Improving Quality of Life (QoL) in Hormonal Therapy (ADT) Derek J. Rosario Senior Lecturer and Hon. Consultant Urological Surgeon Academic Urology Unit and Department of Urology Royal Hallamshire Hospital

Scope of this talk Historical view of ADT Mitigation of adverse events / impact on QoL Limiting exposure Pharmacological interventions Exercise interventions Dietary supplements/ complementary therapies

Scope of this talk Mitigation of adverse events Limiting exposure Pharmacological interventions Exercise interventions Dietary supplements/ complementary therapies

Charles Édouard Brown-Séquard (1817– 1894) Testosterone ‘Elixir’ of vitality Charles Édouard Brown-Séquard (1817– 1894)

Non-beneficial effects of Androgen withdrawal (ADT)

Impact of ADT on Generic QoL SF36 J Urol 191:964, 2014

Results Limitations Selection bias Primary ADT older at outset

Duration of Adjuvant ADT 630 men randomised to 18 months vs. 36 months adjuvant ADT EORTC QLQ 30 and PR25 72% adherence to completion of questionnaire 21 scales (15 on EORTC QLQ 30 and 9 on PR25) Nabid A et al. Long-term QoL in high-risk prostate cancer: Results of a phase III randomized trial. J Clin Oncol 32, 2014 (suppl 4; abstr 5).

Results (Nabid et al 2014) Statistically significant improvement in 6/21 scales Effect size (clinical relevance) greatest for sexual interest, functioning and hot flashes

Pharmacological interventions Nguyen PL doi: 10.1016/j.eururo.2014.07.010. [Epub ahead of print]

Problem Intervention Evidence QoL Impact Bone Health Gynaecomastia Hot flashes / flushes

Problem Intervention Evidence QoL Impact Bone Health Pamidronate Zoledronate Denosumab Toremifene Prevents decrease in BMD Increase in BMD Decrease in fracture risk Decreased fracture but increased DVT Gynaecomastia Hot flashes / flushes

Both reduce gynaecomastia significantly Problem Intervention Evidence QoL Impact Bone Health Gynaecomastia Breast irradiation Tamoxifen Both reduce gynaecomastia significantly Hot flashes / flushes

All reduce hot flashes but MP/ cyproterone more effective Problem Intervention Evidence QoL Impact Bone Health Gynaecomastia Hot flashes / flushes Venlafaxine medroxyprogesterone cyproterone All reduce hot flashes but MP/ cyproterone more effective

Problem Intervention Evidence QoL Impact Bone Health Pamidronate Zoledronate Denosumab Toremifene Prevents decrease in BMD Increase in BMD Decrease in fracture risk Decreased fracture but increased DVT ? Gynaecomastia Breast irradiation Tamoxifen Both reduce gynaecomastia significantly Hot flashes / flushes Venlafaxine medroxyprogesterone cyproterone All reduce hot flashes but MP/ cyproterone more effective

Exercise interventions

Objectives Rigorous systematic review and metaanalysis Effects of exercise interventions on Cancer-specific QoL Effects of exercise interventions on disease-progression Effects on cardiovascular health Adverse effects of exercise interventions

QoL and Fatigue

Disease-progression (PSA)

Improving QoL in ADT Adverse events common Reduce exposure to ADT Discuss with the patient before initiating treatment Reduce exposure to ADT Duration of adjuvant ADT Exercise interventions ? Supervised ? Adherence

Focus of Studies Better studies examining and reporting QoL Avoid narrow focus on Survival alone