LUTS ~ BPH (Benign Prostate Hyperplasia)
Dr. dr. Nur Rasyid SpU (K)
Departemen Urologi Urologi FKUI - RSCM
LUTS
BPH
n
Normal Size of the young adult is 15-20 cc.
• Pathological process start at age 40 years • 50% in men > 60 years* • 90% in men > 85 years* • 90% in men 50-80 years** • Second most frequent in urology in Indonesia *AUA practice guidelines committee. J.Urol.2003,170
BPH Prevalence
BPH
Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone McVary KT. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-803.
Patophysiology
BPH Symptoms Voiding (obstructive) Symptoms • • • • •
Hesitancy Weak stream Straining to pass urine Prolonged micturition Feeling of incomplete bladder emptying • Urinary retention
Storage (irritative or filling symptoms • • • •
Urgency Frequency Nocturia Urge incontinence
DR
BPH Symptoms
DIAGNOSTIC EVALUATION •
Medical History
•
Symptom score questionnaires
•
•
The International Prostate Symptom Score (IPSS)
•
Frequency volume charts and bladder diaries
Physical examination and digital-rectal examination •
Digital-rectal examination and prostate size evaluation
• Urinalysis, Prostate-specific antigen (PSA), PVR, uroflowmetry. •
etc
International Prostate Symptom Score (IPSS)
Score / Severity 0-7 Mild 8 - 19 Moderate 20 35 Severe
DRE & TRUS prostat
Digital-rectal examination
Method of Digital Rectal Examination (DRE)
TRUS prostat (transrectal ultrasonography)
COLOK DUBUR ~ Rectal Touche (RT) Yang terpenting •
•
Prostat keras, nodul, atau asimetri staging T (tumor) Curiga (+) pada RT dg PSA < 2ng/ml (+) Ca P = 5-30%
Uroflometry
Uroflowmetri Uroflowmetry disarankan untuk penegakan diagnosis awal dan harus dilakukan sebelum terapi
LE
GR
1b
A
Pemeriksaan PSA Bisa Meningkat pada : 1.BPH : Pembesaran Prostat Jinak 2.Prostatitis : Akut & Koronis 3. Kanker Prostat Total PSA : < 4ng/ml (Nilai Normal )
•
Untuk screening awal Kanker Prostat
•
Prediktor yang lebih baik daripada Colok Dubur & USG TransRectal (TRUS) •
Pemeriksaan PSA •
Total PSA< 4 ng/ml
•
Free PSA ( bila PSA 4-10)
•
–
Rasio Free/Total PSA ~ (+)CaP pada Biopsi
–
< 0,10
56%
–
> 0.25
8%
PSA velocity / percepatan peningkatan PSA _ –
Kurang bermanfaat untuk diagnosis CaP
–
monitoring pengobatan CaP
Diagnosis kanker prostat Indikasi biopsi: •
Kecurigaan pada pemeriksaan colok dubur
•
PSA > 4 ng/ml
•
PSA-D ( kadar PSA/volume prostat) > 0.15 bila kadar PSA antara 2 4 ng/ml. –
•
Peningkatan PSA : (>0.75-1.0 ng/dL/yr)
Who is at risk of BPH disease progression? Older age (> 60 years) Moderate-to-severe symptoms (IPSS > 8) Low urinary flow rate (Qmax <10.6mL / s) Enlarged prostate (PV > 30mL) Increased PSA level (≥ 1.5 ng/mL)
1. McConnell J et al. N Engl J Med . 2003;349:2387 –2398; 2. Emberton M et al. IJCP . 2008;62:1076 1086; 3. Emberton M et al. BJU Int. ‒
BPH Management: treatment Conservati ve
Medical treatment
MIST (Minimally invasive Surgical Therapy)
Surgical treatment
Watchful waiting
α1 adrenergic blocker
TUNA
Open prostatectomy
Dietary Modification
5-ARI
Thermotherapy
TUIP/TURP
Antimuscarinic
Urolift
TUVP
PDE-5 inhibitor Combination Phytotherapy
Laser Prostatectomy
Medical Treatment • IPSS > 7
Gratzke C. Eur Urol. 2015;67(6):1099-109.
Medical Treatment - Alpha blocker - Androgen suppression (5 ARIs) - PDE 5 Inhibitor - Combination Therapy - Phytotherapy
DR
BPH Medical Treatment Options
- blockers
α
• Mechanism of action: α1-blockers aim to inhibit the effect of endogenously released noradrenaline on smooth muscle cells in the prostate and thereby reduce prostate tone and BOO • Molecular studies have further identified three subtypes of the α1- AR(α1A, α1B, and α1D). • Their relative distribution and concentration in the prostate, bladder, neck, brain, and vascular smooth muscle have been exploited to develop uroselective α1-adrenergic antagonists and reduce side effects. Gratzke C. Eur Urol. 2015;67(6):1099-109.
