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

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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?

Effects on quality of life

Only three randomised controlled trials comparing different hormone therapies and including men with locally advanced non-metastatic disease examined quality of life outcomes using validated questionnaires.[1][2][3][4][5][6] One trial used the EORTC QLQ C-30 instrument with the prostate cancer supplementary module and the Depression Anxiety Stress Scales, and two trials used the healthrelated QLQ instrument published by Cleary et al.[7] The longest follow-up was only 12 months.[1][2][3][4] 58 None of the instruments used directly assessed the impact of ADT-related symptoms such gynaecomastia and hot flushes on quality of life.

Overall the evidence was limited. There were variations (albeit with a degree of overlapping commonality) in the types of ADTs employed, the instruments used and the numbers of domains assessed and reported. There were also variations in 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. All were of low quality, with attrition greater than 20% or unclear in two of the three studies.

Different risk and benefit analyses apply to men being treated with long-term adjuvant ADT for locally advanced disease and men being treated with ADT for metastatic disease. One study included patients with metastatic disease as well as locally advanced disease.

For non-metastatic disease there were two studies[1] [3] [4] one (supported by industry) compared bicalutamide with castration, and the other[2] (not supported by industry) compared two LHRH agonists with cyproterone acetate and clinical monitoring. Both studies showed that castration was associated with poorer sexual function than anti-androgen monotherapy. In the bicalutamide study, physical capacity as measured with the Cleary instrument was improved with bicalutamide, however, there were no significant differences in the other eight domains.

Only one study[2] [5] had patients randomised to a non-treatment arm in a clinical environment in which commencement of androgen deprivation was triggered increasingly by a raised PSA for patients not having treatment with curative intent. The numbers in this study are small but they reported a significant increase in emotional distress for the non-treatment arm (p = 0.002) with increased sexual dysfunction at one year for all three treatment arms, particularly for goserelin (p < 0.001).

In the adjuvant setting, long-term quality-of-life impacts related to therapy, when dealing with the ‘chance of having cancer’, present another paradigm. These studies reported radiotherapy adverse events rather than quality of life outcomes using validated instruments.

See also Intermittent or continuous ADT


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Evidence summary and recommendations

Evidence summary Level References
Using validated quality of life assessment questionnaires: For non-metastatic prostate cancer there was evidence that medical or surgical castration is associated with poorer sexual function when compared with non-steroidal anti-androgen monotherapy. II [1], [3], [4], [5], [2]

Since all 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 timing the commencement of androgen deprivation because of the absence of a clear and significant overall survival benefit with early versus later introduction of ADT.

Evidence-based recommendationQuestion mark transparent.png Grade
Toxicities should be considered in the context of what is important to each individual patient, as for some patients impairment of sexual function may have a significant impact on their quality of life and overall adjustment, as well as affecting adversely those close to them.
C


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References

  1. 1.0 1.1 1.2 1.3 Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, et al. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol 2000 Nov;164(5):1579-82 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11025708.
  2. 2.0 2.1 2.2 2.3 2.4 Green HJ, Pakenham KI, Headley BC, Yaxley J, Nicol DL, Mactaggart PN, et al. Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. BJU Int 2004 May;93(7):975-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15142146.
  3. 3.0 3.1 3.2 3.3 Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Baert L, Tammela T, et al. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years. Urology 1998 Mar;51(3):389-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9510340.
  4. 4.0 4.1 4.2 4.3 Iversen P. Quality of life issues relating to endocrine treatment options. Eur Urol 1999;36 Suppl 2:20-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10529562.
  5. 5.0 5.1 5.2 Green HJ, Pakenham KI, Headley BC, Gardiner RA. Coping and health-related quality of life in men with prostate cancer randomly assigned to hormonal medication or close monitoring. Psychooncology 2017 Nov 17;11(5):401-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12228873.
  6. 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.
  7. 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.

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Appendices