B E N I G N P R O S TAT I C H Y P E R P L A S I A U P D AT E

64 

Texto completo

(1)

I N T R O D U C T I O N

This booklet summarizes the American Urological Association’s most recently published guidelines. The docu-ments were developed by multidisciplinary panels convened by the AUA and were based on a thorough, critical literature review, underwent peer review process and were ultimately approved by the AUA Board. Some of the documents have been jointly developed with other associations. AUA guide-lines provide the practitioner with clear principles and strate-gies for quality patient care and do not establish a fixed set of rules that preempt physician judgment. Full text of these reports can be viewed on line at www.auanet.org.

The text may contain information about certain drug uses that are not approved by the Food and Drug Administration (FDA). The physician is encouraged to read prescribing information about indications, con-traindications, precautions and warnings.

Current Guidelines on:

Benign Prostatic Hyperplasia

Priapism

Antibiotic Prophylaxis

Male Infertility

PSA

Microscopic Hematuria

Bladder Cancer

1

(2)

B E N I G N P R O S TAT I C

H Y P E R P L A S I A U P D AT E

Recommendations from the Guidelines Panel

Benign prostatic hyperplasia (BPH) can be associated with bothersome lower urinary tract symptoms (LUTS) that affect quality of life by interfering with normal daily activities and sleep patterns. Since the impact of LUTS on a patient’s qual-ity of life is highly variable and is not directly related to any measurable physiologic factors, the patient’s perception of the severity of the condition, and the degree to which it interferes with his lifestyle and causes embarrassment, should be primary considerations in management.

A framework for diagnosis and treatment of BPH in an index patient of greater than 50 years of age without sig-nificant risk of non-BPH causes is presented (Figure 1). Management of other important causes of voiding dys-function is not addressed.

Evaluation of Benign Prostatic Hyperplasia The goal of evaluating patients presenting with LUTS is to establish that the symptoms are due to BPH.

Initial Evaluation

The initial evaluation should include:

a medical history to identify other causes of voiding

(3)

function or comorbidities that may complicate treatment

a physical examination, including both digital rectal and

focused neurological examinations

a urinalysis performed by dipstick testing or microscopic

examination of the sediment to screen for hematuria,

glucose and urinary tract infection (UTI)

measurement of the serum prostate-specific antigen

(PSA) offered to patients 1) with at least a 10-year life expectancy and for whom knowledge of the presence of

prostate cancer would change management, or 2) for whom the PSA measurement may change the manage-ment of the patient’s voiding symptoms

Urine cytology is an optional test in men with a pre-dominance of irritative symptoms, especially with a his-tory of smoking or other risk factors, to aid in the diag-nosis of bladder carcinoma in situ and bladder cancer.

The routine measurement of serum creatinine levels is not recommended.

Symptom Assessment

Symptom quantification is important to determine dis-ease severity, document therapeutic response to therapy and detect symptom progression in men managed by watchful waiting.

Administer the AUA Symptom Index (identical to

3

(4)

the seven symptom questions of the International Prostate Symptom Score [IPSS]).

Administer other validated assessment instruments if

warranted.

Other Diagnostic Tests

Urinary flow rate recording and measurement of

postvoid residual urine usually are not necessary prior to the institution of watchful waiting or medical therapy. However, they may be helpful in patients with a complex medical history and in those desiring invasive therapy.

Initial Management and Preliminary Discussion of Treatment Options with the Patient

Patients with Mild Symptoms

Watchful waiting is the treatment of choice in

patients with mild symptoms of BPH (AUA Symptom Score ≤7) and patients with moderate or severe symptoms who are not bothered by their symptoms (i.e., do not interfere with the daily activi-ties of living).

Patients with Moderate to Severe Symptoms

Treatment options for patients with bothersome

moderate to severe symptoms of BPH (AUA

(5)

Symptom Score ≥8) include watchful waiting and the medical, minimally invasive or surgical therapies defined in Table 1.

Explain the benefits and harms of the BPH

treat-ment options (including watchful waiting) using the information provided in the full text document (on

www.auanet.org), to patients with moderate to severe symptoms (AUA Symptom Score ≥8) who are both-ered enough to consider therapy.

Optional Diagnostic Tests for Patients Who Choose Invasive Therapy

Additional diagnostic tests (pressure-flow

uro-dynamic studies, urethrocystoscopy and ultrasound [transabdominal or transrectal]) are not recom-mended in the initial evaluation of LUTS but are optional in the following settings:

when choosing invasive therapies, particularly if the

out-come of the pressure-flow study may impact choice of intervention

if prostate size and anatomical configuration are

impor-tant considerations for a given treatment modality

Filling cystometography and upper urinary tract

imaging by ultrasonography or excretory urography are not recommended in the typical patient unless the patient has hematuria, UTI, renal insufficiency or a history of urolithiasis or urinary tract surgery.

5

(6)

Treatment Recommendations

Watchful Waiting

Watchful waiting is indicated for patient with mild

or nonbothersome symptoms.

Medical Treatment

Alpha-adrenergic Blocker Therapy

Alfuzosin, doxazosin, tamsulosin and terazosin are

appropriate treatment options for patients with LUTS secondary to BPH and are believed to have equal clinical effectiveness.

Prazosin or phenoxybenzamine should not be used in

this setting.

5 alpha-reductase Inhibitor Therapy

Finasteride and dutasteride are:

appropriate and effective treatments in patients with

LUTS associated with demonstrable prostatic enlargement

indicated for patients with symptomatic prostatic

enlargement but no bother, to prevent disease

progres-sion. [Present the disadvantages of this approach (side effects and the need for long-term daily therapy) to the patient with an estimate of his baseline risk of progres-sion to aid in informed deciprogres-sion making.]

not appropriate for men with LUTS without evidence of

prostatic enlargement

(7)

Combination Therapy

Concomitant use of an alpha-adrenergic receptor

blocker and a 5 alpha-reductase inhibitor is an appro-priate and effective treatment for patients with LUTS associated with demonstrable prostatic enlargement.

Minimally-invasive Therapies

Transurethral Microwave Heat Treatment

Prostatron®, Targis®, CoreThermTMand TherMatrxTM are effective in partially relieving symptoms in men with BPH. Superiority of one specific device over another has not been demonstrated in clinical trials to date.

