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Management of ca prostate


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Management of ca prostate

  2. 2. Prostate Treatment Options
  3. 3. ADT in Low Risk Disease • Common practice in community • No survival benefit found after 15 years • Placing patients with early prostate cancer on ADT SHOULD NOT be of routine practice ( NCCN 2017 )
  4. 4. ADT in Intermediate Risk Disease • Addition of short term ADT to radiation therapy improved OS • EORTC 22991 : 6 months ADT improved biochemical DFS in intermediate risk group as compared to radiation alone
  5. 5. ADT in High Risk Disease • Long duration of ADT is preferred • Evidence from following trials is available - RTOG 9202 trial - EORTC 22863 trial - DART 01/05 trial - RTOG 8531
  6. 6. OG 9202 • Group 1 4 months ADT before and during RT • Group 2 4 months ADT before and during RT followed by 2 years of ADT • Subgroup : GS 8-10, OS benefit
  7. 7. EORTC 22863 trial • Node-negative patients with clinical stage T3 disease or T1–T2 patients with high- grade disease • Received adjuvant ADT on the first day of radiotherapy (prescribed dose of 70 Gy) and continued for 3 years. • The 10-year overall survival was 58% versus 40% for patients treated with ADT plus EBRT and EBRT alone, respectively (p = 0.0004).
  8. 8. PSA level at 7 months (SWOG 9346 cohort)• After starting ADT, the PSA level after 7 months of ADT may lead to 3 groups with very different survival expectancy. • The median survival is 75 months if the PSA level < 0.2 ng/mL, 44 months if the PSA < 4 ng/mL, 13 months if the PSA is > 4 ng/mL.
  9. 9. Enzalutamide • Enzalutamide is an AR signalling inhibitor that directly targets three stages of the AR signalling pathway. • The most common side effects of enzalutamide are fatigue, hypertension, and hot flushes. In <1% of patients on enzalutamide, seizures occurred.
  10. 10. Evidence : AFFIRM trial
  11. 11. Results
  12. 12. The androgen-signaling axis and its inhibitors. Testicular androgen synthesis is regulated by the gonadotropin-releasing hormone (GnRH)–LH axis, whereas adrenal androgen synthesis is regulated by the corticotrophin-releasing hormone (CRH)-ACTH axis. GnRH agonists and corticosteroids inhibit stimulation of the testes and adrenals, respectively. Abiraterone inhibits CYP17, a critical enzyme in androgen synthesis. Bicalutamide, flutamide, and nilutamide competitively inhibit the binding of androgens to androgen receptors; enzalutamide also blocks the translocation of the ligand bound AR complex to the nucleus and from binding to DNA. DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulphate; DHT, dihydrotestosterone; AR, androgen receptor; ARE, androgen-response element.
  13. 13. Enzalutamide : • A novel anti-androgen that blocks AR binding, nuclear translocation and transcription. • Enzalutamide is used as a once-daily oral treatment. • AFFIRM study in 2012 randomized 1,199 patients with metastatic CRPC in a 2/1 fashion between enzalutamide or placebo. (The patients had progressed after docetaxel treatment). • After a median follow-up of 14.4 months, the median survival in the enzalutamide group was 18.4 months compared to 13.6 months in the placebo arm (HR: 0.63, p < 0.001). This led to the recommendation that the study be halted and unblinded. • The benefit was observed irrespective of age, baseline pain intensity, and type of progression.
  14. 14. • CYP17 inhibitor. • It is used once daily combined with prednisone twice daily (10 mg/ day). • large phase III COU-AA-301 trial used a total of 1,195 patients with metastatic CRPC were randomised in a 1/1 fashion between abiraterone acetate or placebo, In patients with progressive disease after docetaxel therapy the median survival in the abiraterone group was 15.8 months compared to 11.2 months in the placebo arm (HR: 0.74, p < 0.001). • The benefit was observed irrespective of age, baseline pain intensity, and type of progression. • most common grade 3/4 side effects did not differ significantly but mineralocorticoid-related side effects were more frequent in the abiraterone group, mainly grade 1/2 (fluid retention, oedema or hypokalaemia). • As of today, the choice between third-line hormonal treatment (using enzalutamide or abiraterone) or second line chemotherapy (cabazitaxel) remains unclear with no clear decision-making findings published. Abiraterone Acetate
  15. 15. • Bone-seeking radiopharmaceuticals (samarium-153- EDTMP, strontium-89): Three radiopharmaceuticals are currently FDA-approved for the palliative treatment of painful bone metastases 1. phosphorus-32 2.strontium-89 3.samarium-153-EDTMP. Myelosuppression is the predominate toxicity associated with all of the bone seeking radioisotopes.
  16. 16. Relative contraindications • Severe urinary irritative/obstructive symptomatology • Extensive TURP defect • Substantial median lobe hyperplasia • Prostate dimensions larger than the grid (>60 mm in width & >50mm in height) • Severe pubic arch interference • Gross seminal vesicle involvement • Prior pelvic radiotherapy • Inflammatory bowel disease • Pathologic involvement of pelvic lymph nodes