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75
P R O S T A T E
D I S E A S E
MARK S. LITWIN
GERHARD J. FUCHS
JACOB RAJFER
T
he prostate is a doughnut-shaped, walnut-sized gland
situated on the male pelvic floor just below the bladder
(Fig. 75.1). The urethra passes through the center of the
prostate, as it conducts urine down into the penis for
elimination. In the postpubertal male, the prostate and
nearby seminal vesicles are responsible for generating and
expressing semen, the carrier fluid that bathes and nourishes spermatozoa after ejaculation. After the fertility
years are over, the prostate continues to secrete semen,
but its physiologic usefulness diminishes. As the male
ages, the prostate grows and may become a source of
morbidity or mortality. This chapter discusses the basic elements of diagnosis and treatment for the two most common pathologic conditions of the prostate: prostate cancer
and benign prostatic hyperplasia.
CASE 1
PROSTATIC CARCINOMA
An asymptomatic 66-year-old black male was found on
digital rectal examination to have a 1-cm firm nodule in
the left lobe of his prostate. He had stable mild essential
hypertension. He took one baby aspirin per day as prophylaxis against heart attacks. His father and a maternal
uncle had died of prostate cancer in their early 70s. The
patient claimed normal erections and had full urinary continence. His serum PSA was 9.2 ng/dl and Hct was 43%.
A transrectal ultrasound-guided prostate needle biopsy
was performed after discontinuation of aspirin for 10 days, 24
hours of prophylactic antibiotics, and a cleansing enema. The
biopsy revealed a Gleason 3 + 2 adenocarcinoma confined to
the left lobe. Chest x-ray and nuclear bone scan were normal.
The patient elected to undergo nerve-sparing radical
retropubic prostatectomy with bilateral pelvic lymph node
dissection. He tolerated the operation without incident
and recovered uneventfully. Pathology examination showed
that the entire left lobe of the prostate was replaced by a
Gleason 3 + 2 adenocarcinoma with 2 small foci of tumor
in the right lobe as well. The lymph nodes and seminal
vesicles were free of tumor. Although he suffered from
temporary stress urinary incontinence, within 6 months
he was completely dry and had experienced return of his
erectile function.
CASE 2
BENIGN PROSTATIC HYPERPLASIA
A 73-year-old male was seen for a 1-year history of progressive obstructive voiding symptoms. He complained of
hesitancy in initiating his stream, decreased flow, intermit545
5 4 6
U R O L O G I C
S U R G E R Y
B
A
FIGURE 75.1
Normal prostate. (A) Coronal section. (B) Transverse section.
tency of his stream, a sensation of incomplete emptying,
and nocturia three times per night. Digital rectal examination revealed an enlarged prostate.
The serum PSA was 2.8 ng/dl. Uroflowmetry revealed
a maximum flow rate of 6.6 ml/sec, with an average flow of
4.5 ml/sec and a total voided volume of 230 ml. Postvoid
residual measured by bladder ultrasound was 70 ml. His
AUA symptom score was 24/35.
The patient chose to try an oral 5α-reductase inhibitor;
however, after 7 months he had experienced only minimal
improvement in his symptoms. He therefore elected to
undergo TURP under spinal anesthesia. He tolerated the
procedure well and experienced a dramatic improvement
in urinary symptoms. At a follow-up visit 12 weeks after
surgery, his symptom score was 6/35, and he was pleased
with the results.
P
GENERAL CONSIDERATIONS
rostate cancer is the most common malignancy and
the second most common cause of cancer death in American males. Its incidence increases with advancing age. In
autopsy studies, up to 60% of men over 60 years old have
been shown to have prostate cancer, although it was often
subclinical during life. Prostate cancer is two to three
times more common and more lethal in black men than in
white men. There also appears to be a hereditary component. Although its cause is unknown, its incidence may be
enhanced by a high fat, low fiber diet. Most prostate cancers are asymptomatic (Case 1). Almost all prostate malignancies are adenocarcinomas arising from the glandular
lining of the prostatic ducts. At the time of initial diagno-
sis, 60% are organ-confined and 40% have evidence of regional or distant spread. In the past, most prostate cancers
were identified on routine rectal examinations; however,
the popularity in recent years of prostate-specific antigen
(PSA) as a screening tool has led to an increase in the diagnosis of prostate cancer based on elevated PSA alone.
