The lower urinary tract (bladder, prostate, and urethra) can be the source of a significant number of disorders, especially in the aging patient. For men, both benign and malignant prostate diseases pose risk for urinary retention, incontinence, and decline in health-related quality of life. This chapter will examine several of the conditions affecting lower urinary tract function commonly seen in the ambulatory setting. The pathophysiology and epidemiology of these conditions will be addressed, as will strategies for diagnosis and therapy.
Lower Urinary Tract Symptoms
Taken together, dysfunction in the prostate and bladder accounts for the development of a well-described constellation of lower urinary tract symptoms (LUTS) (Table 53.1). These include urinary hesitancy, urinary urgency, nocturia, decreased force of the urinary stream, and incomplete bladder emptying. The traditional view of urethral compression from an enlarging prostate is recognized as inadequate to fully explain the pathophysiology of LUTS. The origin of LUTS is multifactorial, with both benign prostatic hyperplasia (BPH, see below) as well as age-related changes in bladder function contributing to the problem. The complex interplay between bladder dysfunction and BPH has emerged as an area for exploration with regard to both diagnosis and therapy for LUTS.
Prostatitis and interstitial cystitis (see Chapter 36) are other sources of lower urinary tract dysfunction, accounting for a significant number of visits to primary care providers. The cause and pathophysiology of these conditions are often unclear but the symptoms they elicit negatively impact on quality of life and lead to substantial use of health care resources by affected patients. Advances in diagnosis and in disease stratification have helped to guide therapy and to provide additional understanding of the natural history and epidemiology of these conditions.
In addition to benign conditions of the prostate, malignant change also represents a significant health risk in the aging male. Carcinoma of the prostate is currently the second most common form of cancer in American men. Although significant strides have been made in the diagnosis and management of prostate cancer since the advent of serum prostate-specific antigen (PSA) testing in the early 1990s, it is not clear that overall survival has improved.
Examination of The Lower Urinary Tract
Examination of the lower urinary tract begins with palpation of the abdomen and suprapubic region. Although normally confined to the deep portion of the pelvis, the bladder rises into the lower abdomen when distended. With volumes greater than 150 mL, palpation of the bladder becomes possible. Assessment should identify any masses, areas of tenderness, or hernia. The presence of inguinal lymphadenopathy should be noted, as this may indicate either an infectious or malignant condition.
The genital exam in the male begins with visual assessment of the skin, looking for rash or other lesions. Uncircumcised men should have the prepuce retracted to see if they have phimosis or lesions on the glans penis and inner aspect of the foreskin. Carcinoma of the penis is rare in industrialized countries and is extremely unusual in males circumcised in infancy. The testis, epididymis, and spermatic cord should be palpated bilaterally.
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Any masses, asymmetry, tenderness or atrophy should be noted. Scrotal masses can be transilluminated if there is a suspicion of hydrocele or spermatocele. Varicocele is commonly associated with thickening of the spermatic cord, and the presence of a transmitted impulse with Valsalva is often an associated finding. Varicoceles should decompress when patients are in the supine position and the testicle is elevated. Persistent distension of a left-sided varicocele should prompt evaluation of the kidneys to rule out renal vein occlusion by a mass or a malignancy.
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TABLE 53.1 Traditional Classification of Lower Urinary Tract Symptoms (LUTS) |
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Neurologic assessment is an important part of the examination of the lower urinary tract. This should include sensory evaluation in the sacral dermatomes (perineal, perianal, scrotal, penile). Presence of the bulbocavernosus reflex can verify the integrity of local sacral reflex arcs. This reflex can be elicited by gentle compression of the glans penis during rectal examination. Normally, a contraction of the anal sphincter and bulbocavernosus muscles can be felt, signaling integrity of the sacral reflex arcs S2–S4. Anal sphincter tone, gait, and peripheral reflexes should also be assessed as part of the examination.
Rectal examination of the prostate is an essential part of lower urinary tract assessment in men. The examination is useful for defining the size, shape, contour, and consistency of the prostate gland, and for determining the presence of BPH or prostate carcinoma. It is useful also for assessment of tenderness, hypersensitivity, and the presence of any other rectal masses. The lateral lobes and peripheral zone of the prostate are palpable to the examining finger. The anterior aspect and median lobe cannot be examined. As prostate cancer arises most commonly in the peripheral zone, the rectal examination has significant utility in identifying abnormal areas. The prostate can be felt 2 to 5 cm from the anal verge; its normal consistency is similar to that of the tense thenar eminence or the tip of the nose. A median sulcus can be appreciated, and the lateral lobes are most commonly symmetric. BPH often causes loss of the median sulcus as well as inability to palpate the base portions due to increase in size of the gland. It is important to note, however, that the degree of enlargement of the prostate due to BPH does not necessarily correlate with the degree of bladder outlet obstruction or with the severity of symptoms. In contrast to changes associated with BPH, prostate cancer is most often manifest as a firm nodule or nodules. These can be asymmetrically located and of varying size. In the setting of advanced disease, loss of the lateral sulcus can be appreciated. A variety of other conditions affecting the prostate (prostatic calculi, granulomas, and inflammation) also can lead to nodular changes. Approximately 30% to 40% of such nodules are found to be malignant on biopsy.
