Benign Prostatic Hyperplasia The James Buchanan Brady Urological Institute

The James Buchanan Brady Urological Institute
Benign Prostatic Hyperplasia
Overview
Benign prostatic hyperplasia, a noncancerous enlargement of the prostate gland, is the most common
benign tumor found in men.
As is true for prostate cancer, BPH occurs more often in the West compared to Eastern countries, such as
Japan and China, and may be more common among blacks. Not long ago, a study found a possible genetic
link for BPH in men younger than age 65 who have a very enlarged prostate: Their male relatives were
four times more likely than other men to need BPH surgery at some point in their lives, and their brothers
had a six-fold increase in risk.
BPH produces symptoms by obstructing the flow of urine through the urethra. Symptoms related to BPH
are present in about one in four men by age 55, and in half of 75-year-old men. However, treatment is
only necessary if symptoms become bothersome. By age 80, some 20 to 30% of men experience BPH
symptoms severe enough to require treatment. Surgery was the only option until the recent approval of
drugs that can relieve symptoms either by shrinking the prostate or by relaxing the prostate muscle tissue
that constricts the urethra.
SIGNS & SYMPTOMS
The symptoms of BPH can be divided into those caused directly by urethral obstruction and those due to
secondary changes in the bladder.
Typical obstructive symptoms are:
difficulty in starting to urinate despite pushing and straining
a weak stream of urine; several interruptions in the stream
dribbling at the end of urination
Bladder changes cause:
a sudden strong desire to urinate (urgency)
frequent urination
the sensation that the bladder is not empty after urination is completed
frequent awakening at night to urinate (nocturia)
As the bladder becomes more sensitive to retained urine, a man, may become incontinent (unable to
control the bladder causing bed wetting at night, or inability to respond quickly enough to urinary
urgency).
Burning or pain during urination can occur if a bladder infection or stone is present. Blood in the urine
(hematuria) may herald BPH, but most men with BPH do not have hematuria.
SCREENING & DIAGNOSIS
The American Urological Association (AUA) Symptom Index provides an objective assessment of BPH
symptoms that helps to decide on treatment. However, this index cannot be used for diagnosis, since
other diseases can cause symptoms similar to those of BPH. Therefore, a careful medical history, physical
examination, and laboratory tests are required to exclude such conditions as urethral stricture (narrowing
of the urethra) and bladder irritation from causes other than BPH. In fact, some reports indicate that as
many as 30% of men who undergo prostatic surgery following the usual evaluation do not show evidence
of urethral obstruction from BPH.
A medical history will give clues to conditions that can mimic BPH, such as possible stricture, bladder
cancer or stones, or abnormal bladder function (problems with holding or emptying urine) due to a
neurologic disorder (neurogenic bladder). Strictures can result from urethral damage caused by prior
trauma, instrumentation (for example, catheter insertion), or an infection, such as gonorrhea. Bladder
cancer is suspected if there is a history of blood in the urine.
Pain in the penis or bladder area may indicate bladder stones or infection. A neurogenic bladder is
suggested when an individual has diabetes or a neurologic disease such as multiple sclerosis or
Parkinson's disease, or describes a recent deterioration in sexual function. A thorough medical history
should also include questions about previous urinary tract infections or prostatitis (inflammation of the
prostate that may cause pain in to lower back and the area between the scrotum and rectum, chills, fever,
and general malaise), and any worsening of urinary symptoms when taking cold or sinus drugs. The
physician will also ask whether any over-the-counter or prescription medications are being taken, because
certain varieties can make voiding symptoms worse in men with BPH.
The physical examination may begin with the doctor observing urination to completion to detect any
urinary irregularities. The doctor will manually examine the lower abdomen to check for the presence of a
mass, which may indicate an enlarged bladder due to retained urine. In addition, a digital rectal exam
(DRE) which allows the physician to assess the size, shape, and consistency of the prostate, is essential
for proper diagnosis. This important examination involves the insertion of a gloved finger into the rectum,
but is only mildly uncomfortable. The detection of hard or firm areas in the prostate raises the suspicion of
prostate cancer. If the history suggests possible neurologic disease, the physical may also include an
examination for neurological abnormalities that indicate the urinary symptoms result from a neurogenic
bladder.