Because unexpected procedure-related injuries have been

associated with the use of transurethral microwave heat treatment devices, specific safety recommendations have been published by the U.S. Food and Drug

Administration. (FDA 2000 Public Health Notification; for full text, refer to www.fda.gov/cdrh/safety/bph.pdf).

ensure that the patient meets the device’s indications, i.e.,

prostate size indicated for the specific system being used

verify that the patient has not had prior radiation

thera-py to the pelvic area, as these patients are at increased

risk of rectal fistula formation

ensure that the patient understands the risks and

bene-fits, the duration of the procedure, the normal level of pain or discomfort, the importance of reporting any

7

(8)

unusual pain, operation of any emergency stop button,

and the need to remain as still as possible

continually supervise the procedure: verify that the

retention balloons of the urethral catheter and rectal temperature sensor probe are free of leaks, and confirm

the placement of the urethral catheter and rectal temper-ature sensor using acceptable methods

take care not to oversedate the patient; general or spinal

anesthesia should not be used

Transurethral Needle Ablation

Transurethral needle ablation is effective treatment in

partially relieving symptoms of BPH.

Stents

Prostatic stents are associated with significant

com-plications, such as encrustation, infection and chronic pain. Consider their placement only in high-risk patients, especially those with urinary retention.

Surgery

The patient may appropriately select a surgical

inter-vention as his initial treatment if he has bothersome symptoms.

Patients who have developed complications of BPH

are best treated surgically.

(9)

The choices of surgical approach (open or endoscopic)

and energy source (electrocautery versus laser) are technical decisions based on the patient’s prostate size, the individual surgeon’s judgment and the patient’s comorbidities.

Emerging Technologies (Table 2)

Phytotherapeutic agents and other dietary

supple-ments cannot be recommended for treatment of BPH.

Additional studies are required before interstitial

laser coagulation, water-induced chemotherapy and the PlasmakineticTMTissue Management System can be recommended as treatment options: it is not inap-propriate for these options to be offered to the patient, but the uncertainty of outcomes compared to the recommended treatment options should be dis-cussed with the patient.

High-intensity ultrasound and absolute ethanol

injec-tions are investigational at this time and should not be offered outside the framework of clinical trials.

Balloon dilation is not recommended for patients

with symptoms of BPH.

9

(10)

Therapies for Patients With Uncommon or Serious Complications of BPH

Surgery is recommended for patients with the

follow-ing complications:

refractory retention who have failed at least one attempt

at catheter removal. In patients who are not surgical candidates, treatment with intermittent catheterization, an indwelling catheter or stent is recommended.

renal insufficiency clearly due to BPH

recurrent UTIs, recurrent gross hematuria or bladder

stones clearly due to BPH and refractory to other therapies

A bladder diverticulum is not an absolute indication for

surgery, unless it is associated with recurrent UTI or progressive bladder dysfunction.

Concomitant administration of an alpha blocker is an

option prior to attempted catheter removal in patients with urinary retention.

10 Benign Prostatic Hyperplasia

*In patients with clinically significant prostatic bleeding, a course of a 5 alpha-reductase inhibitor may be used. If bleeding persists, tissue ablative surgery is indicated.

Patients with at least a 10 year life expectancy for whom knowledge of the presence of prostate

cancer would change management or patients for whom the PSA measurement may change the management of voiding symptoms.

After exhausting other therapeutic options as discussed in detail in the text. §

Some diagnostic tests are used in predicting response to therapy. Pressure flow studies are most useful in men prior to surgery

(11)

11

F I G U R E 1.

Benign Prostatic Hyperplasia Diagnosis and Treatment

Moderate/Severe Symptoms (AUA/IPSS ≥8)

Discussion of Treatment Options Initial Evaluation • History •Urinalysis*

• DRE & Focused PE •PSA in Selected Patients†

Mild Symptoms (AUA/IPSS ≤7)

or No Bothersome

Symptoms

Watchful Waiting Medical Therapy

Minimally Invasive Therapies Surgery Surgery Patient Chooses Noninvasive Therapy Patient Chooses Invasive Therapy

Optional Diagnostic Tests§ • Pressure Flow • Urethrocystoscopy • Prostate Ultrasound AUA/PSS Symptom Index Assessment of Patient Bother

Presence of • Refractory Retention or Any of the following clearly related to BPH • Persistent Gross

Hematuria‡ • Bladder Stones‡ • Recurrent UTIs‡ • Renal Insufficiency Optional Diagnostic Tests

(12)

12

TA B L E 1.

Treatment Options for Patients with Moderate to Severe Symptoms of Benign Prostatic Hyperplasia

Watchful Waiting

Medical Therapies Alpha-adrenergic blockers Alfuzosin

Doxazosin Tamsulosin Terazosin

5 alpha-reductase inhibitors Dutasteride*

Finasteride

Combination therapy (alpha blocker and 5 alpha-reductase inhibitor)*

Minimally-invasive Transurethral microwave heat treatments

Therapies CoreTherm™*

Prostatron®(various versions) Targis®

TherMatrx™* Transurethral needle ablation UroLume®stent‡

Surgical Therapies Transurethral resection of the prostate Transurethral electrovaporization Transurethral incision of the prostate

Transurethral holmium laser resection/enucleation Transurethral laser vaporization

Transurethral laser coagulation (e.g., visual laser ablation) Open prostatectomy

* Recommendations based on randomized, controlled trials not included in the original analysis of the literature † The Panel assumes that the combination of any effective alpha blocker and 5 alpha-reductase inhibitor probably

(13)

13

TA B L E 2 .

Emerging Therapies*

Phytotherapeutic Agents Absolute Ethanol Injection High-intensity Focused Ultrasound Transurethral Heat-based Therapies

Interstitial laser coagulation Water-induced thermal therapy

Plasmakinetic™ Tissue Management System

(14)

P R I A P I S M

Recommendations from the AUA Erectile Dysfunction Guidelines Update Panel

Priapism, a relatively uncommon disorder, is a medical emergency. Although not all forms of priapism require immediate intervention, ischemic priapism is associated with progressive fibrosis of the cavernosal tissues and with erectile dysfunction. Therefore, all patients with priapism should be evaluated emergently in order to intervene as early as possible in those patients with ischemic priapism. The goal of the management of all patients with priapism is to achieve detumescence and preserve erectile function. Unfortunately, some of the treatments aimed at correcting priapism have the poten-tial complication of erectile dysfunction. Current treat-ment modalities represent a range of options that are applied in a step-wise pattern, with increasing invasive-ness and risk balanced against the likelihood of pro-longed ischemia and permanent damage to the corpora cavernosa if treatment is absent or delayed.

Evaluation of Priapism

Perform historical, physical, and laboratory/radiologic evaluations to differentiate ischemic from nonischemic priapism (Table 1).

(15)

Components of the historical evaluation:

duration of erectiondegree of pain

previous history of priapism and its treatmentuse of drugs that may have precipitated the

episode

history of pelvic, genital or perineal traumahistory of sickle cell disease or other hematologic

abnormality

Components of the physical examination:

focused examination of the genitalia, perineum and

abdomen

• abdominal, pelvic and perineal examination may reveal evidence of trauma or malignancy

Components of laboratory/radiologic evaluation:

CBC

reticulocyte count

hemoglobin electrophoresispsychoactive medication screeningurine toxicology

blood gas testing (Table 2)color duplex ultrasonographypenile arteriography

15

(16)

Management of Priapism

An algorithm for the management of ischemic and non-ishemic priapism is presented in Figure 1.

