• Nobuaki Matsubara, Kim N Chi, Mustafa Özgüroğlu, Alfredo Rodriguez-Antolin, Susan Feyerabend, Luis Fein, Boris Y Alekseev, Giri Sulur, Andrew Protheroe, Susan Li, Suneel Mundle, Peter De Porre, Namphuong Tran, and Karim Fizazi.
• National Cancer Center Hospital East, Chiba, Japan. Electronic address: nmatsuba@east.ncc.go.jp.
• Eur. Urol. 2020 Apr 1; 77 (4): 494-500.

BackgroundLATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).ObjectiveTo assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).Design, Setting, And ParticipantsA post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.Outcome Measurements And Statistical AnalysisThe associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).Results And LimitationsAAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.ConclusionsSuperior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.Patient SummaryWe found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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