Benign Prostatic Hyperplasia BPH 26 Juli 2012 1

Benign Prostatic Hyperplasia (BPH) 26 Juli 2012

1. Kaplan, S. A. Identification of the patient with enlarged prostate: diagnosis and guidelines for management. Osteopathic Medicine and Primary Care 2007, 1: 11. 2. U Chong Lai, Yuk Tsan Wun, Tze Chao Luo & Sai Meng Pang. In a free healthcare system, why do men not consult for lower urinary tract symptoms (LUTS)? Asia Pacific Family Medicine 2011, 10: 7. 3. Edwards, J. E. , & Moore, R. A. Finasteride in the treatment of clinical benign prostatic hyperplasia: A systematic review of randomised trials. BMC Urology 2002, 2: 14

Kaplan, S. A. Identification of the patient with enlarged prostate: diagnosis and guidelines for management. EP (Enlarged Prostate): • Gejala? terapi simptomatik BAK dgn α-blocker. • Perjalanan penyakit yg memburuk menjadi AUR (Acute Urinary Retention)? terapi yg menyusutkan sel epitel prostat dgn 5α-reductase inhibitor (5 ARI)

• Indikator perjalanan penyakit yg memburuk: LUTS meningkat, ukuran prostat meningkat, kecepatan aliran urin menurun, komplikasi kandung kemih, hematuria dan resiko AUR meningkat. • Pencegahan AUR lebih baik karena prostatektomi atau insersi kateter menurunkan Qo. L, meningkatkan morbiditas & mortalitas.

Gejala 2 yg mengganggu • Obati gejala (α-blocker/ anti-cholinergik) • Pemantauan ketat Tanpa EP • Beri nasihat ttg gaya hidup, periksa pengobatan, besarkan hati. • Rubah perjalan penyakit (5 ARIs, terapi kombinasi) • Obati gejala • Beri nasihat ttg gaya EP hidup, periksa pengobatan, tenteramkan hati • Rubah perjalan penyakit (5 ARIs) pd orang Res. Ti tertentu • Pemantauan ketat Tanpa gejala 2 yg mengganggu

Dx BPH: • LUTS (Lower Urinary Tract Symptoms): freq, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying & urgency Ringan (skor = 1 -7), Sedang (skor = 8 -19); Berat (skor = 20 -35) • DRE (Digital Rectal Examination): diameter > 2 lebar jari prostate volume > 30 m. L • PSA (Prostate-specific antigen) > 1. 5 ng/m. L

• 1 ng = 0. 000001 mg = 0. 00001 gr

Peran Dokter Keluarga • • EP > 50% pada pria antara 50 -60 th. DK memulai diskusi tentang LUTS*. DK melakukan DRE untuk menentukan EP. DK meresepkan α-blockers kalau ada gejala yang mengganggu dan/atau 5α-reductase inhibitors (5 ARIs) kalau ada EP. *)U Chong Lai, Yuk Tsan Wun, Tze Chao Luo & Sai Meng Pang. In a free healthcare system, why do men not consult for lower urinary tract symptoms (LUTS)? Asia Pacific Family Medicine 2011, 10: 7.

Menunda konsultasi LUTS • Dianggap gejala penuaan biasa • Malu, takut • Tidak spesifik EP DDx

DDx LUTS: • Urologic and nonurologic : Prostate cancer, Prostatitis, Bladder cancer, Bladder stones, Overactive bladder, Interstitial cystitis, DM, Parkinson's disease, Congestive heart failure, Lumbosacral disc disease, Multiple sclerosis, Spinal cord injury, Stroke • Obat: Tricylic antidepressants, Anticholinergic agents, Diuretics, Narcotics, First-generation antihistamines, Decongestants • Obesitas, merokok, miras, hipertensi.

Peripheral zone (PZ) Up to 70% in young men The sub-capsular portion of the posterior aspect of the prostate gland that surrounds the distal urethra. It is from this portion of the gland that ~70– 80% of prostatic cancers originate. [16][17] Central zone (CZ) Approximately 25% normally This zone surrounds the ejaculatory ducts. The central zone accounts for roughly 2. 5% of prostate cancers although these cancers tend to be more aggressive and more likely to invade the seminal vesicles. [18 Transition zone (TZ) 5% at puberty ~10– 20% of prostate cancers originate in this zone. The transition zone surrounds the proximal urethra and is the region of the prostate gland that grows throughout life and is responsible for the disease of benign prostatic enlargement. (2)[16][17] Anterior fibro-muscular zone (or stroma) Approximately 5% This zone is usually devoid of glandular components, and composed only, as its name suggests, of muscle and fibrous tissue.

Penatalaksanaan BPH • Obat: α-blocker atau/dan 5 ARI • Prosedur invasif minimal (Rawat Jalan): TUNA: Transurethral Needle Ablation TUMT: Transurethral Microwave Thermotherapy + Stent prostat sementara • TURP/TUR (Rawat Inap): Transurethral resection of the prostate.