Ischemic Priapism

Ischemic priapism is a nonsexual, persistent erection characterized by little or no cavernous blood flow and abnormal cavernous blood gases.

In patients with underlying disorders (e.g., sickle cell

disease, hematologic malignancy), intracavernous treatment of ischemic priapism should be undertaken concurrently with systemic treatment of the underly-ing disorder.

Therapeutic aspiration (with or without irrigation), or

intracavernous injection of sympathomimetics (e.g., phenylephrine) may be used as initial intervention.

If priapism persists following aspiration/irrigation,

perform intracavernous injection of sympathomimet-ic drugs and repeat if needed prior to initiating sur-gical intervention.

Phenylephrine is recommended as the

sympath-omimetic agent of choice for intracavernous injection to minimize cardiovascular side effects.

In adult patients, dilute with normal saline to a

concen-tration of 100 to 500 µg/mL. Inject every 3 to 5

(17)

utes for approximately 1 hour before determining

treat-ment failure.

Children and patients with severe cardiovascular diseases

require smaller volumes or lower concentrations.

Observe patients for subjective symptoms and objective

findings consistent with known undesirable effects of theses agents.

Blood pressure and electrocardiogram monitoring are

recommended in high-risk patients.

Consider use of surgical shunts after intracavernous

injections of sympathomimetics has failed.

Consider cavernoglanular (corporoglanular) shunt as

first choice. Perform with a large biopsy needle or scalpel inserted percutaneously through the glans.

Oral systemic therapy is not indicated for treatment

of ischemic priapism.

Nonischemic Priapism

Nonischemic priapism is an uncommon form of pri-apism caused by unregulated arterial flow. It may follow perineal trauma that results in laceration of the cav-ernous artery. In many patients, there is no underlying cause. The erections associated with nonischemic pri-apism are typically neither fully rigid nor painful. Nonischemic priapism is not an emergency and will often resolve without treatment.

17

(18)

Corporal aspiration has only a diagnostic role.

Aspiration with or without injection of sympath-omimetic agents is not recommended as treatment.

Initial management should be observation.

Discuss the following with the patient prior to

ment: chances for spontaneous resolution, risks of treat-ment-related erectile dysfunction and lack of significant consequences expected from delaying intervention.

Perform selective arterial embolization at request of

patient; autologous clot and absorbable gels (nonper-manent therapies) are preferable.

Consider surgery as a last resort: perform with

intra-operative color duplex ultrasonography.

Stuttering Priapism

Stuttering (or intermittent) priapism is a recurrent form of ischemic priapism in which unwanted painful erections occur repeatedly with intervening periods of detumescence.

Treat each episode as described for ischemic

pri-apism.

Trials of gonadotropin-releasing hormone agonists or

antiandrogens may be used, but have not been fully tested. Hormonal agents should not be used in patients who have not achieved full sexual matura-tion and adult stature.

(19)

Consider intracavernous self-injection of

phenyle-phrine in patients who either fail or reject systemic treatment of stuttering priapism.

19

(20)

20

TA B L E 1.

Key Findings in the Evaluation of Priapism

Finding Ischemic Priapism Nonischemic Priapism

Corpora cavernosa fully rigid • ••

Penile pain • ••

Abnormal cavernous blood gases • ••

Blood abnormalities and

hematologic malignancy ✦ ••

Recent intracavernous vasoactive

drug injections ✦ ••

Chronic, well-tolerated tumescence

without full rigidity •• •

Perineal trauma •• ✦

• Usually present; ✦Sometimes present; ••Seldom present

TA B L E 2 .

Typical Blood Gas Values

Source Po2(mm Hg) Pco2(mm Hg) pH

Ischemic priapism

(cavernous blood)* <30 >60 <7.25

Normal arterial blood

(room air) >90 <40 7.40

Normal mixed venous blood

(room air) 40 50 7.35

(21)

21

F I G U R E 1.

Management of Priapism

Cavernous Aspiration with Blood Gas or Doppler Ultrasound Simultaneous Treatment of

Any Underlying Disease (e.g. sickle cell disease)

PRIAPISM*

Nonischemic

Observation

Arteriography & Embolization

Surgical Ligation Aspiration With or

Without Irrigation

Distal Shunting

Repeat Distal or Use Proximal

Shunting Ischemic

History & Physical

Phenylephrine

* Erection greater than 4 hours duration. † Proceed upon treatment failure.

(22)

A N T I B I O T I C P R O P H Y L A X I S

F O R U R O L O G I C A L PAT I E N T S

W I T H T O TA L J O I N T

R E P L A C E M E N T S

Advisory Statement from the AUA and the American Academy of Orthopaedic Surgeons Antibiotic prophylaxis for hematogenous prosthetic joint infection is not indicated in most healthy urologi-cal patients who have had orthopedic surgery that involves the placement of pins, plates and/or screws, or in most healthy urological patients with total joint replacements. However, it is advisable to consider pre-medication in the small number of at-risk patients defined below who are undergoing urologic procedures with a higher bacteremic risk.

Patients at potential increased risk of hematogenous

total joint infection include:

all patients within the first 2 years post-joint

replace-ment

immunocompromised/immunosuppressed patients

patients with co-morbidities

• previous prosthetic joint infections

• malnourishment

• hemophilia

(23)

• HIV infection

• diabetes mellitus

• malignancy

Risk Stratification of Bacteremic Urologic Procedures

Higher-risk Procedures

Prophylaxis for higher-risk procedures should be con-sidered only for patients at increased risk of hematoge-nous total joint infection, as described earlier. No other patients should be considered for prophylaxis on the basis of the implant alone, although antibiotics still may still be indicated for prophylaxis of urinary tract or other infections.

Higher-risk procedures include the following:

any stone manipulation (includes shock wave lithotripsy)

any procedure with transmural incision into urinary

tract (does not include simple ligation with excision or percutaneous drainage procedure)

any endoscopic procedures of upper tract (ureter and

kidney)

any procedure that includes bowel segments transrectal

prostate biopsy

any procedure with entry into the urinary tract (except

for transurethral catheterization) in individuals with higher risk of bacterial colonization:

(24)

indwelling catheter or intermittent catheterization

• indwelling ureteral stent

• urinary retention

• history of recent or recurrent urinary tract infections or prostatitis

• urinary diversion

Lower-risk Procedures

Prophylaxis for lower-risk procedures are not indicated on the basis of the implant alone, although antibiotics still may be indicated for prophylaxis of urinary tract or other infections.