The value of population-based screening for prostate cancer is highly controversial; however, the American Cancer
Society currently recommends annual digital rectal examinations beginning at age 50 for most men and at age 40 in
blacks, or if there is a paternal or maternal family history
of prostate cancer.
Prostate cancer is often indolent, with many men living for years after the diagnosis. Some prostate cancers
are more aggressive and, if left untreated, will lead to early
death. The challenge in treating this malignancy is to discern which patients need therapy and which do not.
Benign prostatic hyperplasia (BPH) is a nonmalignant
condition in which progressive enlargement of the prostate
can cause bothersome urinary symptoms (Fig. 75.2). Although BPH also affects older men and may occur simultaneously with prostate cancer, there is no known causal relationship between the two. BPH leads to obstructive voiding
symptoms (Case 2) simply by blocking urine flow from the
bladder to the outer urethra. As the prostate grows larger,
the bladder works harder, and the obstructive symptoms
worsen. In some cases the prostatic urethra may become
completely obstructed, causing acute urinary retention.
Prostate enlargement is very common in older men. It may
or may not cause functional impairment, and this impairment may or may not be bothersome to each individual.
Both function and bother must be considered when evaluating patients and recommending therapy.
P R O S T A T E
D I S E A S E
5 4 7
B
A
FIGURE 75.2 Benign prostatic hyperplasia. (A) Coronal section. (B) Transverse section. Note the
greatly hypertrophied central or periurethral component, and the corresponding decrease in urethral
cross-sectional area.
K E Y
P O I N T S
• Prostate cancer is two to three times more common and
more lethal in black men than in white men
• Most prostate cancers are asyptomatic
• Prostate cancer is often indolent, with many men living for
years after the diagnosis
• Both function and bother must be considered when evaluating patients and recommending therapy
P
DIAGNOSIS
rostate cancer can only be definitively diagnosed by
tissue biopsy. Usual indications for prostate biopsy are palpation of a suspicious firm nodule on rectal examination
(Case 1), or elevation of the PSA. Typically, biopsy is performed as an outpatient procedure with transrectal ultrasound guidance. A spring-loaded, Tru-cut needle is passed
through the ultrasound probe into the prostate gland and
several cores of tissue are removed. If there is no obvious
palpable or ultrasonographic lesion, then several random
tissue samples are taken. Prostate biopsy carries a minimal
risk of morbidity and is very well tolerated without anesthesia. Occasionally, patients require small intravenous
doses of a tranquilizer. The primary risks are bleeding and
infection; patients are asked to avoid aspirin-containing
products or anticoagulants for several days before the
biopsy. Many urologists also prescribe prophylactic antibiotics and a cleansing rectal enema (Case 1).
The pathologist measures the volume of cancer present in the biopsy specimen and determines the grade of
the tumor. The Gleason grade ranges from 1 (well differentiated) to 5 (anaplastic). Each tumor is given two scores,
one for its most common and one for its second most common area of cytologic appearance. Hence, the total Gleason score ranges from 2–10 and is usually presented as
both individual scores separated by a plus sign (Case 1).
Before therapy can begin, tumors must be stratified as
organ confined or metastatic. Staging workup begins with
a digital examination to determine whether the tumor extends outside the prostate. It also includes a chest x-ray
and whole body nuclear scintigraphy bone scan, since
bone is the most common site of spread. A PSA level of
4–8 is mildly elevated, above 8 is clearly abnormal, and
above 50 is strongly suggestive of metastasis. Serum acid
phosphatase measurement is also used to identify metastatic cases. Cancers are clinically staged as A (incidental
without palpable abnormality), B (palpable but confined
to the prostate), C (extending locally outside the prostate),
and D (metastatic to lymph nodes, bone, or other organs).