The rectal examination can be performed in a number of ways. Some prefer to place the patient in the lateral decubitus position, while others have the patient stand, bend at the waist, and place both elbows on the examining table. Adequate palpation can be obtained from either position. An explanation of the process and of the importance of the examination can reduce anxiety. Sufficient lubrication should be used to reduce discomfort, and asking the patient to bear down slightly as the finger passes through the anus can help minimize spasm and resistance.
As an adjunct to physical examination, urinalysis and urine culture (if pyuria is present) should be included in men with LUTS. Testing for PSA may also be useful for further assessment of prostate cancer (see below).
Benign Prostatic Hyperplasia
BPH is characterized by uncontrolled, nonmalignant growth of the prostate. This growth is generally confined to the centrally located transition zone of the gland. As such, it accounts for a diffuse increase in size, rather than for the peripheral nodularity described above, which is a finding more suggestive of malignancy. The condition has its onset most commonly between the 5th and 8th decade of life. The prevalence of BPH in American men is approximately 40% in those older than 60 years old. This rate increases to more than 90% in men older than 80. It is difficult to accurately assess the incidence of BPH from a symptomatic standpoint, as a unified definition of what constitutes the condition has not been established. For this reason, BPH and LUTS are viewed together, along a continuum of symptom and disease progression.
The development of BPH and LUTS is multifactorial. Androgens, estrogen, interaction between prostate stroma and epithelium, and heredity have all been implicated. Although androgens do not cause the hyperplasia associated with BPH, testosterone and dehydrotestosterone (DHT) metabolism play important roles. With advancing age, testosterone levels decline. In the face of this change, the level of estrogen in the blood proportionate to the level of androgens increases, and this in turn can stimulate androgen receptor production in the prostate. Whereas levels of prostatic DHT are relatively constant in the aging male, this greater availability of androgen receptor likely accounts for some modulation of prostate growth (1).
Although increase in prostate size is associated with a greater risk of acute urinary retention and the need for surgical intervention, bulk enlargement does not fully explain the development of LUTS. Prostate size does not necessarily correlate with the degree of obstruction or with the severity of symptoms, and complex interactions between prostatic, urethral, and bladder smooth muscle must be taken into account. The model most commonly described is one that includes compressive effects on the urethra from hyperplastic prostate tissue, and increased dynamic tone in the smooth muscle components of the bladder. This latter phenomenon may be sympathetically mediated. In the face of these influences on bladder outflow obstruction,
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changes in bladder function may develop that account for many bothersome BPH-related symptoms (2).
Diagnosis and Evaluation of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms
The constellation of LUTS (Table 53.1) is nonspecific, with BPH being one potential source. Other etiologies of LUTS include neurologic dysfunction (e.g., multiple sclerosis, Parkinson disease, Alzheimer), urinary tract infection (UTI), diabetes mellitus (DM), urethral stricture, urolithiasis, and bladder carcinoma. The aim of evaluation is to establish whether BPH or another process accounts for the symptoms.
A comprehensive medical history is essential in the workup of LUTS. Comorbid conditions should be identified for their potential influence on voiding dysfunction. Medications should be examined, as many can influence voiding function (e.g., diuretics, cold medicines). Physical examination as described earlier is also important. A useful tool for stratifying symptoms and for assessing their severity is the International Prostate Symptom Score (IPSS) (3). This instrument is useful to establish a baseline, to determine the need for treatment, and to assess outcome. Additional studies to consider include urine cytology, serum creatinine, and PSA. Table 53.2 includes a summary of these studies.
Therapeutic Strategies for Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms
There is wide variability in symptomatology among patients with BPH and LUTS. As complications from these conditions are relatively rare, the patient's perception of the impact of urinary symptoms on his quality of life is the primary determinant of which therapy is selected. Treatment options are generally stratified into four main categories. These include watchful waiting, medical therapy, minimally invasive therapy, and surgical therapy. The majority of symptomatic men pursue nonsurgical therapy in the absence of any of the following conditions: refractory urinary retention, urinary tract infection, persistent gross hematuria, azotemia, or bladder stones because of BPH.
