What is the effect on Quality of Life as measured by validated questionnaires due to androgen ablation (deprivation or blockade) treatment in metastatic disease?
Seven randomised controlled trials comparing different hormone therapies and including patients with metastatic disease examined quality of life outcomes using validated questionnaires. The questionnaires used were the SWOG QLQ and SF-36 instruments (one trial) and the health-related QLQ instrument published by Cleary et al(six trials). None of these directly assessed the impact of hormone symptoms such as gynaecomastia and hot flushes on quality of life.
Overall the evidence was limited, with variations in the types of ADTs employed (albeit often featuring bicalutamide as the anti-androgen), numbers of domains assessed and reported, albeit with a degree of overlapping commonality, and the way in which quality-of-life changes were reported and analysed. Quality of life was not a primary outcome in virtually all of these studies. The majority of studies have an association with industry, particularly Zeneca/AstraZeneca. Their influence is impossible to ascertain. All were of low quality, with only two studies blinded and over 20% attrition in most studies.
Quality of life studies in the metastatic setting, given the presence of active cancer and managing cancer complications, have a different risk–benefit ratio versus quality of life studies in an adjuvant context. In these studies, few quality of life domains differed significantly with different hormone therapies. Studies comparing anti-androgen versus castration give an overall impression that sexual function was less affected than by castration, which makes biological sense but must be balanced by improvements in cancer control.
Combined androgen blockade with flutamide, when compared with orchidectomy alone, was associated with significantly more diarrhoea but better mental health scores in the first six months. As part of maximal androgen blockade treatments, flutamide when compared with bicalutamide had better physical capacity outcomes.
As cyproterone acetate is not recommended as first-line ADT either as monotherapy or in combination, and non-steroidal anti-androgens such as bicalutamide are not recommended or approved by the PBS as monotherapy, only the results dealing with combined androgen blockade for metastatic disease are applicable.
As stated above, the unknown extent and influence of industry in so many studies increases the difficulty in making objective evaluations.
Since all the quality of life studies examined report overall group findings, they should be regarded in a general sense when supporting individual patients in their treatment choices. This relates in particular to the timing of the commencement of androgen deprivation because of an absence of a clear and significant overall survival benefit with early versus later introduction of ADT.
Evidence summary and recommendations
| Using validated quality of life assessment questionnaires:
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|Toxicities in the context of what is important to each individual patient should be considered, as decrements in highly valued faculties for some patients may have a significant impact on the quality of life and overall adjustment of those individuals and those close to them.||C|
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