Prostate Disease Chad Baxter, MD
Managing BPH and LUTS Chad Baxter, MD Department of Urology cbaxter@mednet.ucla.edu 33 nd Annual UCLA Intensive Course in Geriatric Medicine & Board Review
Prevalence of Histologic BPH 100 90 80 70 60 50 40 Prevalence, % 30 20 10 0 1 to 10 11 to 20 21 to 30 31 to 40 41 to 50 51 to 60 61 to 70 71 to 80 81 to 90+ Age (years) Be SJ, J Urol 1984
Acute Urinary Retention 2,115 men aged 40 to 79 from Olmsted Co, MN 40 35 30 25 20 15 10 5 0 Mild to Moderate Symptoms Moderate to Severe Symptoms 40 49 years old 70 79 years old Jacobsen SJ, J Urol 1997
Severity of Symptoms Over Time 30% 55% Remain Stable Improve Worsen 15%
Prostate Anatomy
Enlarged prostate on rectal exam does not equal obstruction
Terminology Benign Prostatic Hyperplasia (BPH): histologic diagnosis. Benign Prostatic Hypertrophy (BPH): anatomic Bladder Outlet Obstruction (BOO): functional assessment, intentionally vague (prostate, bladder neck, sphincter, stricture?)
Lower Urinary Tract Symptoms LUTS Structural or functional abnormality of LUT Bladder, Bladder Neck, Prostate, External Sphincter, Urethra May arise from central or peripheral nerve disease May be secondary to cardiovascular, respiratory, or renal disease
Lower Urinary Tract Symptoms LUTS Storage Symptoms (akin to diastolic dysfunction?) Voiding Symptoms (systolic dysfunction?) Post-micturition Symptoms
Lower Urinary Tract Symptoms LUTS Storage Symptoms Urgency Frequency Nocturia Urinary incontinence
Lower Urinary Tract Symptoms LUTS Voiding Symptoms Hesitancy Weak stream Straining Splitting or spraying Urinary retention
Lower Urinary Tract Symptoms LUTS Post-Micturition Post-micturition dribble Persistent urge Feeling of incomplete emptying
Basic Evaluation of LUTS History Include nature, duration LUTS Surgical history affecting GU tract Assess Symptoms and Bother Grade severity of LUTS International Prostate Symptom Score (IPSS), AUA Symptom Index (AUASI)
Basic Evaluation of LUTS Physical Exam Palpable bladder? Flank or upper quadrant abd mass, tenderness? DRE: sphincter tone, rectal mass, prostatic tenderness, pelvic floor/levator tone Urinalysis Serum PSA? Correlation with prostate volume, prostate cancer, prostatic irritation and recent ejaculation. Creatinine, GFR?
LUTS Bothersome Complicated LUTS Suspicious DRE; Retention; Hematuria; Renal Insufficiency; Pain; Infection; Neurological Disease Little or No Bother Reassurance and Follow-up Refer to Urology
Bothersome, UNcomplicated LUTS Predominant, Significant Nocturia Frequency Volume Chart Standard Treatment: Fluid and Food Intake Lifestyle Advice Bladder Training Pharmacotherapy Polyuria or Nocturnal Polyuria No Polyuria? Standard Treatment Failure? Specialized Mgmt
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. No prior GU surgery, trauma, instrumentation Normal UA, normal PSA Slightly enlarged (30g), benign prostate Bladder is not palpable No complicating symptoms
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. Consider formal, validated questionnaire AUA Symptom Index International Prostate Symptom Score Discuss fluid management Volume, Irritants Timing of fluid consumption (timing of diuretic)
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. He reports no longer drinking 6 cups of coffee, wine at 9pm dinner, or water overnight by his bedside. He is improved, but not enough to warrant eliminating coffee and wine. What next?