Type of Alpha Adrenergic Receptor
α1A
α1B
α1D
Primary subtype expressed in the prostate. Regulates contraction of the smooth muscle in the prostate, bladder base and neck, urethra, seminal vesicles, and vas deferens.8-12
Primary subtype expressed in the blood vessels. Regulates contraction of arterial blood vessels in response to postural redistribution of blood volume.4-7
Primary subtype expressed in the bladder, spinal cord, and nasal passages. Thought to play a role in bladder symptoms and nasal secretions.1,6
1. Schwinn DA, . Int J Urol . 2008;15:193-199. 2. Kaplan SA Urology . 2004;63:428-434.
5. Carbone DJ, . Int J Impotence Res. 2003;15:299-306.
- blockers
α
Practical considerations: • Alpha1-blockers are often considered the first-line drug treatment of male LUTS because of their rapid onset of action, good efficacy, and low rate and severity of adverse events. • Doxazosin • Terazosin • Alfuzosin
Non Selective Alpha Blocker
• Tamsulosin • Silodosin
Selective Alpha Blocker
Silodosin is the newest selective alpha 1 Blocker Gratzke C. Eur Urol. 2015;67(6):1099-109
Pharmacolog ic S electivity Profiles of α1-Blocker
α1-Receptor
α 1
-Blockers
Selectivity
Doxazosin1
α1A =
α1D = α1B
Terazosin1
α1A =
α1D = α1B
α1A =
α1D = α1B α1D >α1B
Alfuzosin1
Tamsulosin1,2
α1A =
Silodosin3
α1A >α1D >α1B
Results based on in vitro data
1. Schwinn DA, et al. Mayo Clin Proc. 2004;79:1423-1434. 2. Kenny BA, et al. Br J Pharmacol. 1996;118:871-878.
Silodosin: High uroselectivity in Alpha 1A
Silodosin has extremely higher selectivity for a1A-AR compared with other a1AR –blockers (162 times)
% of patients with a simultaneous improvement in 3 of the most bothersome symptoms Statistically significant superiority vs tamsulosin on simultaneous improvement of frequency, nocturia and incomplete emptying (EU study - post hoc analysis)
5 ARI (5-alpha reductase inhibitors) • Prostate growth is stimulated by androgenic hormones, especially dihydrotestoster-one. • Finasteride and dutasteride inhibit the conversion of testosterone to dihydrotestosterone, suppressing prostate growth. • These agents appear to be most beneficial when the prostate volume is 40 mL or greater. • The 5-alpha reductase inhibitors do not provide immediate symptom relief, and approximately six months of therapy is required to achieve clinical benefit
5 ARI Practical considerations: • Treatment with 5-ARIs should be considered in men with moderate-to-severe LUTS and an enlarged prostate (> 40 mL) and/or elevated PSA concentration (> 1.4-1.6 ng/mL). Due to the slow onset of action, they are suitable only for long-term treatment (years). • Their effect on the serum PSA concentration needs to be considered for prostate cancer screening. Gratzke C. Eur Urol. 2015;67(6):1099-
α
- blocker vs 5 ARI
Lepor H. Rev Urol 2007; 9: 181-190; Tanguay S et al. Can Urol Assoc J 2009; 3: S92-S100
Algoritma Tata Laksana Pilihan Terapi Medikamentosa IAUI Guideline 2017 Pria diduga BPH dengan indikasi tatalaksana medikamentosa
Gejala yang mengganggu?
Tidak
Ya
Gejala storage yang paling dominan?
Tidak
Volume prostat > 30 ml?
Tidak
Ya
Tidak
Ya
Edukasi & modifikasi gaya hidup dengan/tanpa -blocker
Gejala storage residual Konservatif dengan/tanpa edukasi & modifikasi gaya hidup
Tambahkan Antagonis Reseptor Muskarinik
Poliuria nokturnal yang dominan?
Tidak
Ya
Tata laksana jangka panjang?
Ya
Edukasi & modifikasi gaya hidup dengan/tanpa 5 ARI 1-blocker /PDE5I *
Edukasi & modifikasi gaya hidup dengan/tanpa Antagonis Reseptor Muskarinik
Edukasi dan modifikasi gaya hidup
33
Surgery • Surgery is recommended for patients who have – – – – –
Renal insufficiency secondary to BPH, Recurrent urinary tract infections (UTIs), Gross hematuria due to BPH, or Bladder stones, LUTS refractory to other therapies.
• The presence of a bladder diverticulum is not an absolute indication surgery unless associated with recurrent UTI or progressive bladder dysfunction.
Take home message The successful management of patients with •LUTS associated with BPH should include assessments of QoL and monitoring of medication-related side effects • Alpha blocker gives fast and effective relief of bothersome symptoms •5ARI should give by indications •Individualized your patient’s treatment > Selective Alfa 1 Blocker