BPH is diagnosed with a combination of subjective
and objective measures. The American Urologic Association (AUA) symptom scale comprises seven questions that
are answered by the patient and each is scored from 0–5.
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U R O L O G I C
S U R G E R Y
They are then summed into a total AUA symptom score
that ranges from 0–35 (Case 2). The higher the score, the
more severe are the symptoms. Patients must also be
asked how bothered they are by their symptoms, since this
may vary tremendously from patient to patient. Objective
measures include uroflowmetry, in which the patient urinates into a computerized funnel that records volume and
flow rate. An average flow of less than 15 ml/sec usually indicates obstruction (Case 2). Measurement of the postvoid
residual urine by ultrasound or catheterization provides
objective evidence of how well the patient empties his
bladder. The prostate size is estimated by digital rectal examination but can be more accurately measured with
transrectal ultrasound. Intravenous pyelography (IVP) is
sometimes used to demonstrate upper tract dilatation or
deviation of the distal ureters caused by prostatic enlargement. Cystourethroscopy can also be helpful by providing
direct visualization of the obstructing prostate lobes and
the strained bladder muscle. Urodynamic testing, a highly
technical set of pressure measurements at different places
in the bladder, prostate, urethra, and rectum, is sometimes required to quantify the degree of obstruction (Case
2). Objective findings must be correlated with subjective
complaints, since the latter drives therapy decisions.
K E Y
P O I N T S
• BPH is diagnosed with a combination of subjective and objective measures
• Objective findings must be correlated with subjective complaints, since the latter drives therapy decisions
S
DIFFERENTIAL DIAGNOSIS
uspicion of prostate cancer is raised when there is a
prostate nodule or a PSA elevation. Hence, differential diagnosis includes other conditions that cause these findings.
Prostatitis can cause significant elevations in the PSA, despite the absence of malignancy. Chronic prostatitis can
also lead to calcifications that are palpated rectally and may
be confused with malignant nodules. BPH can cause PSA
elevations or asymmetric hyperplastic nodules in the
prostate that may feel suspicious to the novice finger. Severe BPH can also cause acute prostatic infarctions that
produce pain and elevation in the PSA or acid phosphatase. Rectal masses are usually not confused with prostate masses. Since prostate cancer usually causes no symptoms, other diagnoses must be suspected when the patient
presents with specific complaints. Nevertheless, malignancy must be considered and addressed when any older
man seeks urologic evaluation. Ultimately, prostate biopsy
is the definitive test in correctly diagnosing prostate cancer.
BPH must be differentiated from other causes of obstructive bladder symptoms. The most common nonprosta-
tic cause is hypotonic bladder, a condition in which the detrusor muscle fails to contract and adequately express all
the urine. Hypotonic bladder can cause symptoms of decreased flow that are similar to those of BPH. Another common cause of urinary symptoms that can be confused with
BPH is prostatitis. Inflammation or infection of the prostate
gland can lead to irritative voiding symptoms that must be
carefully differentiated from their obstructive counterparts
before therapy is undertaken. Other causes of voiding
symptoms include urethral strictures, obstructing bladder
calculi, posterior urethral valves in young boys, and rare benign urethral polyps. Age is an important clue in the differential diagnosis of BPH. The younger the patient, the less
likely he is to have significant prostatic enlargement.