Endoscopic procedures into urethra and bladder without

stone manipulation or incision (includes fulguration and mucosal biopsy, if no incision).

Open surgical or laparoscopic procedures without stone

manipulation or incision into the urinary tract.

πCatheterization for drainage or diagnostic

instrumen-tation, including both transurethral and percutaneous access.

Suggested Antibiotic Prophylaxis Regimens

The dosage should produce an effective tissue concentra-tion at the time of instrumentaconcentra-tion or incision. Prior to prescribing therapy, weigh the potential benefits against the known risks of antibiotic toxicity, allergy, and the development, selection and transmission of microbial resistance.

(25)

Recommended agents include:

a single systemic level dose of a quinolone (e.g.,

ciprofloxacin, 500 mg; levofloxacin, 500 mg; ofloxacin, 400 mg) orally one to two hours preoperatively

ampicillin 2 g IV (or vancomycin 1 g IV over 1 to 2

hours, in patients allergic to ampicillin) plus gentamicin 1.5 mg/kg IV 30 to 60 minutes preoperatively

Urine should be sterile prior to any procedure. If

bacteriuria is present, then the risk of bacteremia is dramatically increased and antibiotic treatment is required prior to manipulation of the urinary tract.

If a patient presents with a recommendation from an

orthopaedic surgeon that is inconsistent with these guidelines, determine the special considerations that may have affected the decision.

(26)

M A L E I N F E RT I L I T Y

Best Practice Policy

Male infertility can be due to a variety of conditions. Some are identifiable and reversible (e.g., ductal obstruc-tion, hypogonadotropic hypogonadism) and others are identifiable but not reversible (e.g., bilateral testicular atrophy secondary to viral orchitis).

Evaluation of the Infertile Male

The goals are to identify:

potentially correctable conditions

irreversible conditions that are amenable to assisted

reproductive techniques (ART) using the sperm of the male partner

irreversible conditions that are not amenable to ART,

and for which donor insemination or adoption are

options

life- or health-threatening conditions that may underlie

the infertility and require medical attention

genetic abnormalities that may affect the health of

off-spring if ART is employed

Perform initial screeningevaluation if:

no pregnancy within one year of unprotected intercourse

a known male infertility risk exists (e.g., cryptorchid

testis)

a known female factor exists (e.g., female age > 35 years)

(27)

a man questions his fertility potential

Components of the initial screeningevaluation:

reproductive history

• coital frequency and timing

• duration of infertility

• childhood illnesses and development

• systemic medical and surgical problems

• sexual history and sexually transmitted diseases

• gonadal toxin including heat exposure

two semen analyses (Table 1)

Perform full evaluation of male infertility if:

initial screening evaluation is abnormal

couples have unexplained infertility

infertility persists when a female factor has been treated

Components of the full evaluation:reproductive history (see above)

complete medical and surgical history

focused physical examination (e.g., penis, testes,

epi-didymides, vasa, varicocele, secondary sex characteristics, digital rectal examination)

two semen analyses

other tests as needed (see next page)

(28)

Other procedures and tests for assessing male fertility

Endocrine Evaluation(Table 2)

Perform if:

sperm count < 10 million/mL

impaired sexual function

clinical findings suggesting a specific endocrinopathy

Components of the initial endocrine evaluation:

serum follicle stimulating hormone (FSH) level

serum testosterone level

Post-ejaculatory Urinalysis (UA)

Perform if ejaculate volume is < 1.0 mL unless the patient has congenital bilateral absence of the vasa def-erentia (CBVAD) or true clinical hypogonadism.

The presence of any sperm in the post-ejaculatory UA in a patient with azoospermia suggests retrograde ejaculation.

Transrectal Ultrasonography (TRUS)

Recommended to identify ejaculatory duct obstruc-tion with azoospermia, palpable vasa and ejaculate volume < 1.0 mL.

(29)

Scrotal Ultrasonography

Recommended if findings on physical examination of scrotum are inconclusive.

Specialized Tests

Recommended in select patients to identify a male contributing factor or to choose therapy:

semen leukocyte count

sperm antibody tests

sperm viability tests

sperm-cervical mucus interaction tests

zona-free hamster oocyte test

computer-aided sperm analysis

Genetic Screening

Most common genetic factors related to infertility are:

cystic fibrosis gene mutations associated with congenital

absence of the vas deferens

chromosomal abnormalities resulting in impaired

testic-ular function

Y-chromosome microdeletions associated with

spermato-genic impairment

Inform patients with:

non-obstructive azoospermia and severe oligospermia

(< 5 to 10 million sperm/mL) that they may have

(30)

mosomal abnormalities or Y-chromosome microdeletions

azoospermia due to CBAVD, congenital bilateral

obstruction of the epididymides or unilateral vasal agen-esis of the potential for a cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormality

Offer:

karyotyping and Y-chromosome analysisto patients who have

nonobstructive azoospermia or severe oligospermia prior to performing intracytoplasmic sperm injection (ICSI)

genetic testing for CFTR mutations to female partners prior

to proceeding with treatments that utilize sperm of men

with CBAVD

genetic counseling whenever a genetic abnormality is

suspected

Evaluation of Specific Conditions Associated with Azoospermia

Absence of the vasa deferentia

Consider abdominal ultrasonography to rule out renal

anomalies that occur with either bilateral or unilateral vasal agenesis. About 25 percent of men with unilateral vasal agenesis and 10 percent of men with CBAVD have unilateral renal agenesis.

Consider TRUS (in patient with unilateral vasal

agene-sis) for evaluation of ampullary portion of existing vas deferens to exclude presence of segmental atresia.

(31)

Bilateral testicular atrophy

With high FSH and normal or low testosterone:

offer genetic testing

With low FSH, bilaterally small testes and low

testos-terone:

recommend serum prolactin measurement and pituitary

gland imaging to identify functioning and nonfunction-ing pituitary tumors

Ductal obstruction

With normal ejaculate volume (> 1.0 mL), no testic-ular atrophy, at least one palpable vas deferens and

Normal FSH Levels

Recommend:

diagnostic testicular biopsy to distinguish between

obstructive and nonobstructive causes of azoospermia

vasography should not be performed with diagnostic

tes-ticular biopsy unless reconstructive surgery is undertak-en at the same time

Marked Elevation of FSH (> 2X normal)

Recommend:

diagnostic testicular biopsy only if sperm retrieval/ICSI

is being considered

(32)

With Low Ejaculate Volume (< 1.0 mL) and Palpable Vasa

Consider etiologies of low ejaculate volume:

retrograde ejaculation

absent emission

ejaculatory duct obstruction

hypogonadism

CBAVD

Recommend:

TRUS (with or without seminal vesicle aspiration and

seminal vesiculography) to identify obstruction in the distal male reproductive tract

testicular biopsy to confirm presence of reproductive

tract obstruction

vasography to identify site of reproductive tract

obstruc-tion only if reconstructive surgery is undertaken during the same time

Management of Obstructive Azoospermia

Consider treatment options:

Surgery

• microsurgical reconstruction of the reproductive tract

• transurethral resection of the ejaculatory ducts (TURED)

or

• sperm retrieval techniques and in vitro fertilization (IVF)/ICSI

(33)

Microsurgical reconstruction of the reproductive tract is

preferable to sperm retrieval with IVF/ICSI in men with prior vasectomy if the obstructive interval is < 15 years and no female fertility risk factors are present, or if patients wish to avoid the risks and costs of IVF/ICSI.

