BPH Diagnosis and Medical Treatment

BPH 85yr : 90% The most common disease of aging men Present in majority of men Prevalence : 60yr : 50%↑ 85yr : 90% Wide variance in symptoms Large prostate does not equal voiding problems

LUTS Morbidity & Complication of BPH Mortality of BPH : Rare LUTS : Bothersome Highly variable Treatment : Patient’s perception Degree of interfering life style

Definitions and Terminology BPH : Stromal and epithelial hyperplasia in periuretheral zone LUTS : Lower urinary tract symptoms The relationship of BPH & LUTS : Complex LUTS or LUTS suggestive of BPH >> prostatism BPH : Bothersome LUTS by histological BPH or increased tone of the prostate

LUTS Irritative versus Obstructive Irritative Obstructed Frequency/urgency/nocturia Obstructed Slow stream/stranguria/start-stop Difficult to distinguish by history alone since symptoms overlap

AUA/IPSS Sx Index, Bother Initial Evaluation History DRE & Focused PE UA PSA in select patients AUA/IPSS Sx Index, Bother

Medical History Surgery, general health Voiding History: polyuria, stranguria, frequency, urgency post void dribbling Voiding diary (nocturia) Urinary Infections :culture Incontinence

Physical Examination DRE Neurologic exam Mental status Ambulatory status Neuromuscular function Anal sphincter tone

Urinalysis Bladder cancer, CIS UTI, Urethral stricture Urethral, bladder stones

PSA Screening for cancer 10 year life expectancy and for whom the presence of cancer would change management One predictor of natural Hx of BPH

Optional Initial Test Urine Cytology : Bladder Ca, CIS Predominantly irritative Sx Smoking or other risk factors Serum Creatinine : Not recommended Renal insufficiency : 1%↓ Not more common than general population Non BPH cause as diabetic nephropathy

Symptom Assessment Sx alter QOL Sx quantification Severity of disease Response of therapy Sx progression 0~7 : mild 8~19 : moderate 20~35 : severe Not a replacement for personal discussion of Sx with the patient

Symptom Assessment IPSS : Recommended Other validated assessment : optional Frequency and severity of LUTS Bother score Interference with daily activities Urinary incontinence Sexual function Health related – QOL ICS Questionnaire, DPSS, BPH impact index, IPSS QOL, Sexual function Questionnaire

QOL

Optional Diagnostic Test Uroflometry measures rate of urine flow Not a first line test Post-void residual urine (PVR) useful tool for evaluation and treatment Non-prostatic case of Sx Selection of invasive Tx Prior failed BPH Tx Quantitative method to diagnose and follow result of treatment

Qmax : rate of urine flow Predict the response to surgery Predict the natural Hx of BPH Advantages LUTS with Normal Qmax : non prostatic cause Qmax < 10ml/sec : obstruction Disadvantages Sx response is not dependent on Qmax Test / retest variability, lack of well designed study → Not feasible to establish cut-point

PVR Optional Bladder dysfunction Identifies favorable response to Treatment Progression of disease Clinical tool not a singular diagnostic test Test / retest variability Lack of outcome studies No PVR cut-point Optional Doesn’t predict the response to medical Tx Elevated PVR without UTI, renal insufficiency, bothersome Sx - No level of RU mandates invasive Tx

Optional Diagnostic Tests Who Choose Invasive Tx Pr-flow study Qmax > 10ml/sec & surgery considered Prior failed surgery Neurologic disease Not indicated to predict response to medical Tx Cystoscopy : Hematuria, urethral stricture r/o Bladder Ca, prior surgery TRUS : Size & shape, selection of surgery

CMG, IVP, USG of Kidney Not recommended Indicated in Hematuria, UTI Renal insufficiency, stone Hx, upper tract surgery Hx

Initial Management and Discussion of Treatment Options Watchful waiting Medical therapy – pills Minimally invasive surgery Surgery

Treatment Watchful waiting Increase water intake↓ Mild Symptoms Mod or severe Symptoms without Renal insufficiency, UTI, retention Increase water intake↓ Decrease alcohol↓, Caffeine↓ SODA DRE, PSA : suggests natural Hx of Sx flow rate, AUR, surgery

Medical Treatment Options Alpha-adrenergic blockers 5 alpha-reductase inhibitors Combination therapies Phytotherapy

Alpha-adrenergic Blockers Opens prostatic urethra by relaxing smooth muscle in prostate Doxazosin, terazosin, flomax, uroxatrol and rapaflo Equal effectiveness Differences in adverse events LUTS secondary to BPH Very effective in relieving symptoms of BPH

Alpha-adrenergic Blockers Side Effects: postural hypotension, retrograde ejaculation Hypertension and cardiac risk factors LUTS – Alpha blocker only: incidence of CHF Patients with hypertension : separate management of hypertension May make cataract surgery difficult (floppy iris syndrome)

