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Symptomatic improvement

Enhancement of bladder emptying and flow dynamics

Preservation of bladder and upper urinary tract function

Resolution of hematuria, if present

Therapies. Surgical treatment remains the gold standard for removing the transition zone tissue of the prostate. However, there is an increasing demand for conservative therapy driven by cost considerations and by pharmacologic and technical advances.

Surgical therapy

Transurethral resection (transurethral prostatectomy; TURP) provides reliable and immediate improvement in both symptoms and voiding dynamics. A wire loop attached

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to an electrocautery unit is used to resect tissue under direct cystoscopic vision. Complications include bleeding, infection, retrograde ejaculation, bladder neck contracture, urethral stricture, and impotence (rarely). Regional anesthesia is commonly utilized. Transurethral incision (TUI) may be appropriate for patients who have small (<20 g) glands. TUI is associated with a lower incidence of bladder neck contracture and retrograde ejaculation.

Open prostatectomy, or enucleation, is usually reserved for patients with glands larger than 60 g or in whom other pathology exists (e.g., vesical calculus or bladder diverticulum requiring repair).

Laser ablation techniques cause delayed sloughing or more immediate evaporation of obstructing tissue. Numerous laser techniques exist; the results are reasonable with the newest vaporization lasers comparable at 3 years to TURP, unlike other laser techniques. Anticoagulated patients currently represent the most appropriate candidates for this technique because bleeding complications are minimal.

Microwave therapy is a technique for men with mild to moderate symptoms with marginal efficacy.

Intraprostatic stents are available to mechanically relieve bladder outlet obstruction but have seen a declining role. Risks of infection, erosion, migration, encrustation, and severe irritative symptoms limit use to rare patients who are too ill to undergo a more definitive procedure.

Medical therapy is used to relieve symptoms in men with mild to moderate disease. Although objective improvement may be minimal, if symptomatic improvement occurs, treatment is successful.

Selective α1 -sympatholytics block α 1 -receptors in the prostatic capsule and bladder neck

area, reducing outlet resistance and improving symptoms. In men with mild to moderate symptoms of prostatism, these agents represent the most commonly used first -line treatment with fairly good symptomatic improvement. Principal side effects include orthostatic hypotension and asthenia.

5 α-Reductase inhibitors block intraprostatic conversion of testosterone to dihydrotestosterone (DHT), reducing prostatic size and improving symptoms with minimal side effects. Objective symptom improvements have been modest, and a trial of 3–6 months may

slightly be required to determine efficacy. These agents reduce the risk of acute urinary retention and the need for TURP.

Combination Therapy (e.g. 5 α-reductase inhibitor plus α-sympatholytics) has been shown in a

RCT to be superior to single -agent therapy for the prevention of disease progression.

IV Carcinoma

A Prostate tumors

Epidemiology. There is an increasing number of new cases; in the United States, blacks have a higher mortality rate compared with whites, even when the rate is adjusted for age and socioeconomic status, likely due to later presentation.

Etiology. There appears to be an increased risk in men with one or more relatives diagnosed before 70 years of age. A hormonal dependence exists but is not clarified.

Pathology. Approximately 95% of prostatic carcinomas are adenocarcinomas. Transitional cell carcinoma of the prostatic urethra, small cell carcinomas, and sarcomas are uncommon lesions.

The anatomic site of origin is most commonly the peripheral zone, which is felt on DRE. The transition zone, or periurethral zone (area removed at transurethral resection for benign disease), is the other common site of cancer.

Premalignant change. Prostatic–intraepithelial neoplasia (PIN), when high grade, is frequently associated with concomitant adenocarcinoma. Whether it is a true precursor is unknown.

Tumor grading

Grading is the histologic assessment of the metastatic potential of a tumor.

The Gleason grading system is most commonly used: Gleason grade ranges from 1 (low) to 5 (high). The Gleason sum total is derived by adding the most common and the

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second most common grades seen in the specimen; that is: 3 + 2. The sum total is subdivided as low (2–4), moderate, (5–6), and high (7–10).