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. Discuss pharmacotherapy Alpha adrenergic receptor blockers 5 alpha reductase inhibitors Phosphodiesterase-5 inhibitors
Typical First Line Therapy: Alpha Blocker Alpha adrenergic receptor blockers Block sympathetic mediated contraction of prostatic smooth muscle and bladder neck Side effects: hypotension, nasal congestion Indication of physiologic efficacy: retrograde ejaculation
Alpha Blockers: Typical First Line Therapy Non-Selective (alpha 1A, 1B, 1D) Alfuzosin (Uroxatral) Doxazosin (Cardura) Terazosin (Hytrin) Selective (alpha 1A), but side effect profile not much better Tamsulosin (Flomax) Silodosin (Rapaflo)
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. You start him on tamsulosin 0.4 mg QHS
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. He returns at least one week later Side effects of dizziness and stuffy nose improved after the first few days Slight decrease in ejaculate volume He completes AUASI or IPSS questionnaire, reports 50% improved.
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. Increase tamsulosin to 0.8 mg QHS? Add or substitute with 5-alpha reductase inhibitor? Bothered by his partial retrograde ejaculation? Prostate enlarged enough to be candidate (30g)? Daily PDE-5 Inhibitor?
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. He selects 5-ARI
Typical Second-Line Therapy: 5- Alpha Reductase Inhibitors 5-ARI block conversion of testosterone to dihydrotestosterone (DHT) in the prostate DHT contributes to prostatic hypertrophy 5-ARIs shrink the prostate up to 40% 5-ARIs reduce further growth rate
Typical Second-Line Therapy: 5- Alpha Reductase Inhibitors Finasteride (Proscar) Inhibits only 5-alpha reductase isoenzyme Type 2 Reduces serum DHT by 70-90% Clinical efficacy after 6 months of therapy Dutasteride (Avodart) Inhibits both Types 1 and 2 5-AR isoenzymes Serum DHT approaches zero Clinical efficacy after 4 months of therapy
Typical Second-Line Therapy: 5- Alpha Reductase Inhibitors Potential side effects Decreased libido Erectile dysfunction Decreased ejaculate volume Gynecomastia Depression, Anxiety Reduce serum PSA levels by 50% after 6 months of therapy
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. He selected 5-ARI therapy You kept him on tamsulosin till 5-ARI took effect at 4 months (dutasteride)
Vignette 55 year-old man, otherwise healthy, bothersome urinary hesitancy, weak stream, nocturia. At 4 months he was doing very well At 5 months, off of tamsulosin, on solitary 5-ARI, he was 70% better than baseline, happier but not thrilled You recommended dual therapy He loves you
Vignette Same man, now 58 years old, doing well except worsening erectile dysfunction You and he share disdain for polypharmacy You stop tamsulosin, keep 5-ARI, start daily tidalafil (5mg PO daily). Efficacy as early as 4 weeks, but reliable at 6 weeks At 6 weeks, you stop 5-ARI, keep solitary tidalafil He and his partner are appreciative
PDE-5 Inhibitors for LUTS Only tidalafil has FDA approval for LUTS Smooth muscle relaxation in prostate and detrusor (bladder) Randomized, placebo controlled trial: Decreased AUASI by 2.8 pts at 6 weeks Decreased AUASI by 3.8 at 12 weeks Side Effects: HA, flushing, back pain, congestion, indigestion Do not use concomitant alpha blocker or nitrates
Vignette Same man, now 60 years old, doing well except lumbar back pain with sciatica He has minimal voiding symptoms: Feels empties well When bladder full, has strong, wide-caliber stream He does have bothersome storage symptoms: Urgency Frequency
Vignette Same man, now 60 years old, doing well except lumbar back pain with sciatica You verify he has a low post void residual urine (50cc) You offer him empiric therapy for storage symptoms v. referral to urology
Vignette Same man, now 60 years old, doing well except lumbar back pain with sciatica He selects empiric therapy You discuss anti-muscarinics v. beta-agonist
Anti-muscarinics for Storage Symptoms Anti-muscarinic agents inhibit detrusor contraction Contraindicated in narrow-angle glaucoma Non-selective (M2 and M3 receptors) Oxybutynin, tolterodine GI, CNS, CV, salivary side effects Selective (M3 specific) E.g.: trospium (Sanctura), also a quaternary amine and perhaps least CNS side effects Can have all side effects as non-selective, usually less often
Beta-agonist for Storage Symptoms Myrbetriq (mirabegron) the only drug of its class First non-antimuscarinic oral drug for the bladder Precautions: increased SBP has been reported not recommended if SBP >180, DBP > 100 Urinary retention reported in combination with anti-muscarinic
Beta-agonist for Storage Symptoms Drug Interactions: see FDA label for full details Contraindicated concurrent thioridazine Major interactions with tramadol, propafenone Moderate interactions: metoprolol, digoxin, TCAs, aripiprazole, SSRIs, et al.
