ANDROGEN DEPRIVATION THERAPHY ON PRASTATE CA

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 Terapi hormonal EBRT + terapi hormonal Terapi investigasional ERBT + terapi hormonal (2-3 tahun) Terapi hormonal Prostatektomi radikal + diseksi KGB pelvis Terapi investigasional ERBT + terapi hormonal (2-3 tahun) Prostatektomi radikal + diseksi KGB pelvis Terapi investigasional Terapi hormonal Sangat tinggi: T: 4 atau Gleason : ≥8 atau PSA: >20 dan Temuan biopsi : limfovaskuler, neuroendokrin Terapi hormonal ERBT + terapi hormonal Terapi investigasional Terapi hormonal ERBT + terapi hormonal Sistemik terapi non hormonal (kemoterapi) ERBT + terapi hormonal Terapi hormonal Terapi sistemik dan terapi hormonal 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 I ntermiten Time to Start : Immediate and Deferred

6. MECHANISMS OF ANDROGEN AXIS BLOCKADE Inhibition of LH-RH and/or LH release Ablation of androgen sources Inhibition androgen synthesis 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 B ind 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 - B icalutamide 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 I nhibition of a very proximal step in adrenal function, aminoglutethimide blocks production of aldosterone and cortisol Medical Version of Adrenalectomy Ketoconazole D emonstrated loss of adrenal steroid synthesis and testosterone synthesis by Leydig ce lls

13. MEDICAL VS. SURGICAL ADT :

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

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