Benign Prostatic Hyperplasia

- Increased urinary frequency and urgency

- nocturia

- poor urinary stream

- a sense of incomplete bladder emptying

- postvoid dribbling

- incontinence (less common)

**These symptoms are not specific for BPH

- Medications (diuretics, drugs with autonomic effects)

- Neurologic conditions (spinal cord injury, stroke, dementia, MS)

- Bladder obstruction due to conditions other than BPH

- For pts with mild BPH symptoms, watchful waiting with conservative measures may be appropriate, including the following:

- reduce fluid intake and limit caffeine drinks and alcohol
- review aggravating meds (diuretics, drugs with autonomic effects)
- Evaluate for cognitive impairment, especially correctible causes
- optimize mobility

- alpha-antagonists
--> relaxes the prostatic smooth muscle in the bladder outflow tract
--> acts rapidly (usually within 48 hours)
--> considered first line treatment, producing clinical response in 70% of men
--> all drugs in this class have similar efficacy and tend to improve symptoms by 30-40%
--> Side effects include abnormal ejaculation, postural hypotension, dizziness, and headaches

- 5-alpha-reductase inhibitors
--> decreases the production of dihydrotestosterone, thereby arresting prostatic hyperplasia.
--> shrinkage is slow, and symptoms often do not improve until after 6 months of therapy
--> Side effects include erectile dysfunction, ejaculatory dysfunction, reduced libido, gynecomastia, and breast tenderness.
--> Indications: Often suitable for those who have failed to respond or do not tolerate alpha-antagonsists, those with severe symptoms, and those with an obviously enlarged prostate or a PSA level >1.4 (the latter two factors prostate size and PSA level are strong predictors of BPH disease progression). 5-alpha reductase inhibitors reduce serum PSA levels by 1/2, and reference levels need to be adjusted if a patient is suspected of having or is being followed for prostate cancer.

The Medical Therapy of Prostatic Symptoms (MTOPS) multicenter trial looked at the long-term progress (mean 4.5 years) of patients randomized to either placebo, finasteride (a 5α-reductase inhibitor), doxazosin (an α-antagonist), or both. Monotherapy with either drug had a similar ability to prevent progression of disease (34%-39% compared with placebo) but combination therapy was more effective (66% compared with placebo). Events such as urinary retention or a need for surgery were reduced significantly by finasteride and combination therapy but not by doxazosin alone. However, combination therapy produced more side effects.

- Urinary retention (>1 episode)

- Urinary tract infection

- Bladder stones

- Renal failure with hydronephrosis

- Urinary symptoms with history of urologic surgery or trauma (including traumatic catheterizations)

- Severe BPH symptoms that have not responded to medical therapy.

Open prostatectomy may be the procedure of choice for a severely enlarged or obstructive prostate. Long-term results from randomized trials comparing transurethral resection of the prostate and transurethral microwave thermotherapy show similar outcomes, suggesting the latter may be the preferred minimally invasive option.

The AUA guidelines recommend a baseline assessment with the AUA Symptom Index (www.prostate-cancer.org/tools/forms/aua_symptom_form.html). A score of 0 to 7 represents mild symptoms, 8 to 19, moderate symptoms; and 20 to 35, severe symptoms. Because prostate cancer seldom causes lower urinary tract symptoms, AUA guidelines do not advocate PSA testing in all patients but rather, only in those who have more than a 10-year life expectancy and those for whom PSA levels may influence BPH treatment. In fact, BPH itself often causes a mildly elevated PSA level.

Answer E: A urinalysis is the lab test experts most strongly recommend for INITIAL evaluation of voiding symptoms in a man with suspected BPH.

This elderly man has voiding symptoms that are most consistent with benign prostatic hyperplasia (BPH), a diagnosis that is further supported by the findings of a symmetrically enlarged prostate on physical examination. A urinalysis is the laboratory test experts most strongly recommend in order to screen for urinary abnormalities and evidence of a urinary tract infection. A urine culture may also be desirable, particularly if there is pyuria or bacteriuria noted on urinalysis.

Postvoid residual urine volume can be determined with in-and-out catheterization after the patient spontaneously voids, and is most useful if one suspects overflow incontinence due to outlet obstruction (such as from prostatic hyperplasia) or a flaccid neurogenic bladder (due to conditions affecting the lower motor neurons, such as diabetes mellitus). Incontinence, however, is not part of this patient’s symptom complex.

Prostate cancer seldom causes lower urinary tract symptoms. The American Urological Association guidelines recommend a serum prostate-specific antigen (PSA) level be obtained as a prostate cancer screening test for men with BPH who have more than a 10-year life expectancy and for those for whom PSA levels may influence BPH treatment. In an 84-year-old man with oxygen-dependent chronic obstructive pulmonary disease, a routine PSA would not be warranted. Moreover, an evidence-based review of quality indicators for BPH in the elderly recommended a urinalysis as a routine initial test but did not report the same degree of evidence for routine PSA testing.

A prostate ultrasound is most useful in evaluating suspected prostate cancer and therefore would not be initially ordered to evaluate voiding complaints.

Measurement of serum creatinine is no longer routinely recommended for patients with suspected BPH because multiple long-term, placebo-controlled trials have shown that the incidence of renal insufficiency in men with BPH is the same as in the general population.

It is a BENIGN tumor in men (the most common) that is a histologic diagnosis which can be the driver of medical problems in the future.

50% by age of 50; 80% by age 80.

These are rare:

- urethral stricture

- bladder neck contracture

- bladder neck dysfunction

- striated sphincter dyssynergia

- urinary urgency
- urinary frequency
- nocturia
- straining to void
- weak urinary stream
- feelings of incomplete emptying
- the perceived need to repeat voiding
- rarely urinary incontinence

*With any of these symptoms, a patient should be considered for pharmacologic or surgical treatment ONLY if he has significant, troublesome lower urinary tract symptoms associated with benign prostatic obstruction, or if the situation has created a risk for lower or upper urinary tract dysfunction.