Diagnosis

Present diagnostic modalities include DRE, PSA serum level, and TRUS.

DRE is a traditional method of cancer detection, assessing for induction, or a “module,” in the prostate and is a means to diagnose some cancers missed by other modalities (e.g., PSA, TRUS).

PSA level. PSA is a serine protease that serves to liquefy semen after ejaculation. It has a diagnostic role as well as a role in following response to cancer treatment. When combined with DRE, determination of the PSA level improves the ability to detect cancers. Free PSA: a subset of total TSA also providing assistance in diagnosis. A low level, <15% of total PSA, correlates with a higher risk of cancer.

TRUS is an operator-dependent technique that is marginally helpful at identifying lesions. TRUS is excellent in aiding or directing biopsies of the prostate.

T (Tumor)

N (Nodes)

N0 No regional lymph node metastases

N1 Single node, under 2 cm

N2 Single node 2–5 cm or multiple nodes <5 cm

N3 One or more nodes >5 cm

M (Distant metastases)

M0 No distant metastases

M1 Distant metastases, bone or viscera

Pelvic lymph node dissection. A routine part of radical prostatectomy to remove the obturator/iliac lymph node packet. Reasonable staging procedure (open or laparoscopically) in high-risk men, based on grade, PSA, and clinical stage, if it will alter recommended treatments.

Prostascint scan and nuclear imaging study to attempt to identify a low -volume recurrence

of cancer in men previously treated. Accuracy and clinical role are still unclear.

Treatment by stage (Table 25 -2)

Clinically localized disease (T1-T2, N0, M0)

Based on the natural history of untreated disease, men with a projected survival of longer than 7–10 years should be considered for aggressive treatment with radiation therapy or radical prostatectomy.

Radiation therapy can be delivered via external beam or radioactive seed implantation. Complications frequently include urinary urgency and frequency, hematuria, strictures, impotence, incontinence, and rectal complaints.

Radical prostatectomy via a retropubic or perineal approach is removal of the prostate, the ampullae of the vas deferens, and the seminal vesicles. The urinary bladder is reanastomosed to the membranous urethra. Complications include bleeding, impotence (30%–100%), incontinence (2%–5%), and rectal injury.

Clinical observation. Serial PSA and DRE monitoring with the use of androgen ablation therapy when disease progression occurs is best utilized in men with a lower than 7- to 10 -year projected survival, or possibly in healthy men with T1 lesions.

Locally extraprostatic disease (stage T3). There is no consensus treatment at present. Newer combination modalities include neoadjuvant androgen ablation with surgery or radiation.

Pelvic lymph node metastases. Most patients are treated by androgen ablation therapy without radiation treatment to the prostate. The possibility of removing the prostate in conjunction with androgen ablation therapy does not clearly improve survival, although it is done in some clinical centers.

Distant metastatic disease (bone, retroperitoneal lymph nodes, or other soft tissue metastases)

The standard treatment is androgen ablation therapy to lower serum testosterone. Methods of lowering testosterone include:

Bilateral scrotal orchiectomy

LHRH agonist. Injections downregulate pituitary LH production, thus lowering serum testosterone.

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Estrogens (e.g., diethylstilbestrol) create negative feedback to the pituitary to inhibit LH secretions (no longer available).

Side effects include impotence, breast enlargement and tenderness (estrogens), hot flashes, fatigue, osteoporosis, and weight gain.

Total androgen blockade

Orchiectomy or an LHRH agonist plus antiandrogen supplement

Antiandrogens are competitive inhibitors at the androgen receptor level.

Numerous studies have been done comparing standard androgen ablation with total androgen blockade, with an unclear possible survival advantage to total blockade.

Survival. Median survival with metastatic disease is 2–2.5 years. Men who have a good biochemical response (PSA nadir <4 ng/mL) have a longer survival than do men who have a poor biochemical response (PSA nadir >4 ng/mL).

