Prostate-specific antigen (PSA) decline has been proposed as a prognostic marker in metastatic hormone-sensitive prostate cancer (mHSPC). We aimed to evaluate whether a ≥90% PSA decline (PSA 90) predicts overall survival (OS) in patients treated with apalutamide plus androgen deprivation therapy (ADT) in real-world practice. Design, setting, and participants; Intervention (include if there are any).
We conducted a multicenter retrospective study including patients with mHSPC treated with apalutamide plus ADT in 17 hospitals. PSA 90 was defined as a ≥90% decline from baseline within 3 or 6 mo or PSA <0.02 ng/ml. To evaluate the effect of PSA response, a landmark analysis was performed at 3 and 6 mo. We evaluated OS and radiographic progression-free survival (rPFS). Multivariable Cox regression analyses were adjusted for age, baseline PSA, disease presentation (de novo vs recurrent), volume (CHAARTED), and risk (LATITUDE).
Between May 2018 and September 2024, 1022 patients with mHSPC were included in the Real-World Evidence APA database. The median age was 68.5 yr (interquartile range [IQR] 62.7-74.6) and baseline PSA 8.2 ng/ml (IQR 1.8-41.1). At 3 mo, 807 patients (87%) achieved a PSA 90 response; at 6 mo, 773 patients (88%) were PSS 90 responders. PSA 90 response at 3 and 6 mo was associated with a statistically significant lower hazard of OS (hazard ratio [HR] = 0.31, 95% confidence interval [CI] = 0.19-0.51). Similar results were observed for PSA 90 at 6 mo (HR = 0.29, 95% CI = 0.17-0.48). PSA 90 response at 3 and 6 mo was also associated with a statistically significant lower hazard of rPFS response (HR = 0.46, 95% CI = 0.31-0.69, and HR = 0.41, 95% CI = 0.26-0.63, respectively). Limitations include the retrospective design, potential selection bias, incomplete PSA measurements, heterogeneity in imaging, and shorter follow-up, which may affect the precision and generalizability of our findings.
PSA 90 response at 3 and 6 months is a strong prognostic marker for overall survival and radiographic progression-free survival in patients with metastatic hormone-sensitive prostate cancer treated with apalutamide. These findings support PSA 90 as an early prognostic indicator for clinical risk stratification. Patient summary: We studied how blood levels of PSA change in men with advanced prostate cancer treated with apalutamide. Patients whose PSA dropped by 90% or became undetectable within 3 or 6 mo lived longer, suggesting that early PSA reduction can help predict better outcomes.
European urology open science. 2026 Apr 20*** epublish ***
Ana Guijarro, Estíbaliz Jiménez, Antoni Vilaseca, Estefanía Linares, Raquel Sopeña, Pedro De Pablos-Rodríguez, Bernardo Herrera, Darío Vázquez-Martul Pazos, Natalia Picola, Juan Gómez Rivas, Mario Domínguez Esteban, Marc Costa Planells, Ángeles Sanchis Bonet, Nagore García Expósito, Meritxell Pérez Márquez, José Manuel De la Morena, Jesús Muñoz Rodríguez, Pol Servián Vives, Virginia Hernández, Enrique De la Peña, Laura Resa, Carlos Llorente
Hospital Universitario Fundación Alcorcón, Alcorcón, Spain., Hospital Clínic de Barcelona, Barcelona, Spain., Hospital Universitario La Paz, Madrid, Spain., Hospital Universitario 12 de Octubre, Madrid, Spain., Fundación Instituto Valenciano de Oncología, Valencia, Spain., Hospital Universitario Virgen de la Victoria, Málaga, Spain., Complejo Hospitalario Universitario de A Coruña, A Coruña, ES, A Coruña, Spain., Hospital Universitari de Bellvitge, Barcelona, Spain., Hospital Clínico San Carlos, Madrid, Spain., Hospital Universitario Marqués de Valdecilla, Santander, Spain., Hospital Vall d'Hebron, Barcelona, Spain., Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain., Instituto Catalán de Oncología, Barcelona, Spain., Consorcio Sanitario de Terrassa, Terrassa, Barcelona, Spain., Hospital Universitario Infanta Sofía, Madrid, Spain., Parc Taulí Hospital Universitari, Barcelona, Spain., Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.