Androgen deprivation therapy (ADT) with docetaxel (D) and/or antiandrogen receptor therapies (ARTs) are the standard therapies in metastatic hormone-sensitive prostate cancer (mHSPC). Alterations in the tumor suppressor genes (TSGs) RB1, PTEN, and TP53 are associated with an aggressive evolution and treatment resistance in castration-resistant prostate cancer (CRPC).
To study the clinical implications of TSG mRNA expression in mHSPC patients.
This is a multicenter retrospective biomarker study in mHSPC patients. TSGlow status was defined when two or more out of the three TSGs presented low RNA expression by nCounter in formalin-fixed paraffin-embedded samples and TSGwt for the remaining cases. The microarray data from the CHAARTED trial were analyzed as an independent validation cohort.
Molecular data were correlated with CRPC-free survival (CRPC-FS) and overall survival (OS) by the Kaplan-Meier method and multivariate Cox analysis.
A total of 226 patients were included, of whom 218 were eligible: 93 were treated with ADT and 125 with ADT + D; 75.7% presented de novo stage IV and 67.9% high-volume disease. TSGlow (19.2%) was independently correlated with shorter CRPC-FS (hazard ratio [HR] 1.8, p = 0.002) and OS (HR 2, p = 0.002). In the CHAARTED trial, TSGlow was independently correlated with lower CRPC-FS (HR 2.2, p = 0.02); no differences in clinical outcomes according to treatment were observed in TSGlow patients, while a significant benefit was observed for ADT + D in the TSGwt group for CRPC-FS (HR 0.4, p < 0.001) and OS (HR 0.4, p = 0.001). However, no interaction was observed between TSG signature and treatment in either series. Study limitations are the retrospective design, small sample size, and lack of inclusion of patients treated with ADT + ART.
TSGlow expression correlates with adverse outcomes in patients with mHSPC. The investigation of new therapeutic strategies in these patients is warranted.
The low RNA expression of tumor suppressor genes in the tumors is correlated with adverse outcomes in patients with metastatic hormone-sensitive prostate cancer.
European urology oncology. 2024 Mar 01 [Epub ahead of print]
Natalia Jiménez, Marta Garcia de Herreros, Òscar Reig, Mercedes Marín-Aguilera, Caterina Aversa, Laura Ferrer-Mileo, Samuel García-Esteve, Leonardo Rodríguez-Carunchio, Isabel Trias, Albert Font, Alejo Rodriguez-Vida, Miguel Ángel Climent, Sara Cros, Isabel Chirivella, Montserrat Domènech, Mariona Figols, Joan Carles, Cristina Suárez, Daniel Herrero Rivera, Enrique González-Billalabeitia, Claudia Cívico, Núria Sala-González, Vicenç Ruiz de Porras, Maria J Ribal, Aleix Prat, Begoña Mellado
Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain., Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Department of Pathology, Hospital Clínic, Barcelona, Spain., Medical Oncology Department, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain., Medical Oncology Department, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Hospital del Mar, Barcelona, Spain., Medical Oncology Service, Instituto Valenciano de Oncología (IVO), Valencia, Spain., Medical Oncology Department, Hospital General de Granollers, Barcelona, Spain., Oncology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain., Medical Oncology Department, Fundació Althaia, Xarxa Assistencial Universitària de Manresa, Spain., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain., Medical Oncology Department, University Hospital, 12 de Octubre, Madrid, Spain., Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, IMIB-Universidad de Murcia, Murcia, Spain., Department of Medical Oncology, Institut Català d'Oncologia, Girona, Spain., Badalona Applied Research Group in Oncology (B-ARGO), Institut Català d'Oncologia - Germans Trias i Pujol Research Institute, Badalona, Spain., Department of Urology, Hospital Clínic, Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain., Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain; Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: .