- urinary retention
- renal impairment
- UTI
- gross hematuria
- bladder stones
- bladder decompensation
- Overflow urinary incontinence
- Detrusor overactivity - occurs in ~50% with BPO

There are essentially two mechanisms:

1) A "Static" or "slow" mechanism that leads to increased bulk mediated by the imbalance between cell apoptosis and proliferation via DHT. This is the basis of tx with 5-alpha-reductase inhibitors.

2) A "dynamic" component related to alpha-1-adrenergic receptors that can be effected by medications (e.g. antihistamines that contain alpha-agonist components) and is the basis of treatment with alpha-blockers (e.g. alfuzosin, et. al.)

In an older male patient presenting with lower urinary tract symptoms, with or without some degress of nonsuspicious BPE, bladder outlet obstruction due to BPH should be suspected.

The initial evaluation should include:
- a complete H&P (including meds)
- a International Prostate Symptom Score
- Pelvic and DRE
- UA
- ?PSA test

* A bladder diary is helpful in patients who present with nocturia.
-

IPSS is a set of 7 questions regarding incomplete bladder emptying, mcturition frequency, intermittence, urgency episodes, weak urinary stream, straining at urination, and nocturia. An 8th question relatesto QoL related to LUTS.

Mild Symptoms = 0-7
Moderate Symptoms = 8-19
Severe Symptoms = 20-35

*The IPSS does NOT definitively diagnosis BPO, however, it provides a basline value for a parameter that can be rechecked during a course of pharmacologic management, watchful waiting, or following surgery. It provides a way of assessing progress or regression related to treatment.

The serum PSA test is a commonly performed lab test that has relevance for patients with BPH. As inidicated in the AUA guidelines, "serum PSA has been demonstrated to have an excellent correlation with prostate size and predict the natural history of the condition. Men with higher PSA levels are at greater risk to have future prostate growth, develop deterioration of LUTS and urinary flow rate, experience acute urinary retention, and require BPH-related surgery."

- The drawbacks of PSA is related to it's association also with Prostate Cancer.
- In patients with a life expectance of 10 years or less, a PSA test should NOT be ordered.

- A normal urinary flow rate is 25 mL/sec

- A rate that suggests BPO is <13 mL/sec

Symptoms!

Treatment should be goal directed from the patient perspective.

Watchful waiting vs. Pharmacologic Therapy vs. Surgery are 3 options for BPH.

In general, patients at higher risk for future complications are those with PSA 1.5 ng/mL or greater, increasing PSA levels, and prostate size 30 mL or greater.

These patients should be treated

The alpha-blockers provide the most rapid relief by decreasing the smooth muscle tone in the stroma and prostate capsule, thereby, addressing the "dynamic" component of prostatic obstruction.

- They are considered the most effective monotherapy for treatment of BPO

The 5AR inhibitors decrease prostatic bulk, thereby addressing the static component. It's effects take a long time to observe.

The role of 5AR inhibitors is related to the pathogenesis of BPH

DHT, which is converted from testosterone by 5AR, has a 10x greater affinity for androgen receptors compared with testosterone. DHT promotes prostate cell proliferation, suppresses prostate cell apoptosis, and increases prostate angiogenesis.

- The 5AR inhibitors reduce prostatic bulk by preventing the conversion of testosterone to DHT, which should lead to a smaller prostate, less proliferation, and less vasculature.

According to the AUA BPH Guidelines Committee, similar efficacy has been demonstrated for the 4 alpha-blockers, terazosin, doxazosin, tamsulosin, and alfuzosin.

- They all demonstrate rapid but modest improvement in urinary flow, as well as a decrease in LUTS

- Their side effects uroselectivity differ slightly.

- Side effects of these drugs as a class include:
> fatigue
> orthostatic hypotension
> edema
> rhinitis
> dyspnea
> headache
> angina
> arrhythmia
> impaired sexual dysfunction

- All except tamsulosin have shown to have modest effects on sexual function, although tamsulosin has shown to have a higher incidence of ejaculatory dysfunction.

- Tamsulosin and Alfuzosin have demonstrated relative uroselectivity.

Both 5AR agents have shown similar efficacy and side effect profiles according to the AUA BPH guideline committee.

Side effects include impotence, decreased libido, decreased semen quantity during ejaculation, and decreased serum PSA (decreases ~50%). Gynecomastia is a rare side effect.

The PSA should significantly decrease by approximately 1/2 by 6 months of therapy with a 5AR inhibitor.

**If the PSA score is NOT significantly decreased after 6 months of therapy, this is a possible indication of progression or cancer. Refer to urology for biopsy.

Per the Medical Therapy of Prostatic Symptoms recommendations, combination therapy should be considered fro patients wtih prostate size greater than 30-40 mL or PSA levels greater than 1.4 ng/mL to prevent clinical progression of BPH.

It is considered safe to offer antimuscarinic therapy to those patients on an alpha-blocker with or without a 5-AR inhibitor who continue to experience symptoms of overactive bladder. However, patients with significant post-residual volume (>350 mL) should NOT receive this therapy because there is the potential of increased risk of infection, further bladder decompensation, or renal insufficiency. Close monitoring should be done.

The AUA BPH guidelines committee has taken the position that saw palmetto does not have proven efficacy in treating BPO.

Surgical intervention is recommended in patients in whom BPO causes renal insufficiency, urinary retention, recurrent UTI, bladder calculi, hydronephrosis, or high post-residual volume.