A urinalysis, which is obtained in all patients with symptoms of BPH, may be the only laboratory test if
symptoms are mild and no other abnormalities are suspected from the medical history and physical
examination. A urine culture is added if a urinary infection is suspected. With more severe chronic
symptoms of BPH, blood creatinine of blood urea nitrogen (BUN) and hemoglobin are measured to rule out
kidney damage and anemia. Measuring prostate specific antigen (PSA) levels in the blood to screen for
prostate cancer is recommended as well as the DRE. PSA testing alone cannot determine whether
symptoms are due to BPH or prostate cancer because both conditions can elevate PSA levels.
TREATMENT
When is BPH treatment necessary?
The course of BPH in any individual is not predictable. Symptoms, as well as objective measurements of
urethral obstruction, can remain stable for many years and may even improve over time as many as onethird of men, according to some studies. In a recent study from the Mayo Clinic, urinary symptoms did not
worsen over a three-and-a-half-year period in 73% of men with mild BPH. A progressive decrease in the
size and force of the urinary stream and the feeling of incomplete emptying of the bladder are the
symptoms most correlated with the eventual need for treatment. Although nocturia (frequent nighttime
urination) is one of the most annoying symptoms of BPH, it does not predict the need for future
intervention.
If worsening urethral obstruction is left untreated possible complications are: a thickened, irritable bladder
with reduced capacity for urine; infected residual urine or bladder stones; and a backup of pressure that
damages the kidneys.
Decisions regarding treatment are based on the severity of symptoms (as assessed by the AUA Symptom
Index), the extent of urinary tract damage, and the man's and overall health. In general no treatment is
indicated in those who have only a few symptoms and are not bothered by them. Intervention -usually
surgical- is required in the following situations:
inadequate bladder emptying resulting in damage to the kidneys
complete inability to urinate after acute urinary retention
incontinence due to overfilling or increased sensitivity of the bladder
bladder stones
infected residual urine
recurrent severe hematuria
symptoms that trouble the patient enough to diminish his quality of life
Treatment decisions are more difficult for men with moderate symptoms. They must weigh the potential
complications of treatment against the extent of their symptoms. Each individual must determine whether
the symptoms bother him enough, or interfere with his life enough, to merit treatment. When selecting a
treatment, both patient and doctor must balance the effectiveness of different forms of therapy against
their side effects and costs.
Treatment options for BPH
Currently, the main treatment options for BPH are:
watchful waiting
medication
surgery (prostatectomy)
If medications prove ineffective in a man who is unable to withstand the rigors of surgery, urethral
obstruction and incontinence may be managed by intermittent catheterization or an indwelling Foley
catheter (which has an inflated balloon at the end to hold it in place in the bladder). The catheter can stay
in place indefinitely (in which case, it is usually changed monthly).
Watchful Waiting
Because the progress and complications of BPH are unpredictable, a strategy of watchful waiting-meaning,
no immediate treatment is attempted-is best for those with minimal symptoms that are not especially
bothersome. Physician visits are needed about once a year to review the progress of symptoms, carry out
an examination, and do a few simple laboratory tests. During watchful waiting, the man should avoid
tranquilizers and over-the-counter cold and sinus remedies that contain decongestants. These drugs can
worsen obstructive symptoms. Avoiding fluids at night may lessen nocturia.
Medication
Drug treatment of BPH is a new development, and data is still being gathered on the benefits and possible
adverse effects of longterm therapy. Currently, two types of drugs-5-alpha-reductase inhibitors and alpha-
adrenergic blockers-are used to treat BPH. Preliminary research suggests that these drugs improve
symptoms in 30 to 60% of men taking them, but it is not yet possible to predict who will respond to
medical therapy, or which drug will be better for an individual patient.
5-alpha-reductase inhibitors
Finasteride (Proscar) blocks the conversion of testosterone to dihydrotestosterone, the major male sex
hormone found within cells of the prostate. In some men, finasteride can relieve BPH symptoms, increase
urinary flow rate, and actually shrink the size of the prostate, though it must be used indefinitely to
prevent recurrence of symptoms. It may take as long as six months, however, to achieve maximum
benefits from finasteride.