5 Alpha-reductase Inhibitors Reduces prostate volume 25-28% Reducing volume doesn’t always relieve obstruction Symptomatic prostatic enlargement treatment helps to prevent progression of disease (AUR, surgery) Sexual dysfunction, long-term Tx Not appropriate for men with LUTS without prostatic enlargement

Natural History of BPH PLESS study 1. 3,040 clinical BPH patients 2. IPSS: moderate to severe 3. Qmax: <15 ml/s 4. DRE: enlarged prostate gland 5. PSA <10 ng/ml (PSA 4-9.9: negative biopsy) 6. Follow-up: 4 years 약 4년전부터 보고되기 시작한 PLESS study는 비록 위약 대조 임상 시험이지만 전립선비대증의 자연사에 대한 유용한 정보를 제공하였습니다. PLESS study의 결과 중 일부를 간추려 말씀드리도록 하겠습니다. PLESS study는 임상증상이 있는 3040명의 환자를 대상으로 4년간 장기추적한 study입니다. 환자군은 IPSS가 8점이상이고, Qmax는 15미만이면서 PSA는 10미만으로 전립선암의 증거가 없고 DRE상 전립선의 용적이 크다고 생각되는 환자들이었습니다.

Natural History of BPH Risk of Acute Urinary Retention or Surgery 다음의 그림들은 initial PSA의 수치에 따른 acute urinary retention이나 BPH로 인한 수술의 위험도를 Kaplan-Meier curve로 보여주고 있습니다. 그림에서 알 수 있듯이 PSA 수치가 낮을수록 acute urinary retention이나 BPH로 인한 수술의 위험도는 적은 것을 알 수 있습니다. 특히 finasteride는 initial PSA 수치가 높을수록 acute urinary retention이나 BPH로 인한 수술의 위험도를 감소시키는 효과가 더 큰 것을 알 수 있습니다. 참고적으로 말씀드리면 finasteride는 PSA 수치가 0-1.3인 경우 43%, PSA 수치가 1.4-3.2인 경우 46%, PSA 수치가 3.2이상인 경우 60%의 acute urinary retention이나 BPH로 인한 수술의 위험도 감소를 보여주었습니다.

Natural History of BPH Change of Symptom Score 다음의 그림들은 initial PSA의 수치와 prostate volume에 따른 증상점수의 변화를 보여주고 있습니다. 그림에서 알 수 있듯이 PSA 수치가 낮을수록 placebo에 대한 효과가 커서 증상점수가 많이 호전되며 PSA수치가 3.3 이상인 경우 결국 4년 뒤에는 초기의 증상 정도로 환원된다는 것을 알 수 있습니다. 또한 prostate volume이 작을수록 placebo에 대한 효과가 커서 증상점수가 많이 호전되며 prostate volume이 클수록 증상점수의 호전이 적은 것을 알 수 있습니다.

Natural History of BPH Change of Peak Urinary Flow Rate 다음의 그림들은 initial PSA의 수치와 prostate volume에 따른 Qmax의 변화를 보여주고 있습니다. 그림에서 알 수 있듯이 PSA 수치가 낮을수록 placebo에 대한 효과가 커서 Qmax의 호전정도가 크며 PSA수치가 3.3 이상인 경우 결국 4년 뒤에는 초기의 증상보다 더 낮은 urine flow를 갖게 됩니다. 또한 prostate volume이 작을수록 placebo에 대한 효과가 커서 Qmax가 많이 호전되며 prostate volume이 클수록 Qmax는 점차 증가하다가 감소하는 경향을 보이게 됩니다.

Surgery Minimally Invasive (office) Surgery (operating room) Microwave TUNA Interstitial Laser Surgery (operating room) TURP HOLAP HOLEP

Surgery Patient selection determines type of procedure offered Surgery very effective in properly selected patients Majority of patients stop medications Absolute indications Retention Recurrent infections Bleeding Stones

Surgery Absolute Indications Relative indications Retention Repeated infection Bladder stones Relative indications Worsening symptoms Rising urine retention Desire to stop medication

Surgery Minimally invasive surgery Better symptom results than medication Minimal recovery – days Low incidence of long-term side effects No incontinence after treatment Higher future retreatment rates than surgery Not effective for patients in urine retention Excellent alternative to medication

Surgery OR based surgery Most effective means of relieving prostate obstruction Requires general/spinal anesthesia Removal of prostate tissue Variety of energies used to remove tissue Requires catheters after treatment Usually involves hospitalization

Surgery Indicated for urine retention Highest side effects Possible incontinence Retrograde ejaculation Best treatment outcomes Improves flow rate Lowers voiding symptoms

Recommendations Goal directed therapy Most patients have a variety of treatment options Medical management works well for most patients with minimal side effects Modern procedures are effective and safe Informed patient decision making : benefits, risks, costs