What is the effect on Quality of Life as measured by validated questionnaires due to androgen ablation (deprivation or blockade) treatment in metastatic disease?

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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[1](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.[2] As part of maximal androgen blockade treatments, flutamide when compared with bicalutamide had better physical capacity outcomes.[3]

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.

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Evidence summary and recommendations

Evidence summary Level References
Using validated quality of life assessment questionnaires:
  • for metastatic disease there was evidence that castration is associated with poorer sexual function when compared with non-steroidal anti-androgen monotherapy
  • combined androgen blockade with flutamide when compared with orchidectomy alone was associated with more diarrhoea but better mental health scores
  • as part of maximal androgen blockade treatments flutamide had better physical capacity outcomes than bicalutamide.
II [3], [4], [5], [6], [7], [8]
Evidence-based recommendationQuestion mark transparent.png Grade
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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References

  1. Cleary PD, Morrissey G, Oster G. Health-related quality of life in patients with advanced prostate cancer: a multinational perspective. Qual Life Res 1995 Jun;4(3):207-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7613531.
  2. Moinpour CM, Savage MJ, Troxel A, Lovato LC, Eisenberger M, Veith RW, et al. Quality of life in advanced prostate cancer: results of a randomized therapeutic trial. J Natl Cancer Inst 1998 Oct 21;90(20):1537-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9790546.
  3. 3.0 3.1 Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, et al. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology 1995 May;45(5):745-52 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7538237.
  4. Chodak G, Sharifi R, Kasimis B, Block NL, Macramalla E, Kennealey GT. Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma. Urology 1995 Dec;46(6):849-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7502428.
  5. Kaisary AV, Tyrrell CJ, Beacock C, Lunglmayr G, Debruyne F. A randomised comparison of monotherapy with Casodex 50 mg daily and castration in the treatment of metastatic prostate carcinoma. Casodex Study Group. Eur Urol 1995;28(3):215-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8536775.
  6. Tyrrell CJ, Kaisary AV, Iversen P, Anderson JB, Baert L, Tammela T, et al. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 1998;33(5):447-56 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9643663.
  7. Iversen P, Tveter K, Varenhorst E. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group. Scand J Urol Nephrol 1996 Apr;30(2):93-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8738052.
  8. Boccardo F, Rubagotti A, Barichello M, Battaglia M, Carmignani G, Comeri G, et al. Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study. J Clin Oncol 1999 Jul;17(7):2027-38 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10561254.

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Appendices