In a study of its safety and effectiveness two-thirds of the men taking the drug experienced
at least a 20% decrease in prostate size
(only about half had achieved this level of reduction by the one-year mark)
one-third of patients had improved urinary flow
and two-thirds felt some relief of symptoms
One study published last year suggests that finasteride may be best suited for men with relatively large
prostate glands. An analysis of six studies found that finasteride only improved BPH symptoms in men
with an initial prostate volume of over 40 cc (cubic centimeters); finasteride did not reduce symptoms in
men with smaller glands. Since finasteride shrinks the prostate, men with smaller glands are probably less
likely to respond to the drug because the urinary symptoms result from causes other than physical
obstruction (for example, smooth muscle constriction). A recent study showed that over a 4-year period of
observation, treatment with finasteride reduced the risk of developing urinary retention or requiring
surgical treatment by 50%
Finasteride causes relatively few side effects. Impotence occurs in 3 to 4% of men taking the drug.
Finasteride may also decrease the size of the ejaculate. Another adverse effect is gynecomastia (breast
enlargement). About 80% of those who stopped taking the drug had a partial or full remission of their
breast enlargement. A study from England found gynecomastia in 0.4% of patients taking the drug.
Because it is not clear that the gynecomastia is caused by the drug or increases the risk of breast cancer,
men taking the drug are being carefully monitored until these issues are resolved.
Finasteride can lower PSA levels by about 50%, but is not thought to limit the utility of PSA as a screening
test for prostate cancer. The fall in PSA levels, and any adverse effects on sexual function, disappear when
finasteride is stopped.
To get the benefits of finasteride for BPH without compromising the detection of early prostate cancer,
men should have a PSA test before starting treatment with finasteride; subsequent PSA values can then
be compared to this baseline value. If a man is already on finasteride and no baseline PSA level was
obtained, the results of a current PSA test should be multiplied by two to estimate the true PSA level. A
fall in PSA of less than 50% after a year of finasteride treatment suggests either that the drug is not being
taken or that prostate cancer might be present. Any increase in PSA levels while taking finasteride also
raises the possibility of prostate cancer.
Alpha-adrenergic blockers
These drugs, originally used to treat high blood pressure, reduce the tension of smooth muscles in blood
vessel walls and also relax smooth muscle tissue within the prostate. As a result, daily use of an alphaadrenergic bloeftv drug may increase urinary flow and relieve symptoms of urinary freurgency, and
nocturia. A number of alpha-l-adrenergic drugs-doxazosin (Cardura), prazosin (Minipress), terazosin
(Hytrin),and tamsulosin (selective alpha I-A receptor blocker- FLOMAX) for example-have been used for
this purpose. One recent study found that 10 mg of terazosin daily produced a 30% reduction of BPH
symptoms in about two-thirds of the men taking the drug. Lower daily doses of terazosin (2 and 5 mg) did
not produce as much benefit as the 10 mg dose. Thus, the authors of this report recommended that
physicians gradually increase the dose to 10 mg unless troublesome side effects occur. Possible side
effects of alpha-adrenergic blockers are: orthostatic hypotension (dizziness upon standing, due to a fall in
blood pressure), fatigue, and headaches. In this study, orthostatic hypotension was the most frequent
side effect. The authors noted that this problem can be mitigated by taking the daily dose of the drug in
the evening. In another study of over 2,000 BPH patients, a maximum of 10 mg of terazosin reduced
average AUA Symptom Index scores from 20 to 12.4 over one year, compared to a drop from 20 to 16.3
in patients taking a placebo.
An advantage of alpha blockers, compared to finasteride, is that they work almost immediately; they have
the additional benefit of treating hypertension when it is present in BPH patients. However, whether
terazosin is superior to finasteride may depend more on the size of the prostate. When the two drugs
were compared in a study published in The New England journal of Medicine, terazosin appeared to
produce greater improvement of BPH symptoms and urinary flow rate than finasteride. But this difference
may have been due to the larger number of men in the study with small prostates, who would be more
likely to have BPH symptoms from smooth muscle constriction, rather than from physical obstruction by
excess glandular tissue. Doxazosin was evaluated in three different clinical studies involving 337 men with
BPH. Patients took either a placebo or 4 to 12 mg of doxazosin a day. The active drug- reduced urinary
symptoms by 40% more than the placebo, and increased the urinary peak flow by an average of 2.2 ml/s
(compared to 0.9 ml/s in the placebo patients).
