC) detection and androgen receptor splice variant 7 (ARV7) expression have been shown to be associated with worse clinical outcomes in metastatic castration resistant prostate cancer (mCRPC) patients undergoing androgen receptor targeted agents (ARTA) treatment, paving the way for alternative treatment options for patients with negative predictive factors. Full-length androgen receptor (ARFL), prostate specific membrane antigen and prostate specific antigen (PSA) may further help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCRPC undergoing ARTA treatment (PRIMERA trial, NCT04188275) terminated the planned enrollment in 2020. Here we present early results of the overall cohort. Methods: PRIMERA (NCT04188275) is a prospective, observational trial enrolling mCRPC patients undergoing ARTA treatment. All patients were treated with either abiraterone or enzalutamide in I line setting. Blood samples to detect CTCs were taken before starting ARTA treatment. Reverse transcription - quantitative real-time PCR (RT-qPCR) was used to determine the CTC expression of PSA, PSMA, AR and ARV7. PSA drop (defined as difference between baseline PSA at ARTA treatment start and PSA at nadir under treatment), progression free and overall survival (PFS and OS) and their correlation with CTC detection were reported. Explorative analysis about AR, PSA and PSMA expression in CTC+ patients were conducted. Results: Overall, 44 patients were included. CTC were detected at treatment start in 19 patients (43,2%), of whom 3(15,78%), 9(63,15%), 15(78,94%) and 14 (73.68%) patients expressed ARV7, ARFL, PSA and PSMA, respectively. Biochemical response was significantly improved in CTC+ vs. CTC- patients, with median PSA drop values of 18.5 vs 2.5 ng/ml (p=0.03). After a median follow up of 18 months, 22 (50%) patients progressed. PFS was significantly longer in CTC- patients (not reached vs 16 months, respectively, p=0.02). Eight (18.2%) patients died, a non-significant trend in terms of overall survival was detected in favor of CTC- patients (not reached vs 29 months, respectively, p=0.05). AR, PSA and PSMA expression in CTC+ had no significant impact on PSA drop, PFS or OS. Conclusions: PRIMERA trial confirmed the CTC detection predictive importance in mCRPC patients. Adequately powered studies will be needed to further explore CTC profiling in this setting. Clinical trial information: NCT04188275.