ANDROGEN DEPRIVATION THERAPHY

1. ANDROGEN DEPRIVATION
THERAPHY
Eko Indra P

2. INTRODUCTION
• Androgen deprivation therapy (ADT), also called androgen
suppression therapy, is an antihormone therapy whose main use
in treating prostate cancer
• ADT reduces the level of androgen hormones, to prevent the
prostate cancer cells from growing

3. INDICATION
• High risk and Very High Risk Prostate Cancer
• Metastatic Prostate Cancer
• In recurrence after RT or Surgery
• Most patients with T3 are, at the present
time, treated with neoadjuvant hormonal
therapy followed by RT

4. Risiko Usia
>80 tahun 71-80 tahun ≤ 70 tahun
Tinggi :
•T: 2b, 3a, 3b atau
•Gleason : ≥4+3 atau
•PSA: 10-20 atau
•Temuan biopsi :
>50% perineural,
duktal
1. Terapi hormonal
2. EBRT + terapi
hormonal
3. Terapi
investigasional
1. ERBT + terapi
hormonal (2-3
tahun)
2. Terapi hormonal
3. Prostatektomi
radikal + diseksi
KGB pelvis
4. Terapi
investigasional
1. ERBT + terapi
hormonal (2-3
tahun)
2. Prostatektomi
radikal + diseksi
KGB pelvis
3. Terapi
investigasional
4. Terapi hormonal
Sangat tinggi:
•T: 4 atau
•Gleason : ≥8 atau
•PSA: >20 dan
•Temuan biopsi :
limfovaskuler,
neuroendokrin
1. Terapi hormonal
2. ERBT + terapi
hormonal
3. Terapi
investigasional
1. Terapi hormonal
2. ERBT + terapi
hormonal
3. Sistemik terapi
non hormonal
(kemoterapi)
1. ERBT + terapi
hormonal
2. Terapi hormonal
3. Terapi sistemik
dan terapi
hormonal
4. Terapi multimodal
investigasional
Tabel 1. Penatalaksanaan kanker terlokalisir atau locally advanced.1

5. ANDROGEN DEPRIVATION THERAPY
• Androgen Deprivation Therapy :
– Medical
– Surgical (Orchidectomy) ; Simple or Subcapsullar
• The goal is Castration ; testosteron < 50ng/dl
• Strategy :
– Blokade :
• Complete Androgen Blokade (CAB) ; LHRH Agonist+ AA
• Single Androgen Blokade
– Timing : Continuous and Intermiten
– Time to Start : Immediate and Deferred

6. MECHANISMS OF ANDROGEN
AXIS BLOCKADE
1. Inhibition of LH-RH and/or LH release
2. Ablation of androgen sources
3. Inhibition androgen synthesis
4. Anti androgens
Bultitude MF. Campbell‐Walsh Urology
Tenth Edition. Bju International.
2012;109(3).

7. ANDROGEN PATHWAYS

8. 1. Inhibition of LH-RH and/or LH release
• LH-RH Agonists
- Desensitization of LH-RH receptors in the anterior
pituitary after chronic exposure to LH-RH, thereby
shutting down the production of LH and, ultimately,
testosterone decrease
- Cause Flare-up’ phenomenon
• LH-RH Antagonists
Bind immediately and competitively to the LH-RH
receptors in the pituitary, reducing LH concentrations
by 84% within 24 hours of administration

9. 2. Ablation of androgen sources
• Bilateral orchiectomy quickly reduces circulating
testosterone levels to less than 50 ng/dL
• Subcapsular Orchidectomy Bilateral (SOB)
advocated as a technique of ADT that avoids the
psychologic consequences of an empty scrotum
(Desmond et al, 1988)
• Quickest way to achieve castration level <12 hours

10. 3. Anti- androgens
• STEROID :
- Classic steroidal antiandrogen with direct AR blocking effects
- Rapidly lowers testosterone levels to 70% to 80% through its progestational
central inhibition
- Side effects are cardiovascular toxicity (4-40% for cyproterone acetate [CPA])
and hepatotoxicity.
• NON STEROID
- Blocking the testosterone feedback centrally
- libido, overall physical performance, and bone mineral density (BMD)
frequently preserved
- Bicalutamide showing a more favourable safety and tolerability profile than
flutamide and nilutamide

11. • Abiraterone
- Significantly decreases the intracellular testosteron level by
suppressing the synthesis at adrenal level and inside the
cancer cells
- Inhibits several cytochrome P pathways, as a potent,
selective and irreversible inhibitor of cytochrome P17, a
key enzyme in androgen synthesis
4. Inhibition androgen synthesis (2)

12. 4. Inhibiting androgen synthesis
• Aminoglutethimide
Inhibition of a very proximal step in adrenal function,
aminoglutethimide blocks production of aldosterone
and cortisol
Medical Version of Adrenalectomy
• Ketoconazole
Demonstrated loss of adrenal steroid synthesis and
testosterone synthesis by Leydig cells

13. MEDICAL VS. SURGICAL ADT :

14. Note :
ADT sistemik,
SOB hanya blok testosteron dari testis

15. Thank You