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

Abstract

PurposeThe 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).MethodsWe 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.ResultsWe 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.ConclusionFor 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.

Treatment-Related Cognitive Impairment in Patients with Prostate Cancer: Patients’ Real-World Insights for Optimizing Outcomes

“…HCP participants indicated that their patients appreciate this approach, though they clarified that most HCPs are not embracing intermittent treatment or de-escalation strategies, despite being recommended in clinical guidelines. They explained that this lack of IADT implementation may be due to the relative novelty of clinical data and the increased burden on HCPs having to learn yet another treatment protocol, both of which are reasons supported by previous literature [ 31 , 54 ].…”

Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men

“…Real-World IADT Utilization Systematic reviews comparing IADT and CADT demonstrate no difference in progression-free, PC- specific, or overall survival, particularly for nonmetastatic PC. 6,7,21 Despite this, guidelines vary in their recommendations for IADT. The American Urological Association and National Comprehensive Cancer NetworkÒ guidelines suggest IADT may be offered for patients with biochemical failure without metastases, and the European Association of Urology considers IADT for asymptomatic metastatic patients.…”

“…Although the rationale for IADT includes re-sensitizing the tumor and prolonging survival to castration resistance, the primary benefits are: potential quality of life improvement, reduced adverse effects, and lower treatment cost. 5–7 However, the evidence surrounding its benefits has not been conclusive, 8–11 and concerns remain regarding the trial definitions of noninferiority and their selection criteria. Consequently, guidelines vary in their recommendations for IADT and have not fully adopted this practice.…”

Guidance for the assessment and management of prostate cancer treatment-induced bone loss. A consensus position statement from an expert group

“…These indications are based upon clear evidence from large randomised clinical trials [10] , [11] , [12] , [13] . ADT may also be administered intermittently [14] .…”