Watchful Waiting
In men who are not greatly bothered by their symptoms or who wish to avoid other intervention, a strategy of watchful waiting can be pursued. This option does not imply therapeutic neglect, but rather a systematic reevaluation of symptoms and of their impact, using the IPSS or another instrument, along with exclusion of any indicators of disease progression. This strategy is sound, as it is unclear whether early intervention in minimally symptomatic men affects the natural history of BPH and LUTS.
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TABLE 53.2 Studies to Consider in the Evaluation of LUTS/BPH |
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Medical Therapy
Medical therapy is very important in the treatment of BPH and resulting LUTS. In keeping with a model that implicates both dynamic smooth muscle tone and bulk enlargement of the prostate in the compressive effects of BPH, two targets emerge for medical therapy. These are the α-adrenergic receptor and the androgen influence of DHT. Table 53.3 includes a summary of the agents used in this regard.
Smooth muscle represents roughly 40% of the cellular constituents of BPH tissue. This smooth muscle is influenced by norepinephrine found in high levels in the prostate. The α1-adrenergic receptor is the mediator of smooth muscle tone, accounting for bladder outlet
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obstruction secondary to prostatic hyperplasia (4). The density of α-adrenergic receptors is increased in the prostate stroma and bladder neck. Based on this observation, α1-adrenergic receptor antagonists were found to alter voiding pressure and flow characteristics in men with symptomatic bladder outlet obstruction. As a result of these effects the so-called “α-blockers” remain an essential component of medical therapy for BPH and resulting LUTS.
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TABLE 53.3 Agents Used for Medical Treatment of BPH/LUTS |
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There are only subtle differences among the various α1-adrenergic antagonists. No single agent has demonstrated superior efficacy. As a group, they do not alter serum PSA levels. All are associated with up to a 50% reduction in symptom score. Differences can be seen in the adverse effects of these medications, with varying degrees of postural hypotension, drowsiness, asthenia, nasal congestion, and retrograde ejaculation. Generally, though, these medications are well-tolerated; only 10% of men must discontinue α-blocker therapy because of side effects.
The rationale for androgen manipulation to modulate BPH and related symptoms relates to the influence of DHT on prostatic hyperplasia and to the observed decrease in prostate size with androgen deprivation. DHT is formed from testosterone by the enzyme 5-α reductase. DHT is then available to bind to the androgen receptor to stimulate hyperplasia. By blocking formation of DHT, inhibitors of 5-α reductase decrease prostate size. Nearly 30% of men will have a 30% reduction in prostate size within 6 months. As a consequence, the risk of acute urinary retention and the need for invasive therapy are reduced (5). These benefits appear to be most prominent in men with larger prostates (greater than 40 g). Two agents, finasteride (Proscar) and dutasteride (Avodart) are currently available.
The members of the class of 5-α reductase inhibitors reduce serum PSA by roughly 50%, but leave testosterone levels essentially unchanged. They do not exert any specific antiandrogenic effects and they have few side effects. Patients occasionally report gynecomastia, a reduction in ejaculate volume, and decreases in erectile function or in libido.
The potential benefits of combined therapy with α1-antagonists and 5-α reductase inhibitors have recently been examined. The Medical Therapy of Prostatic Symptoms (MTOPS) trial found that combined therapy with finasteride and doxazosin led to a 66% reduction in symptom score progression, urinary incontinence, UTI, and azotemia (6). Multidrug therapy also reduced the risk of acute urinary retention and the need for invasive therapy. These results were enhanced beyond either agent alone in comparison to placebo.
In addition to prescription medications, a number of supplements have found favor in the treatment of BPH and LUTS. These phytotherapeutic agents are variable in their formulation and are poorly studied. Nevertheless, they continue to engender great enthusiasm as primary therapy or in combination with standard agents (7). Serenoa repens (saw palmetto) is perhaps the most widely known, withPygeum africanum (African plum) and Hypoxis rooperi (South African star grass, Harzol) also gaining appeal. The mechanism of action of these agents is unknown, although histologic evidence suggests induction of cellular atrophy and epithelial contraction. These changes imply
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an effect similar to that of the 5-α reductase inhibitors, although alterations in serum PSA have not been observed.