Despite the previously held belief that doxazosin was only effective for mild or moderate BPH, patients
with severe symptoms experienced the greatest improvement. Side effects-including dizziness, fatigue,
hypotension (low blood pressure), headache, and insomnia-led to withdrawal from the study by 10% of
those on the active drug, and 4% of those taking the placebo. In men treated for hypertension, the doses
of other antihypertensive drugs may need to be adjusted to account for the blood-pressure-lowering
effects of an alpha-adrenergic blocker. These drugs may also induce angina in men with coronary heart
disease. A doctor will be able to determine which individuals are good candidates for their use.
Surgery ( Prostatectomy)
Prostatectomy is a very common-operation: About 200,000 of these procedures are carried out annually in
the U.S. A prostatectomy for benign disease (BPH) involves removal of only the inner portion of the
prostate (simple prostatectomy). This operation differs from a radical prostatectomy for cancer, in which
all prostate tissue is removed. Simple prostatectomy offers the best and fastest chance for improving BPH
symptoms, but may not totally alleviate discomfort. For example, surgery may relieve the obstruction, but
symptoms may persist due to bladder abnormalities.
Surgery is also associated with the greatest number of long-term complications, including:
impotence
incontinence
retrograde ejaculation
(ejaculation of semen into the bladder rather than through the penis)
the need for a second operation (in 10% of patients after five years) due to continued prostate growth or
a urethra stricture resulting from surgery
While retrograde ejaculation carries no risk, it may cause infertility and anxiety. The frequency of these
complications depends on the type of surgery.
Surgery is delayed until any urinary tract infection is successfully treated and kidney function is stabilized
(if urinary retention has resulted in kidney damage). Men taking aspirin should stop taking the drug 7 to
10 days prior to surgery, since aspirin interferes with blood's ability to clot. Transfusions are required in
about 6% of patients after TURP and 15% of patients after open prostatectomy.
Since the timing of prostate surgery is elective, men who may need a transfusion-primarily those with a
very large prostate, who are more likely to experience significant blood loss-have the option of donating
their own blood in advance, in case they need it during or after surgery. This option is referred to as an
autologous blood transfusion.
Transurethral prostatectomy (TURP)
This procedure is considered the "gold standard" of BPH treatment-the one against which other
therapeutic measures are compared. It involves removal of the core of the prostate with a resectoscopean instrument passed through the urethra into the bladder . A wire attached to the resectoscope removes
prostate tissue and seals blood vessels with an electric current. A catheter remains in place for one to
three days, and a hospital stay of one to two days is generally required. TURP is associated with little or
no pain, and full recovery can be expected by three weeks after surgery. In carefully selected cases
(patients with medical problems and smaller prostates), TURP may be possible as an outpatient
procedure.
Improvement after surgery is greatest in those with the worst symptoms. Marked improvement occurs in
about 93% of men with severe symptoms and in about 80% of those with moderate symptoms. The
mortality from TURP is very low (0.1%); however, impotence follows TURP in about 5 to 10% of men and
incontinence occurs in 2 to 4%.
Transurethral incision of the prostate (TUIP)
This procedure was first used in the U.S. in the early 1970s. Like TURP, it is done with an instrument that
is passed through the urethra. But instead of removing excess tissue, the surgeon only makes one or two
small cuts in the prostate with an electrical knife or laser. These incisions relieve pressure on the urethra.
TUIP can only be done on men with smaller prostates. It takes less time than TURP, and can be performed
on an outpatient basis under local anesthesia in most cases. A lower incidence of retrograde ejaculation is
one of its advantages.
Open prostatectomy
An open prostatectomy is the operation of choice when the prostate is very large - e.g.>80 grams-(since
transurethral surgery cannot be performed safely in these men). However, it carries a greater risk of lifethreatening complications in men with serious cardiovascular disease, since the surgery is more extensive
than TURP or TUIP.