Perform TURED when obstruction of the ejaculatory ducts is at the level of the prostate gland.

Sperm retrieval with IVF/ICSI is preferable to surgical

treatment when:

advanced female age is present

female factors requiring IVF are present

chance for success with sperm retrieval/ICSI exceeds the

chance for success with surgical treatment

cost to the patient favors this approach

Management of Varicoceles

Potential benefits of varicocele treatment:

varicocele treatment should be offered to appropriate

infertile couples because:

• varicocele repair has been proven to improve semen

parameters in most men

• varicocele treatment may possibly improve fertility

• the risks of varicocele treatment are small

Varicocele treatment (repair) should be offered:

when all of the following are present:

• varicocele is palpable

• couple has documented infertility

(34)

• female has normal fertility or potentially correctable

infertility

• male has ≥1 abnormal semen parameter or sperm function test results

in adult men with a palpable varicocele and abnormal

semen analyses but not currently attempting to conceive

in adolescents with objective evidence of reduced

ipsilat-eral testicular size

Varicocele monitoring should be offered:

in young men with normal semen analyses; repeat semen

analyses every one to two years

in adolescents with normal ipsilateral testicular size

Treatment options include:

varicocele repair (surgery or percutaneous embolization)

(this is the primary option in a man with suboptimal semen quality and a normal female partner)

IVF with or without ICSI (this is the primary treatment

option when there is an independent need for IVF/ICSI)

Follow-up:

analyze semen at three-month intervals for at least one

year or until pregnancy occurs

consider intrauterine insemination and ART if infertility

persists after anatomically successful varicocele repair

(35)

35

TA B L E 2

Endocrine Evaluation of Infertility

Clinical Condition FSH LH Testosterone Prolactin

Normal spermatogenesis Normal Normal Normal Normal

Hypogonadotropic hypogonadism Low Low Low Normal

Abnormal spermatogenesis* High/

Normal Normal Normal Normal

Complete testicular failure/

hypergonadotropic hypogonadism High High Normal/Low Normal

Prolactin-secreting pituitary tumor Normal/Low Normal/Low Low High

* Many men with abnormal spermatogenesis have a normal serum FSH, but a marked eleva-tion of serum FSH is clearly indicative of an abnormality in spermatogenesis.

TA B L E 1

Semen Analysis: Reference Values

On at least two occasions:

Ejaculate volume 1.5 - 5.0 ml

PH > 7.2

Sperm concentration > 20 million/ml Total sperm number > 40 million/ejaculate

Percent motility > 50%

Forward progression > 2 (scale 0-4) Normal morphology > 50% normal*

> 30% normal** > 14% normal*** And:

Sperm agglutination < 2 (Scale 0-3) Viscosity < 3 (Scale 0-4)

(36)

P R O S TAT E - S P E C I F I C

A N T I G E N ( P S A )

Best Practice Policy

Prostate-specific antigen (PSA) can be used for early detection and diagnosis of prostate cancer. Used in con-junction with physical examination findings and labora-tory test results, PSA measurement can also help to determine optimal treatment strategies and to monitor for recurrence. Because of the biologic variability of prostate cancer and the lack of a completed randomized, controlled trial that proves the benefit of early detection, the use of PSA for early detection remains controversial.

Use of PSA for Early Detection of Prostate Cancer

Goal of early detection:

identify patients with clinically significant prostate

can-cers at an early stage when treatment is most likely to

be effective

Reliability:

the proportion of clinically significant cancer detected

with PSA is unknown

No universally accepted definition of clinically

signifi-cant or insignifisignifi-cant prostate cancer currently exists.

(37)

Tumor grade appears to be the strongest prognostic factor.

Individualize decisions to use PSA for early detection

of prostate cancer

Candidates for PSA determination (Figure 1):

asymptomatic men 50 years of age with an estimated

life expectancy of > 10 years

men at higher risk (e.g., family history of disease,

African American) should consider testing beginning at

age 40 years

Inform patients of:

PSA sensitivity and specificity:

• If the PSA level is ≤4.0 ng/mL, the likelihood of a

positive test result in patients with prostate cancer is 67.5 to 80% (sensitivity).

• If the PSA level is > 4.0 ng/mL, the likelihood of a negative test result in patients without prostate

can-cer is 60 to 70% (specificity).

Known and potential risks and benefits:

• Advanced prostate cancer is associated with bone pain, inanition, anemia, sexual dysfunction, ureteral

obstruction and bony fractures.

• Treatment-associated toxicities of radical prostatectomy are surgical risks, incontinence and erectile dysfunction.

• Radiotherapy is associated with erectile dysfunction,

bowel or bladder symptoms.

(38)

Performing PSA testing:

conduct a careful medical history prior to measurement

employing both PSA and digital rectal examination

(DRE) is more sensitive than either test alone

postpone for at least three to four weeks following

prostate biopsy or cystoscopy

Confirm presence of cancer with biopsy if:

PSA 4.0 ng/mL

significant PSA rise from one test to the next

or

DRE is abnormal

Interpreting PSA levels:

consider factors that can affect PSA levels

• prostatitis, benign prostatic hyperplasia and prostate cancer

• physical activity

• infections

• medications and herbal compounds

• surgical or medical castration

relate PSA level to prostate cancer risk and extent:

• In men > 50 years of age, likelihood of prostate can-cer is 20 to 30% when serum PSA > 4.0 ng/mL

• PSA levels of 4.0 to 10.0 ng/mL increase the odds of clinically significant, intracapsular prostate cancer by

1.5 to three fold and the odds of extracapsular disease by three to five fold

(39)

• PSA > 10.0 ng/mL substantially increases the risk

that prostate cancer is extraprostatic

• the combination of normal DRE and PSA of ≤4.0 ng/mL does not guarantee absence of prostate cancer

Use of PSA for Pre-treatment Staging of Prostate Cancer

Routine radiologic or surgical staging is not necessary in all cases of newly diagnosed prostate cancer. Clinical examination can identify patients for whom such staging studies are appropriate (Figure 2).