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TABLE 53.4 Summary of Minimally Invasive BPH Therapies |
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Minimally Invasive Therapies
A number of minimally invasive therapies have emerged in recent years to compete with traditional surgical approaches. Advances in technology and a greater acceptance of the trade-offs between efficacy, side effects, invasiveness, and recovery have increased the appeal of these treatments. Table 53.4 includes a summary of available options.
Transurethral microwave thermotherapy (TUMT) uses thermal energy to heat the prostate and produce coagulative necrosis in the transition and central zones. A catheter is inserted into the urethra to deliver the heat treatment, which lasts 40 to 60 minutes. The latest generation devices have thermal sensors to monitor rectal temperature and also have elements to provide penile and bulbar urethral cooling to avoid thermal injury. This therapy is office-based and can be performed with local anesthetic or moderate sedation. The tolerance for the procedure in the office setting varies with the device employed and temperature threshold. In sham studies, improvement was seen in symptom scores and flow rate after 12 weeks, suggesting a gradual onset of benefit. This improvement was durable in 67% of men after 5 years in one long-term study (8).
Transurethral needle ablation (TUNA) of the prostate is another minimally invasive therapy using thermal energy to induce coagulative necrosis of prostate tissue. A device similar to a cystoscope is introduced into the urethra to deploy two small needles that pierce the prostate lobes. A series of 3-minute treatments are delivered along the length of the prostate at an average of four to six sites. Intraoperative cooling prevents thermal injury to the urethra. Thermal sensors monitor device impedance based on tissue characteristics to prevent collateral injury and enhance safety. The procedure has a greater anesthetic requirement than TUMT because of a higher final temperature. It is usually done in an ambulatory surgery center or hospital setting. Improvement develops in the 4 to 12 weeks following the procedure. A 77% improvement in symptom score was noted 1 year after therapy in a multicenter study (9). The therapy is additionally useful in men with enlargement of the middle lobe of the prostate.
A number of laser devices have been developed to treat BPH. Some of these devices are used for interstitial tissue destruction (similar to TUMT and TUNA) whereas others are designed for more formal tissue ablation and removal. The characteristics of the interstitial devices are similar to microwave and radiofrequency therapies. Lasers with a tissue ablative effect produce results similar to those of transurethral resection of the prostate but have less blood loss.
Expandable wire-mesh stents have been used to relieve bladder outlet obstruction due to BPH. These devices can be placed cystoscopically under moderate sedation and provide immediate relief of prostatic occlusion. Because of side effects of encrustation, stent occlusion, and occasional perineal pain, prostatic stents are generally reserved for men of advanced age with significant comorbid conditions and urinary retention (10).
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The class of minimally invasive prostate therapies for BPH share a low rate of complication in terms of incontinence, erectile dysfunction, stricture formation, retrograde ejaculation, blood loss, or metabolic derangement.
Surgical Therapy
The gold standard for surgical therapy continues to be transurethral resection of the prostate (TURP). The procedure involves removal of prostate tissue using a wire loop and electrocautery. There is typically a 1- to 2-day hospital stay for TURP. General or spinal anesthesia is required. The results of TURP in terms of symptom relief and improvement in urinary flow rate are the benchmark for other therapies. Symptom improvement can be expected in up to 88% of men following TURP. The magnitude of symptom reduction approaches 85% (11). These results appear durable over a 5- to 10-year period. While concern about perioperative complications, such as bleeding or the so-called “TUR syndrome” (an uncommon occurrence marked by confusion, nausea, vomiting, hyponatremia, and fluid overload thought to be due to the absorption of irrigating fluid into the systemic circulation), have increased the popularity of the minimally invasive therapies over TURP, mortality with TURP continues to be low (<1.0%) when controlled for comorbidity and age. Morbidity from TURP is higher than with the minimally invasive therapies. Potential adverse effects include retrograde ejaculation (75%), urinary incontinence (1%), and bladder neck contracture (1%). For men refractory to minimally invasive therapy or with a history of persistent urinary retention, TURP remains the procedure of choice.
In men with extremely large prostates because of BPH (>80 g), open prostatectomy continues to have a role. This procedure requires an abdominal incision and extraction of the adenomatous prostate tissue with preservation of the prostatic capsule. This procedure is also indicated if there are bladder stones, a bladder diverticulum, or another process requiring simultaneous surgical therapy. The procedure requires general anesthesia and a hospital stay of 2 to 4 days. While mortality rates are similar to those after TURP, the long-term adverse effects of open prostatectomy are likely higher. Erectile dysfunction may be seen in 5% to 15% of men having open prostatectomy, and urinary incontinence occurs in 3% to 5%. Symptomatic relief is high with open prostatectomy, and this procedure continues to have a limited but essential role in surgical management of BPH.