In the past, open prostatectomies for BPH were carried out either through the perineum (the area
between the scrotum and the rectum)-called perineal prostatectomy--or through a lower abdominal
incision. Perineal prostatectomy has largely been abandoned for the treatment of BPH due to the higher
risk of injury to surrounding organs, though it is still used for prostate cancer. Two types of open
prostatectomy for BPH-suprapubic and retropubic-employ an incision extending from below the umbilicus
(navel) to the pubis. A suprapubic prostatectomy involves opening the bladder and removing the enlarged
prostatic nodules through the bladder. In a retropubic prostatectomy, the bladder is pushed upward and
the prostate tissue is removed without entering the bladder. In both types of operation, one catheter is
placed in the bladder through the urethra, and another through an opening made in the lower abdominal
wall. The catheters remain in place for three to seven days after surgery. The most common immediate
postoperative complications are excessive bleeding and wound infection (usually superficial). More serious
potential complications include heart attack, pneumonia, and pulmonary embolus (blood clot to the lungs).
Breathing exercises, leg movements in bed, and early ambulation are aimed at preventing these
complications. The recovery period and hospital stay are longer than for transurethral prostate surgery.
RETROPUBIC AND SUPRAPUBIC OPEN PROSTATECTOMY
Misop Han, M.D., M.S. Alan W. Partin, M.D., Ph.D. Modified from Han and Partin Chapter 89, Campbell-Walsh Urology 9th Edition, 2006,
Editors: Wein, Kavoussi, Novick, Partin and Peters., Elsevier Inc.
INTRODUCTION: The treatment options for bladder outlet obstruction due to benign
prostatic hyperplasia (BPH) have been expanded dramatically over the past two decades
with the development of medical and minimally invasive therapies. Minimally invasive
procedures include visual laser ablation of the prostate (VLAP), transurethral
electrovaporization of the prostate (TVP), transurethral needle ablation (TUNA),
transurethral microwave thermotherapy (TUMT), interstitial laser coagulation (ILC) and
transurethral incision of the prostate (TUIP). However, these approaches are usually
reserved for men with moderate symptoms and a small to medium-sized prostate gland.
INDICATIONS: For patients with acute urinary retention, persistent or recurrent urinary
tract infections, severe hemorrhage from the prostate, bladder calculi, severe symptoms
unresponsive to medical therapy and/or renal insufficiency as a result of chronic bladder
outlet obstruction, transurethral resection of the prostate (TURP) or open prostatectomy are
indicated. When compared with TURP, open prostatectomy offers the advantages of lower
retreatment rate, more complete removal of the prostatic adenoma under direct vision and
avoids the risk of dilutional hyponatremia (the TURP syndrome) that occurs in
approximately 2% of patients undergoing TURP. The disadvantages of open prostatectomy,
as compared with TURP, include the need for a lower midline incision and a resultant longer
hospitalization and convalescence period. In addition, there may be an increased potential
for perioperative hemorrhage.
SURGERY DISCUSSION: Open prostatectomy can be performed by either the retropubic
or suprapubic approach. In Retropubic prostatectomy, the enucleation of the hyperplastic
prostatic adenoma is achieved through a direct incision of the anterior prostatic capsule.
This approach to open prostatectomy was popularized by Terrence Millin, who reported the
results of the procedure on twenty patients in Lancet in 1945.
The advantages of this procedure over the suprapubic approach are
1. excellent anatomic exposure of the prostate,
2. direct visualization of the prostatic adenoma during enucleation to ensure complete
removal,
3. precise transection of the urethra distally to preserve urinary continence,
4. clear and immediate visualization of the prostatic fossa after enucleation to control
bleeding, and
5. minimal to no surgical trauma to the urinary bladder.
The disadvantage of the retropubic approach, as compared with the suprapubic
prostatectomy, is that direct access to the bladder is not achieved. This may be important
when one considers excising a concomitant bladder diverticulum or removing bladder
calculi. The suprapubic approach also may be the preferred method when the obstructive
prostatic enlargement includes a large intravesical median lobe. Suprapubic prostatectomy,
or transvesical prostatectomy, consists of the enucleation of the hyperplastic prostatic
adenoma through an extraperitoneal incision of the lower anterior bladder wall. This
approach to open prostatectomy was first carried out by Eugene Fuller in New York in 1894;
it was later popularized by Peter Freyer in London, England, who described the procedure in
1900 and later reported the results of his first 1000 patients in 1912.
The major advantage of this suprapubic procedure over the retropubic approach is that it
allows direct visualization of the bladder neck and bladder mucosa.
As a result, this operation is ideally suited for patients with
1. a large median lobe protruding into the bladder,
2. a clinically significant bladder diverticulum or
3. large bladder calculi.
