Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use.
To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients.
A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted.
The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated.
A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003).
Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials.
In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.
European urology oncology. 2023 Oct 12 [Epub ahead of print]
Nuria Romero-Laorden, David Lorente, Guillermo de Velasco, Rebeca Lozano, Bernardo Herrera, Javier Puente, Pedro P López, Ana Medina, Elena Almagro, Enrique Gonzalez-Billalabeitia, Jose Carlos Villla-Guzman, Aránzazu González-Del-Alba, Pablo Borrega, Nuria Laínez, Ana Fernández-Freire, Amaia Hernández, Alejo Rodriguez-Vida, Isabel Chirivella, Eva Fernandez-Parra, Fernando López-Campos, Maria Isabel Pacheco, Rafael Morales-Barrera, Ovidio Fernández, Rosa Villatoro, Raquel Luque, Susana Hernando, Daniel C Castellano, Elena Castro, David Olmos
Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain; Cátedra UAM-Fundación Instituto Roche de Medicina Personalizada de Precisión, Madrid, Spain., Medical Oncology Department, Hospital Provincial de Castellón, Castellón de la Plana, Spain., Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Biomarkers in Genito-Urinary Cancers Group, I+12 Biomedical Research Institute, Madrid, Spain., Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain., Urology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Genitourinary Cancers Traslational Research Unit, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain., Genomics and Therapeutics in Prostate Cancer Group, I+12 Biomedical Research Institute, Madrid, Spain., Fundación Centro Oncológico de Galicia, A Coruña, Spain., Hospital Universitario Quirón, Pozuelo de Alarcón, Spain., Hospital General Universitario de Ciudad Real, Ciudad Real, Spain., Department of Medical Oncology, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain., Hospital San Pedro de Alcántara, Cáceres, Spain., Department of Medical Oncology, Navarra University Hospital, Pamplona, Spain., Hospital Universitario Torrecárdenas, Almería, Spain., Medical Oncology Department, Gipuzkoa Cancer Unit, OSI Donostialdea - Onkologikoa Foundation, San Sebastián, Spain., Medical Oncology Department, Hospital del Mar, CIBERONC, IMIM Research Institute, Barcelona, Spain., Medical Oncology Department, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain., Hospital Universitario de Valme, Sevilla, Spain., Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain., Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain., Hospital Universitario Costa del Sol, Marbella, Spain., Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain., Fundación Hospital Alcorcón, Alcorcón, Spain., Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Translational Cancer Genetics Group, I+12 Biomedical Research Institute, Madrid, Spain., Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Genomics and Therapeutics in Prostate Cancer Group, I+12 Biomedical Research Institute, Madrid, Spain. Electronic address: .