Hormone refractory disease is the progression of disease after androgen ablation therapy. Survival averages 12–18 months. To date, no therapies are consistently effective, but several chemotherapy agents are approved with modest efficacy (mitoxantrone, paclitaxel [Taxol]).

B Bladder carcinoma

Epidemiology

In the United States, more than 45,000 new cases per year of bladder carcinoma were diagnosed recently, and men were more commonly affected than women.

Generally, carcinoma of the bladder is a disease of the elderly, with a median age of 67–70 years.

Etiology. Likely contributors to development of bladder carcinoma include:

Occupational exposure to aniline dyes, aromatic amines, and β-naphthylamine

Cigarette smoking

Phenacetin (analgesic) abuse

Chronic inflammation from indwelling urethral catheters, suprapubic tubes, or calculi, which can predispose to squamous cell carcinoma

Schistosoma haematobium cystitis , which also is associated with a high risk for squamous cell carcinoma

History of cyclophosphamide treatment

History of pelvic irradiation

Clinical presentation. Painless hematuria is the most common (85%) presenting symptom. Bladder irritability with urinary frequency, urgency, and dysuria is frequently associated with diffuse carcinoma in situ or invasive cancer.

Diagnosis

Urinalysis may show microscopic hematuria.

Intravenous urogram is used to evaluate the kidneys and ureters but may miss many smaller bladder lesions.

Cystourethroscopy. A thorough inspection of the bladder is required to identify the number and location of the lesions (frequently multifocal) as well as their appearance (papillary or nodular). A saline washing (bladder barbotage) can be performed, and the washings can be evaluated to identify

malignant cells.

Molecular diagnostic tests exist, but sensitivity and specificity vary, making them ineffective screening tests (BTA, NMP-22).

Pathology. Types of bladder carcinoma include:

Transitional cell carcinoma , which accounts for more than 90% of tumors in the bladder

Carcinoma in situ (CIS). Poorly differentiated transitional cell carcinoma confined to the urothelium.

Squamous cell carcinoma , which is associated with Schistosoma haematobium infection (mainly in Egypt) and in patients with chronic cystitis due to foreign bodies

Adenocarcinoma is a rare tumor that usually occurs in the dome of the bladder (urachal remnant). Rarely, it is seen in people born with exstrophy of the bladder.

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Staging is determined based on the following:

Endoscopic resection. The tumor is resected in superficial and deep components. Deep resection is performed to define muscle -invasive disease. All visible tumors should be resected. Random bladder and prostatic urethral biopsies may be performed to determine the multifocal extent of disease.

Pathologic evaluation includes grade of lesion, evidence of invasion into the lamina propria or muscle, and presence of CIS in random bladder biopsies.

Bimanual examination under anesthesia is performed after transurethral resection to evaluate extravesical spread and manual mobility of the primary lesion (e.g., pelvic side wall fixation).

The presence of muscle -invasive disease mandates metastatic evaluation and includes:

CT scan of the abdomen and pelvis to evaluate disease spread to the pelvic or para -aortic lymph chain, liver, or adrenal glands.

Chest radiograph and chest CT scan

A chest radiograph is usually adequate; indeterminate results can be evaluated by CT scan.

CT scan may be best used in patients with known intra -abdominal metastases to define possible pulmonary metastases.

Bone scans should be performed routinely to evaluate bone metastases. Serum alkaline phosphatase is a helpful marker for bony metastases but should not be used exclusively.

Staging system (Table 25 -3)

Treatment

Superficial transitional cell tumor (Ta, T1 lesions)

These tumors are treated primarily by complete transurethral resection. Serial endoscopic

and cytologic follow-up evaluation should be done at regular intervals. Approximately 70% of patients develop recurrences.

Intravesical adjuvant therapy may reduce the recurrence rate to 30%–45%.

Thiotepa (an alkylating agent)

Mitomycin C, which inhibits DNA synthesis

Doxorubicin , which inhibits DNA synthesis

TABLE 25-3 Staging Classifications of Urinary Bladder Cancer

T (Primary tumor)

N (Regional lymph nodes below aortic bifurcation)