It also may be preferable for obese men, in whom it is difficult to gain direct access to the
prostatic capsule and dorsal vein complex (. The disadvantage, as compared with the
retropubic approach, is that direct visualization of the apical prostatic adenoma is reduced.
As a result, the apical enucleation is less precise, and this factor may affect postoperative
urinary continence. Furthermore, hemostasis may be more difficult because of inadequate
visualization of the entire prostatic fossa after enucleatioin.
SUMMARY: Open prostatectomy, whether performed via a retropubic approach or a
suprapubic approach, is an excellent treatment option for
1. men with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia
causing a markedly enlarged prostate gland,
2. individuals with a concomitant bladder condition, such as a bladder diverticulum or
large bladder calculi and
3. patients who cannot be placed in the dorsal lithotomy position for a transurethral
resection of the prostate gland.
With improved surgical technique, these procedures can be routinely performed in a precise
manner with minimal hemorrhage. Efficacy, in terms of durable improvement in symptom
score and peak urinary flow rate, is superior than other treatment options available for the
obstructing prostate gland, including transurethral resection of the prostate. Meanwhile,
complications are minimal and the length of hospitalization has been markedly reduced. For
most patients, the length of hospital stay is three days or less. Thus, for the properly
selected individual, an open prostatectomy is a highly effective and well-tolerated operation.
Treatments under investigation
A number of other treatment options have been -or are currently being - evaluated for BPH.
Thermal treatments
These procedures may alleviate symptoms by damaging nerves within the prostate, which
may cause smooth muscle relaxation similar to that which occurs with alpha-adrenergic
blocking drugs. In general, this damage is accomplished by raising temperatures within the
gland to above 113' Fahrenheit. Various methods-microwaves, ultrasound, and radio
frequencies-are used to heat the prostate via devices placed in the rectum or urethra.
Several treatment sessions may be necessary, and most men-will need additional treatment
for BPH symptoms within five years after their initial thermal treatment. Transurethral
needle ablation (TUNA) of the prostate uses low-energy radio waves, delivered by tiny
needles at the tip of a catheter, to heat prostatic tissue. A six-month study of 12 men with
BPH (age 56 to 76) found the treatment reduced AUA Symptom Index scores by 61%, and
produced minor side effects (including mild pain or difficulty urinating for 1 to 7 days in all
the men). Retrograde ejaculation occurred in one patient. Another thermal treatment,
transurethral microwave thermotherapy (TUMT), is a minimally invasive alternative to
surgery for patients with bladder outflow obstruction caused by BPH. Performed on an
outpatient basis under local anesthesia, TUMT damages prostatic tissue by microwave
energy (heat) that is emitted from a urethral catheter.
HEREDITARY BPH STUDY
Evidence is accumulating that benign enlargement of the prostate may also be inherited in
an autosomal dominant pattern in some families. We strongly encourage clinicians to
include a family history of benign prostate enlargement in men who are being treated for
bladder outlet obstruction.
Families with three or more living members who have undergone surgery or medical
therapy for benign prostatic enlargement are eligible for this study. If a patient's family fits
these criteria, and would consider participation, please leave your name and phone number,
and the patient's name, phone number and address on our answering machine: 410-9550355, or by leaving this information in a note to our email address: kwiley@jhmi.edu. We
will contact the patient by mail with details about the study and a questionnaire.
If you have any questions about this study, please contact Sally Isaacs
at sisaacs@jhmi.edu
FACULTY
Please follow the links below to find out more about our team of experts.
Trinity J. Bivalacqua, M.D,
Ph.D
Associate Professor of Urology
and Oncology
Misop Han,M.D.
Brian R. Matlaga, M.D., M.P.H.
Associate Professor of
Associate Professor
Urology
Director of Stone Disease
Director of Ambulatory Care
Regional Director of Community
Urology
Jacek L. Mostwin,M.D., D.Phil,
(Oxon.)
Professor of Urology
Christian P. Pavlovich,
M.D.
Associate Professor of
Urology
Director, Urologic
Oncology
Director, Urologic
Oncology Fellowship
John T. Isaacs, Ph.D.
Professor of Oncology, Urology
Ashley E. Ross, MD, PhD
Assistant Professor, Departments of
Urology, Oncology and Pathology