Vignette Same man, now 60 years old, doing well except lumbar back pain with sciatica He selects mirabegron and does well
Parting thoughts Men, like women, may have overactive bladder and may benefit from treatment with betaagonist or anti-muscarinics Women, like men, have a bladder outlet that can behave in an obstructive manner. Many, many women benefit from treatment with alpha blockers.
Parting thoughts Detrusor injection of botulinum toxin is an alternative to anti-muscarinics and beta agonist therapy in both men and women. Sacral neuromodulation is standard treatment for refractory storage symptoms and no risk of retention. Bladder neck injections of botox, transurethral incisions of the bladder neck are alternatives to alpha-blockers in both men and women.
Parting thoughts Transurethral resection of the prostate is an alternative to PDE-5, alpha blockers, 5-ARIs in men. TURP has greater durability, subjective and objective cure than laser, microwave, and thermal therapies of the prostate Starting to see wave of medical failures in older, more morbid patients. Should ve had a TURP sooner instead of prolonged pharmacotherapy?
Quick reference McVary KT, Roehrborn CG, et al: Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia. J Urol. 2011;185:1793-1803 Sarma AV, Wei JT: Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms. N Engl J Med 2012;367:248-57
Unfortunate Realities of PSA Screening Limited healthcare resources force us to be thoughtful about allocation Evidence of benefit for screening is equivocal Issues around overdiagnosis, overtreatment and harms of treatment are well known. Patients (and physicians) are confused
Screening and Prostate Cancer Mortality: results of the European Randomized Study of Screening for Prostate Cancer 13 years of follow up 299/72,891 deaths in screening cohort 462/89,352 in control Absolute mortality difference: 1.28/1000 men 781 men need to be invited, 27 cases of cancer detected to prevent one death
Screening and Prostate Cancer Mortality: results of the European Randomized Study of Screening for Prostate Cancer 68 screening strategies tested for cost-effectiveness Concluded that screening every other year from 55-59 and biopsy with threshold of PSA 3 in this age group Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up Schröder, Fritz H et al.the Lancet, Volume 384, Issue 9959, 2027-2035 Cost-effectiveness of Prostate Cancer Screening: A Simulation Study Based on ERSPC Data Heijnskijk, et al. JNCI 107(1), 2014
PSA at age 60 predicts CaP incidence and outcomes (Gothenburg, et al; Malmo, et al; Carlson, et al BMU) PSA @ age 60 (n=2918 men) % diagnosed w/ca prostate % with CaP metastasis % with CaP Death 0-0.99 1 1.99 2 2.99 3+ 2.5 9 24 37 0.4 0.6 2.5 8 0.1 0.1 1.1 7 Authors conclude no further screening for men with PSA <1 at age 60
Prostate Cancer Screening No more population wide screening, no health fairs and screening vans Fit strategy to underlying risk of the specific patient New markers: 4K, PHI, PCA3, TMPSS2:ERG, SNPs?
Thank you! Chad Baxter, MD Department of Urology cbaxter@mednet.ucla.edu 32 nd Annual UCLA Intensive Course in Geriatric Medicine & Board Review