Daftar Obat PT Askes • 5α-reductase inhibitor: Dutasteride (Avodart): 1 dd Caps mg 0. 5 • α-blocker: Terazosin HCl (Hytrin, Hytroz) - 1 dd Tab mg 1 -2 Doxasozin Mesylate (Cardura) - 1 dd Tab mg 1 -2 Tamsulosine (Harnal) - 1 dd Tab mg 0. 2/04

Edwards, J. E. , & Moore, R. A. Finasteride in the treatment of clinical benign prostatic hyperplasia: A systematic review of randomised trials. BMC Urology 2002, 2: 14 Contoh Finasteride: 1 dd 1 Tab mg 5 • Finaxal (Sandoz): • Finpro (Interbat) • Proscar (Merck Sharp & Dohme) • Prostacom (Combiphar) • Reprostom (Fahrenheit)

Finasteride & Dutasteride = 5 α-reductase inhibitor (5 ARI) sintetis 5 ARI = suatu inhibitor dari enzyme yg mengkonversi testosterone ke DHT. Dihydrotestosterone (DHT), atau 5α-dihydrotestosterone (5α-DHT) = hormon androgen/sex steroid. Enzyme 5 α-reductase mensintesis DHT di prostat, testis, folikel rambut dan kelenjar adrenalis

• Indikasi: pengobatan BPH dan MPB (Male Pattern Baldness)

Tujuan Penelitian: menentukan eficacy & efek samping Finasteride melalui telaah pustaka & meta-analisis. Pustaka yg dicari: uji-coba finasteride yang randomised dan double-blind utk BPH hyperplasia. • Kata Kunci yg digunakan: 'finasteride', 'proscar', 'clinical trial', & 'benign prostatic hyperplasia' Dicari di/melalui: Pub. Med, the Cochrane Library, dan daftar rujukan laporan dan review.

Randomized & Double Blind Trial: X = Finasteride O = symptom score, urinary flow rate, volume prostat, putus berobat & efek samping Analisis: • RR • NNT atau NNH • Sensitivity analyses utk menilai pengaruh kegawatan simptom awal, volume prostat awal, uji-coba utama dan intervensi sebelumnya.

Hasil: (3 uji-coba dng kontrol aktif dan 19 dgn kontrol placebo). Uji-coba dgn placebo: 8820 pasien finasteride 5 mg & 5909 pasien placebo selama 3– 48 bln. • Finasteride: a. Setelah 48 bln - peningkatan lebih besar dlm hal total symptom score, maximum urinary flow rate, & vol prostate. b. Pd 12 bln – lebih banyak disfungsi sexual, impotensi, gg eyakulasi & penurunan libido. NNH disfungsi sexual pd 12 bln = 14. c. Pd 24 atau 48 bln: lebih sedikit AUR atau operasi; NNT pd 12 bln = 49 (31 -112) utk mencegah 1 AUR dan = 31 (2161) uk mencegah 1 operasi. d. Analisis sensitivitas menunjukkan manfaat finasteride mg 5 konstan, tidak dipengaruhi volume awal prostat.

Kesimpulan: • penelitian bermutu dengan N besar menunjukkan manfaat Finasteride dalam hal symptoms, flow rate & volume prostate. • Diperlukan lebih banyak penelitian dengan O dikotomi. Kesimpulan Valid?

Penilaian mutu uji-coba: • Setiap laporan penelitian yg dapat dianggap sbg randomised controlled trial dibaca masing 2 peneliti dan diberi Jadad Score. • Ketidak-sepakatan didiskusikan sampai ada kesepakatan. • Penelitian yg diikutsertakan jika skor max 5 dan skor min 2

Jadad Score Calculation Item 1 Was the study described as randomized? 2 Was the study described as double blind? Score 0/1 3 Was the study described as double blind? 0/1 4 Was the method of double blinding described & appropriate ? 5 Was there a description of withdrawals and dropouts? 0/1 6 Deduct one point if the method used to generate the sequence of randomization was inappropriate. 7 Deduct one point if the method of blinding was inappropriate. 0/-1

Outcome (O): Divalidasi dengan 2 urologist & 3 GP dgn minat urologi untuk menentukan O berdasarkan pendapat peneliti atau pasien. Informasi yg digali: 1. N finasteride & N placebo 2. symptom score (total, obstructive, mengganggu) 3. volume prostat 4. urinary flow rate (maximum, mean) 5. berhenti (total berhenti, berhenti krn tidak efikasius/efek samping) 6. efek samping: AUR dan operasi prostat. 7. PSA) 8. Volume sisa 9. Volume total yg dikeluarkan.

• Yang dicatat nilai absolut dan/atau mean/median (SD) pada titik 2 waktu: baseline dan 3, 6, 12, 18, 24, 36 & 48 bln pengobatan