Bone scan:

not required for staging asymptomatic men with

clini-cally localized prostate cancer when their PSA is ≤20.0 ng/mL, unless history or clinical examination suggests bony involvement

consider at diagnosis if patient has poorly differentiated

or high-grade, stage ≥T3 prostate cancer (even if the PSA is ≤10.0 ng/mL)

CT or MRI scans:

generally not indicated for the staging of men with

clin-ically localized prostate cancer when PSA is < 25.0 ng/mL

Pelvic lymph node dissection:

may not be necessary for clinically localized prostate

cancer if PSA is <10.0 ng/mL or if PSA is < 20.0 ng/mL

(40)

and Gleason Score is ≤6

PSA predicts response to local therapy:

Pre-treatment PSA levels correlate with the risk of

extracapsular extension, seminal vesicle invasion and

both regional and distant disease

Serum PSA levels of < 10.0 ng/mL usually predict

responders to local therapy

Use of PSA in the Post-treatment Management of Prostate Cancer

Offer periodic PSA determinations to detect

recur-rence (Figure 3)

PSA levels post-radical prostatectomy:

should decrease and remain undetectable

detectable levels indicate disease recurrence in most

patients

median interval PSA recurrence to cancer death is five to

12 years depending upon the Gleason score

PSA levels post-radiation therapy and cryotherapy:

an acceptable PSA measurement is under debate

should reach nadir (median of 17 months following

radi-ation) and not rise on successive occasions

consider either method to define biochemical absence of

disease:

• Assessment of nadir PSA following treatment:

(41)

Patients with very low (e.g., < 0.5 ng/mL) or

undetectable levels are not likely to demonstrate relapse within five years of treatment

• American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical

recurrence three consecutive rises of PSA above nadir indicates recurrence when measured at three to six month intervals

Pattern of PSA rise after local therapy:

distant disease more likely if PSA:

• fails to fall to undetectable levels after surgery or rises despite radiation or cryotherapy

• rises within 12 months of all forms of local treatment

• doubles in less than six months

local disease more likely if:

• patient develops biochemical recurrence late (i.e.,

> 24 months after local treatment)

• PSA doubling times > 12 months

PSA level predictors in men with metastatic prostate

cancer treated with androgen deprivation:

nadir PSA and percent PSA decline at three and six

months predicts progression-free survival

the degree of PSA decline following second-line treatment

of metastatic disease correlates with disease survival

Following initial treatment for localized disease, if

metastases are suspected, consider bone scan.

(42)

the level of PSA that should prompt a bone scan is

uncertain

Treatment for recurrent disease:

post-radical prostatectomy options include:

• salvage radiation therapy

• androgen deprivation

post-radiation therapy options include:

• androgen deprivation

• cryotherapy

• salvage radical prostatectomy

PRR, Inc. publishers of the journal ONCOLOGY, is pleased to give permission to the American Urological Association to summarize the content and cite the article “Commentary From the AUA Prostate Specific Antigen Best Practice Policy by the PSA Best Practice Policy Task Force” in the 2003 and future editions of the AUA’s Reference Guide for Urologists. We understand that full citation to ONCOLOGY (14(2):267-286, February 2000]) will be given.

(43)

43

F I G U R E 1

Candidates for Early Detection Testing

prostate-specific antigen (PSA)

test results

Men age 50 or more with an anticipated lifespan of 10 or more years Men age 40-50 with a family history of prostate cancer or African American ethnicity

one or more test is abnormal

possible causes: prostate cancer, BPH, prostatitis

staging For definitive diagnosis:

prostate biopsy

both test results are normal

return regularly for PSA and DRE testing

biopsy negative digital rectal examination (DRE) What tests should be offered?

(44)

44

44

F I G U R E 2

Pre-treatment Staging of Prostate Cancer

Gleason score 2-4: lower biologic aggressiveness

Gleason score 5-6: intermediate biologic aggressiveness

Gleason score ≥7: biologically aggressive tumor

Additional tests, based on preliminary staging include: Determine Tumor Grade

(based on the Gleason grading system)

Radiologic staging:

CT or MRI (generally unnecessary if the PSA < 25.0 ng/mL)

Surgical staging:

Pelvic lymph node dissection (may be omitted if the PSA is <10.0 ng/mL or if the PSA is <20.0 ng/mL and the Gleason score is ≤6)

Bone scan:

Generally unnecessary with clinically localized prostate cancer when the PSA is < 20.0 ng/mL

Surveillance Treatment of localized prostate cancer

Surgery Radiotherapy

(45)

45

F I G U R E 3

Post-treatment Management of Prostate Cancer

Goal: monitor recurrence and treat as necessary

Post-surgery: Post-radiotherapy:

Treatment Options: Treatment Options:

For disease progression consider: Surveillance: Detectable PSA indicates

disease recurrence

Recurrence if nadir PSA > 0.5 ng/mL, or 3 consecutive rises in serum

PSA above nadir

Consider regular DRE and PSA tests

•Salvage radical prostatectomy

•Androgen deprivation •Cryotherapy •Salvage radiation

therapy

•Androgen deprivation

• Radical prostatectomy

• Radiation therapy

(46)
(47)

A S Y M P T O M AT I C

M I C R O S C O P I C H E M AT U R I A

Best Practice Policy Recommendations

Microscopic hematuria is an incidental finding often dis-covered as part of a routine examination. Causes of microscopic hematuria range from minor, incidental findings that do not require treatment to highly signifi-cant lesions that immediately threaten the patient’s life (Table 1). Appropriate renal or urologic evaluation should be performed in all patients with asymptomatic microscopic hematuria who are at risk for urologic dis-ease or primary renal disdis-ease. An algorithm for the ini-tial evaluation of asymptomatic microscopic hematuria is presented in Figure 1. Figure 2 presents an algorithm for the urologic evaluation of microscopic hematuria.

Detection and Initial Evaluation

Base initial determination on microscopic

examina-tion of urinary sediment from a freshly voided, clean catch, midstream urine specimen.

✦ ≥3 red blood cells per high-power field (RBC/HPF) on

microscopic evaluation of the urinary sediment from two of three properly collected urinalysis specimens

microscopic hematuria

If the patient is high-risk, one sample is enough.

(48)

Identify whether patients are at high risk for primary

renal disease:

presence of significant proteinuria

presence of renal insufficiency

presence of dysmorphic RBCs in the urine

predominance of red cell casts

elevated serum creatinine level

Identify whether patients are at high risk for urologic

disease:

smoking history

occupational exposure to chemicals or dyes

history of gross hematuria

age > 40 years

previous urologic disorder or disease

history of irritative voiding symptoms

history of recurrent urinary tract infection despite

appropriate use of antibiotics

Nephrology Evaluation

Recommended when initial evaluation of the urinary

sediment identifies a patient with parenchymal renal disease.

