Intermittent androgen deprivation therapy: recommendations to improve the management of patients with prostate cancer following the GRADE approach

Abstract

Xavier Bonfill,1–3 Ingrid Arevalo-Rodriguez,4,5 Laura Martínez García,3 Maria Jesús Quintana,1,2 Diana Buitrago-Garcia,4 Diego Lobos Urbina,6 José Antonio Cordero7 On behalf of the IADT Spanish Study Group 1Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2CIBER of Epidemiology and Public Health, Barcelona, Spain; 3Iberoamerican Cochrane Centre, Barcelona, Spain; 4Centro de Investigación en Salud Pública y Epidemiología Clínica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador; 5Hospital Ramon y Cajal (IRYCIS), Clinical Biostatistics Unit, CIBER of Epidemiology and Public Health, Madrid, Spain; 6Pontificia Universidad Católica de Chile, Santiago, Chile; 7School of Health Sciences Blanquerna – Ramon Llull University, Barcelona, Spain Purpose: The purpose of this study was to provide evidence-based recommendations of intermittent androgen deprivation therapy (IADT) compared with continuous androgen deprivation therapy (CADT) for men with prostate cancer (PCA). Methods: We conducted a comprehensive search in MEDLINE, EMBASE, The Cochrane Library, CINAHL, and ECONLIT, from the database inception to December 2017. We adhered to the Grading of Recommendations, Assessment, Development and Evaluation framework to assess the quality of the evidence and to formulate recommendations. Results: We included one systematic review with 15 trials as well as three additional studies that assessed IADT versus CADT, all of them focused on PCA patients in advanced stages. The findings did not show differences for critical and important outcomes, including adverse events. Trials reported the benefits of IADT in terms of selected domains of health-related quality of life, although with high heterogeneity. Evidence quality was considered moderate or low for most of the assessed outcomes. We identified a patient preference study reporting a high preference for IADT, due to issues related to quality of life, general well-being, and side effects, among others. We did not identify economic studies comparing these regimes. We formulate four recommendations: one no-recommendation, one conditional recommendation, and two good practice points. Conclusion: For men in early stages of PCA, it is not possible to make any recommendation about the preferable use of IADT or CADT due to the lack of available evidence. For men in advanced stages of the disease, an IADT should be considered as soon as clinically reasonable (weak recommendation and low certainty of the evidence). Clinicians should discuss the risks and benefits of IADT and CADT with their patients, taking into account their values and preferences. Keywords: hormone deprivation therapy, prostate cancer, prostate neoplasm, evidence-based medicine, GRADE approach

Keywords

• Androgen deprivation therapy
• hormonal deprivation therapy
• prostate cancer
• prostate neoplasm.