K E Y
P O I N T S
• Prostatitis can cause significant elevations in PSA, despite absence of malignancy
• Prostate cancer usually causes no symptoms
C
TREATMENT
urrently, prostate cancer treatment is highly controversial. Many physicians fervently believe that because of its
usual indolence, prostate cancer requires no direct intervention. Others believe with equal conviction that these tumors
must be treated. Therapy is directed at the gland itself in
organ-confined disease, and systemically in metastatic disease. In clinically localized tumors, the three options are
radical prostatectomy, external beam irradiation, or observation. In younger men or those who have a greater than 10year life expectancy, operation is indicated. In older men or
those who are not good surgical candidates, radiation is most
appropriate. Observational follow-up, although controversial
in the United States, has been used successfully in Europe,
especially in cases in which the tumor grade is not very
threatening or when life expectancy is less than the projected survival due to the cancer. Carefully considered treatment decisions must include attention to quality of life as
well as survival, and must ultimately be made by the patient.
Radical prostatectomy is usually carried out through a
midline suprapubic incision (or occasionally via a perineal
approach). The external iliac lymph nodes are sampled to
exclude regional spread. If these pelvic nodes are free of
tumor, prostatectomy is performed. Otherwise, it is aborted
and the patient is treated systemically for metastatic disease. Since the gland is precariously situated between the
bladder and the urethra, care must be taken to identify and
preserve the anatomic structures that are adjacent to the
prostate. These include the neurovascular bundles (lateral)
that control penile erection, the urethral sphincter (caudal)
that provides the continence mechanism, and the rectum
(posterior). The prostatic urethra and seminal vesicles are
P R O S T A T E
excised with the gland, and a direct sutured anastomosis reconnects the bladder with the urethra (Fig. 75.3). A closed
suction drain protects the anastomosis for several postoperative days, and a urethral catheter is left indwelling for 3
weeks. Most patients experience temporary stress urinary
incontinence for several months following surgery (Case 1).
Some patients may have persistent problems with urine
leakage; others may develop anastamotic strictures that require dilatation. Although ejaculation is not possible after
radical prostatectomy, erection and orgasm may be maintained following a nerve-sparing operation. Depending on
age and level of preoperative sexual function, patients may
experience erectile impotence due to nerve damage during
operation. Rectal injury is uncommon and usually repaired
primarily at the time of surgery.
Pelvic irradiation may be administered by external
beam over the course of several weeks, or with radioactive
seeds that are surgically implanted in the prostate gland.
Either method is effective at delivering a dose adequate to
kill cancer cells. Side effects of radiation are similar to
those of surgery, although they are less frequent. Radiation proctitis, cystitis, or dermatitis may cause annoying
symptoms; however, they are usually temporary.
Observational follow-up includes regular checkups,
measurement of PSA and acid phosphatase levels, and
bone scans to identify local or metastatic extension. Symptoms are treated as they arise.
The mainstay of therapy for metastatic prostate cancer
is testosterone ablation. Huggins won the Nobel Prize in
Medicine for identifying the hormonal dependency of
prostate cancer cells (a finding he published in 1941). Testosterone ablation may be accomplished by bilateral orchiectomy, injectable agents that interrupt the hypothalamic-pituitary-gonadal axis, or oral antiandrogens. These are often
used in combination.
BPH may be treated with operation, medications, or
watchful waiting, depending primarily on the patient’s
wishes. The historic gold standard therapy for BPH is
transurethral resection of the prostate (TURP) (Case 2), an
endoscopic procedure in which the central core of the
gland is chipped away with an electrocautery loop (Fig.
75.4). Care must be taken not to damage the urethral
sphincter, which is located just caudal to the prostate. The
prostatic urethra, removed during TURP, spontaneously
regenerates within 2 weeks. Since the bladder neck is also
resected during TURP, patients generally experience permanent retrograde ejaculation following the procedure.
Erection and orgasm are not affected. When the prostate is
not large enough to warrant TURP, symptomatic improvement may be obtained by endoscopically incising the
prostate (TUIP). If the gland is too large to be adequately
resected transurethrally, a simple open prostatectomy may
be performed. In this operation, the prostatic capsule is
left intact and the adenomatous central portion shelled
out. Results from this approach are usually dramatic.