If systemic causes are not identified in the diagnostic

evaluation, consider a renal biopsy for prognosis and guidance of therapy.

(49)

Urologic Evaluation

Components of initial evaluation:

careful medical history

physical examination

urethral and vaginal examination in women

clean catch specimen, via catheter if evidence of vaginal

contamination or if phimosis is present

Components of laboratory analysis:

examination of the urine and urinary sediment

determination of RBCs/HPF count

determination of presence of dysmorphic RBCs or red

cell casts

test for presence and degree of proteinuria

test for urinary tract infection (UTI)

measure serum creatinine

other tests as needed

Cytology

Recommended:

when risk factors for transitional cell carcinoma are

present (Figure 1)

as an adjunct to cystoscopic evaluation of the bladder, if

there is a question of irritative voiding symptoms (espe-cially in determination of carcinoma in situ)

in a patient without risk factors for transitional cell

car-cinoma (or perform cystoscopy)

(50)

Obtain urothelial cells which routinely exfoliate into

the urine:

from a voided specimen

from a bladder wash specimen in which bladder is

irri-gated at time of cystoscopy or bladder catheterization

Imaging

Indicated for detection of renal cell carcinoma,

tran-sitional cell carcinoma in the pelvicaliceal system or ureter, urolithiasis and renal infection.

See Table 2 for modalities, advantages and

disadvan-tages.

Use plain abdominal radiography and

ultrasonogra-phy (US) in low-risk patients with a contraindication to iodine contrast media.

Use US and retrograde pyelography for other than

low-risk patients with a contraindication to iodine contrast media.

Magnetic resonance imaging (MRI), although highly

effective for detection of small renal masses, is a sec-ond line test due to cost and limited availability.

(51)

Cystoscopy

Recommended to exclude the presence of bladder

cancer in:

all adults > 40 years of age, or

all adults < 40 years of age with risk factors for bladder

cancer (Figure 1)

Can defer initial procedure in patients at low risk for

bladder cancer (< 40 years without risk factors for bladder cancer), however, urine cytology should then be performed.

Flexible cystoscopy causes less pain and

post-proce-dure complications, and appears to be at least equiva-lent in effectiveness to rigid cystoscopy.

Development of gross hematuria and/or irritative

voiding symptoms (in the absence of UTI) should prompt referral for cystoscopy.

Follow-up

Because the appearance of microscopic hematuria can

precede the development of bladder cancer by several years, follow-up is important.

(52)

Consider repeat urinalysis, voided urine cytology and

blood pressure determination at 6, 12, 24 and 36 months for patients with a negative initial evaluation.

Recommended for patients with persistent hematuria

in whom there is a high index of suspicion for signif-icant underlying disease:

At 6, 12, 24 and 36 months, repeat:

a urinalysis

a voided urine cytology

blood pressure determination

Consider cystoscopy, cytology and/or repeat imaging

for all patients if any of the following occur:

development of gross hematuria,

abnormal urinary cytology, or

irritative voiding symptoms in the absence of infection

Consider further evaluation for renal parenchymal

disease or referral to a nephrologist if hematuria per-sists and hypertension, proteinuria or evidence of glomerular bleeding (red cell casts, dysmorphic RBCs) develop.

(53)

53

TA B L E 1

Reported Causes of Asymptomatic Microscopic Hematuria

Bladder cancer

Renal cell carcinoma

Prostate cancer

Ureteral transitional cell carcinoma

Renal transitional cell carcinoma Metastatic carcinoma Urethral cancer Penile cancer Renal lymphoma Abdominal aortic aneurysm Renal calculus Vesicoureteral reflux Bacterial cystitis Bladder calculus Ureteropelvic junction obstruction Renal parenchymal disease Symptomatic BPH Urethral stricture/meatal stenosis Bladder papilloma Mycobacterial cystitis Pyelonephritis Hydronephrosis Ureteral calculus

Renal artery stenosis

Renal parenchymal disease Renal vein thrombosis Radiation cystitis Bladder diverticulum Atrophic kidney Bladder neck contracture Interstitial cystitis Asymptomatic BPH Papillary necrosis Renal arteriovenous fistula Renal contusion Polycystic kidney Prostatitis Cystocele Neurogenic bladder Cystitis cystica/glan-dularis Ureterocele Eosinophilic cystitis Phimosis Urethrotrigonitis Renal cyst Duplicated collecting system Prostatic calculus

Bladder neck polyps

Urethral polyps Bladder varices/telangiectasia Scarred kidney Trabeculated bladder Urethral caruncle Pseudomembranous trigonitis Urethritis Pelvic kidney Calyceal diverticulum Exercise hematuria Life-threatening Significant, Requiring Treatment Significant, Requiring Observation Insignificant

(54)

54

TA B L E 2

Imaging Modalities for Evaluation of the Urinary Tract

Modality Advantages/Disadvantages

Intravenous urographyConsidered by many the best initial study for evaluation of urinary tract

Widely available and most cost-efficient in most centers

Limited sensitivity in detecting small renal masses

Cannot distinguish solid from cystic masses; therefore, further lesion characterization by ultrasonography, computed tomography or magnetic resonance imaging is necessary

Better than ultrasonography for detection of transitional cell carcinoma in kidney or urethra

Ultrasonography Excellent for detection and characterization of renal cysts

Limitations in detection of small solid lesions (< 3 cm)

Computed tomography Preferred modality for detection and characterization of solid renal masses

Detection rate for renal masses comparable to that of magnetic resonance imaging, but more widely available and less expensive

Best modality for evaluation of urinary stones, renal and perirenal infection and associated complications

(55)

55

F I G U R E 1

Initial Evaluation of Asymptomatic Microscopic Hematuria*

If one or more of the following are present: microscopic hematuria accompanied by sig-nificant proteinuria**

• dysmorphic red blood cells or red cell casts

• elevated serum creatinine level (based on normal reference ranges for men and women)

Exclude benign causes, including menstrua-tion, vigorous exercise, sexual activity, viral illness, trauma and infection

Patient with newly diagnosed asymptomatic microscopic hematura

Evaluation for primary renal disease

Urologic evaluation (see Figure 2) If conditions suggestive of primary renal disease are not present (i.e., normal creatinine level, absence of proteinuria, absence of dysmorphic red blood cells or red cells casts), or if any of the following are present:

• smoking history

• occupational exposure to chemicals or dyes (benzenes or aromatic amines) • history of gross hematuria

• age > 40 years

• previous urologic disorder or disease

• history of irritative voiding symptoms • history of recurrent UTI despite

appropriate use of antibiotics

*— The recommended definition of microscopic hematuria is three or more RBC/HPF on micro-scopic evaluation of two of three properly collected specimens.

(56)

56

F I G U R E 2

Urologic Evaluation of Asymptomatic Microscopic Hematuria

Low-risk patient

•age < 40 years •no smoking history

•no history of chemical exposure

•no irritative voiding symptoms

•no history of gross hematuria •no history of urologic disorder

or disease

High-risk patient

Upper tract imaging

Cytology Cystoscopy Negative Positive Glomerular bleeding or proteinura Isoiated hematuria

Renal biopsy Biopsy controversial Negative for 3

years Persistent hema-turia, hypertension, proteinura, glomerular bleeding Gross hematuria abnormal cytcology, irritative voiding symptoms without infection

No further urologic monitoring

Evaluate for primary renal disease Repeat complete evaluation Positive, atypical of suspicious Cystoscopy Positive Treat Negative Negative Consider Urinalysis blood pressure and cytol-ogy at 6, 12, 24, and

36 months Positive

Treat Treat

Complete evaluation (upper tract imaging, cytology, cystoscopy) Patient without conditions suggestive

of primary renal disease

(57)

Based on articles from UROLOGY, Vol 57, 2001, Grossfeld et al, “Evaluation of Asymptomatic Microscopic Hematuria in Adults: The American Urological Association Best Practice Policy - Part I Definition, Detection, Prevalence and Etiology,” and “Part II: Patient Evaluation, Cytology, Voided Markers, Imaging, Cystoscopy, Nephrology Evaluation and Follow Up,” pages 599-610, Copyright (2001), with permission from Elsevier

(58)
(59)

N O N - M U S C L E - I N VA S I V E

B L A D D E R C A N C E R

Recommendations from the Guidelines Panel

The AUA Bladder Cancer Clinical Guidelines Panel reviewed the literature on bladder cancer from 1964-1998 and extracted and meta-analyzed all relevant data to estimate as accurately as possible both desirable and undesirable outcomes of alternative treatment modali-ties. Comparative data for the following treatment methods were evaluated:

transurethral resection of bladder tumor (TURBT)

with-out adjuvant therapy

• TURBT plus thiotepa

TURBT plus doxorubicin

TURBT plus mitomycin C

• TURBT plus bacillus Calmette-Guerin (BCG)

These recommendations apply to patients with non-muscle-invasive, transitional cell carcinoma of the blad-der, including carcinoma in situ (CIS) as well as stages Ta and T1 tumors. The terms “standard,” “guideline” and “option” used herein refer to the three levels of flexibili-ty for practice policies:

(60)

Standard: When health and economic outcomes are sufficiently well known and there is virtual unanimi-ty about intervention.

Guideline:When health and economic outcomes are sufficiently well known, but agreement on interven-tion is not unanimous.

Option:When 1) health and economic outcomes are not sufficiently well known, 2) preferences among the outcomes are unknown, 3) patient’s intervention preferences are divided and/or 4) patients are indiffer-ent about the alternative intervindiffer-entions.

Characteristics of Stages Ta, T1 and Tis:

Depth of tumor penetration is the crucial element for staging. Table 1 shows the tumor, node, metastasis classifications for all stages of primary tumors, including those addressed in this guideline.

Stage Ta tumors: confined to the urothelium, have a papillary configuration resembling “seaweed” pro-truding into the lumen of the bladder; predominant-ly low grade.

Stage T1 tumors: penetrate below the basement membrane and infiltrate the lamina propria, but not the detrusor muscle. Most T1 tumors are papillary, but many of those with deepest penetration into the lamina propria are nodular.

(61)

CIS (stage Tis): high-grade (anaplastic) carcinoma, confined to the urothelium, but with a flat, disor-dered, nonpapillary configuration and a likelihood of being underdiagnosed; can be focal, multifocal or dif-fuse. On cystoscopic examination, usually appears as a slightly raised, reddened patch of velvety mucosa – but often is endoscopically invisible.

Grade Classification

Gradea highly predictive indicator of tumor pro-gression and recurrence. Bladder carcinomas are grouped into three principal grades based mainly on degree of anaplasia:

low (grade 1): well-differentiated

intermediate (grade 2): moderately differentiated

high (grade 3): poorly differentiated

Treatment Recommendations

Decision-making differences that are based on specif-ic patient circumstances are reflected in recommen-dations for three different index patients.

Recommendation for all index patients:

Standard:Physicians should discuss with the patient the treatment options and the benefits and harms, including side effects of intravesical

treat-61

(62)

ment, especially those side effects associated with a particular agent.

Recommendation for index patient no. 1:

A patient who presents with an abnormal growth on the urothelium, but who has not yet been diagnosed with bladder cancer.

Standard: If the patient does not have an established histological diagnosis, a biopsy should be obtained for pathologic analysis.

Recommendations for index patient no. 2:

A patient with established bladder cancer of any grade, stage Ta or T1, with or without CIS, who has not had prior intravesical therapy.

Standard: Complete eradication of all visible tumors should be performed if surgically feasible and if the patient’s medical condition permits.

Option: Surgical eradication can be performed by one of several methods, including electrocautery resection, fulguration or laser ablation.

Option: Adjuvant intravesical chemotherapy or

(63)

63 immunotherapy is an option for treatment after

endoscopic removal of low-grade Ta bladder cancers.

Guideline: Intravesical instillation of either BCG or mitomycin C is recommended for treatment of CIS and for treatment after endoscopic removal of T1 tumors and high-grade Ta tumors.

Option: Cystectomy may be considered for initial therapy in some patients with CIS or T1 tumors.

Recommendations for index patient no. 3:

A patient with CIS or high-grade T1 cancer who has had at least one course of intravesical therapy.

Option: Cystectomy may be considered as an option for patients with CIS or high-grade T1 cancers that have persisted or recurred after an initial intravesical treatment.

Option: Further intravesical therapy may be consid-ered as an option for patients with CIS or high-grade T1 cancers that have persisted or recurred after an initial intravesical treatment.

(64)

TA B L E 1

Staging of Primary Bladder Cancer Tumors (T)

Ta: Noninvasive papillary carcinoma

Tis: CIS (anaplastic “flat tumor” confined to urothelium)

T1: Tumor invades lamina propria

T2: Tumor invades muscularis propria T2a: Invades superficial muscularis propria T2b: Invades deep muscularis propria

T3: Tumor invades perivesical fat T3a: Invades microscopic perivesical fat

T3b: Invades macroscopic perivesical fat (extravesical mass)

T4: Tumor invades prostate, uterus, vagina, pelvic wall or abdominal wall T4a: Invades adjacent organs (uterus, ovaries, prostate stoma) T4b: Invades pelvic wall and/or abdominal wall

Adapted from the American Joint Committee on Cancer Staging Manual (Fleming, 1997)

Figure

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