D I S E A S E
5 4 9
Nonsurgical therapies have recently become the initial
treatment of choice for many men with BPH. Oral αblockers, usually terazosin or prazosin, may be used to
relax the smooth muscle found inside the prostate and
bladder neck. These drugs may cause dizziness in some
men. Alternatively, the 5α-reductase inhibitor, finasteride,
can be used to shrink the size of the prostate gland by
blocking the stimulatory effects of androgens (Case 2). It
usually takes several months to work and must be continued for life. The only significant side effects of finasteride
are decreases in libido, ejaculatory volume, and PSA level.
For some patients, these agents provide adequate symptomatic relief and have the advantage of avoiding the risks of
operation and anesthesia.
Watchful waiting is appropriate in men who are not
terribly bothered by their symptoms, not good surgical
candidates, or unable to take any of the oral medications.
Patients in chronic urinary retention, for whom surgical
and medical therapies are unsuccessful or inappropriate,
may be managed with bladder catheterization (intermittent or indwelling).
K E Y
P O I N T S
• Prostate cancer treatment is highly controversial
• In clinically localized tumors, the three options are radical
prostatectomy, external beam irradiation, or observation
• Mainstay of therapy for metastatic prostate cancer is testosterone ablation
• BPH may be treated with operation, medications, or watchful waiting, depending primarily on the patient’s wishes
P
FOLLOW-UP
rostate cancer patients are seen every several months
following treatment. PSA levels are invaluable in detecting
recurrence or progression of disease. PSA should be undetectable following prostatectomy and very low following
irradiation. Postsurgical and postirradiation patients must
also be evaluated for urinary incontinence and erectile
dysfunction. If the patient desires, he can receive effective
treatment for either complication. If metastatic disease is
detected at any point, the patient is offered hormonal
therapy (surgical or medical), continued observation, or in
certain cases, irradiation to the prostate fossa. Focal irradiation is also used to treat bone pain arising from metastatic lesions.
BPH patients are followed with careful attention to
their symptoms and the degree of bother they experience.
Regardless of whether patients opt for operation, medications, or watchful waiting, the AUA symptom score is a
useful way to quantify the subjective phenomena associated with BPH. Interval uroflowmetry and measurement
A
B
FIGURE 75.3 (A) Prostate cancer is preferably diagnosed at an asymptomatic stage. (B) Open prostatectomy restabilizes genitourinary continuity and function.
P R O S T A T E
D I S E A S E
A
B
FIGURE 75.4 (A) Transurethral resection prostatectomy (TURP) is performed with cystoscopic guidance. (B) Following succesful TURP, the obstruction to flow is eliminated.
5 5 1
5 5 2
U R O L O G I C
S U R G E R Y
of the postvoid bladder residual may also be used (Case
2). Digital rectal examination and PSA screening are also
performed at regular intervals to increase the likelihood of
diagnosing early stage prostate cancer.
K E Y
P O I N T S
• PSA levels are invaluable in detecting recurrence or progression of prostate cancer
• PSA should be undetectable following prostatectomy and
very low following irradiation
SUGGESTED READINGS
Chute C, Panser L, Girman C et al: The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol
150;85, 1993
An easy to read documentation of the epidemiology of prostatic obstructive symptoms in the adult population.
Gittes R: Carcinoma of the prostate. N Engl J Med 324:236, 1991
This thorough review succinctly summarizes the current
state of basic science and clinical knowledge in the field of
prostate cancer.
Roehrborn C: Objective and subjective response criteria to diagnose benign prostatic hyperplasia. Eur Urol, suppl., 24:2,
1993
This article concisely summarizes the diagnostic evaluation
and therapeutic interventions for men with obstructive
voiding symptoms.
QUESTIONS
1. BPH?
A. Is a precursor of prostate cancer.
B. Requires surgical treatment.
C. May be treated with radiotherapy.
D. May be effectively treated with an α-blocker.
2. Prostate cancer?
A. May spread to bone.
B. May spread to iliac lymph nodes.
C. May be asymptomatic.
D. Can be treated with hormonal therapy.
E. All of the above.
(See p. 604 for answers.)