Complications of BPH
Untreated BPH can lead to a number of significant complications. These include urinary retention, bladder stones, UTI, incontinence, deterioration of bladder function, decline in renal function, hematuria, and even death. The incidence of acute urinary retention has declined over time, with current estimates of 5% to 7%. Impaired renal function is an uncommon consequence of BPH in the United States. Current cross-sectional studies find the risk of renal failure to be 2% to 3%.
Prostate Cancer
Although the incidence of prostate cancer has declined in recent years, it continues to be the most commonly diagnosed malignancy in American men, and the second most common cause of cancer death. A number of factors influence these figures including age, ethnicity, race, diet, and geography. Prostate cancer is primarily a disease of advancing age. For a man aged 40 to 59 years, the chance of developing prostate cancer is 1 in 53. This incidence increases to 1 in 7 for a man age 60 to 79 years. Racial differences are evident, with the incidence of prostate cancer in African American men the highest (250/100,000 at its peak), and in Asian American men the lowest (82/100,000). A positive family history can increase the risk of prostate cancer significantly, doubling in men having a first-degree relative with prostate cancer, and increasing as much as 5 to 11 times with two or three affected first-degree relatives (12).
Certain dietary effects have been suggested to be important in the development of prostate cancer (13). A high-fat diet has been linked to the development of advanced disease, and a diet poor in the antioxidant lycopene and in the trace element selenium has been observed to increase overall prostate cancer risk. The mechanisms of these associations are not known, nor are there firm recommendations about the limitation or supplementation of these dietary components to minimize the chances of developing prostate cancer.
Prior to the development of advanced disease, prostate cancer is associated with few symptoms. Unlike BPH, prostate cancer rarely causes bladder outlet obstruction, pain, or other changes in lower urinary tract function. As a consequence, the diagnosis of potentially curable disease relies on physical examination and on serum PSA evaluation. As noted earlier, digital rectal exam is helpful for detecting prostate induration or the presence of palpable nodules. These findings should prompt additional evaluation by a urologist. As for the utility of PSA testing, significant controversy exists. Many advocate the use of PSA screening in men beginning at age 50, or at age 40 in African American men or in men with a positive family history. The age at which PSA testing should be discontinued is unclear. In general, curative therapy for prostate cancer has a 7- to 10-year lead time. As such, eligible men should have at least a 10- to 12-year life expectancy. With current survival data for American men, an age cutoff of 75 years is reasonable. Beyond this cutoff, prostate cancer
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screening is unlikely to identify men with localized disease who will benefit from intervention.
Since the widespread use of PSA in the mid-1980s for the detection of prostate cancer, both age and stage migration have been observed. A greater proportion of younger men with localized disease continues to be identified. And while overall prostate cancer mortality has declined over the last decade, it is unclear whether PSA screening accounts for this change (14). Attempts to refine the utility of PSA testing have led to the development of concepts such as PSA density (PSAD) and PSA velocity (PSAV) as well as measurement of free-PSA.
As much of the serum PSA is produced by benign prostate tissue, a threshold level may exist that can stratify malignant change. The quotient of serum PSA and the prostate volume as determined by transrectal ultrasound evaluation defines PSAD. In men with PSA values between 4 and 10 ng/mL, a PSAD >0.15 may increase the likelihood of prostate cancer. The rate of change in serum PSA may also enhance the detection of prostate cancer, as studies demonstrate more rapid rise in PSA in the presence of malignancy. PSAV is the change in PSA divided by time, and levels >0.75 ng/mL/year in men with PSA levels between 4 and 10 ng/mL may be associated with a greater incidence of prostate cancer. Men with prostate cancer have also been shown to have a greater percentage of total PSA complexed to α1antichymotrypsin. As a consequence, a low “free” PSA fraction is more commonly associated with prostate cancer. As such, the ratio of free PSA/total PSA can be used to further weigh other clinical data. In spite of the controversy about the role of PSA testing, an abnormal PSA value should prompt further evaluation by a urologist.
The presence of a suspicious prostate nodule on rectal examination or an abnormal PSA value most commonly prompts needle biopsy to establish a histologic diagnosis. The incidence of prostate cancer detection from ultrasound-guided biopsy is roughly 30% to 35%.
Biopsy of the Prostate
Biopsy of the prostate is indicated if a man has an elevated (PSA) or an abnormal digital rectal examination (DRE). Patients having a prostate biopsy commonly receive antibiotic prophylaxis with a fluoroquinolone for two or three doses. They are instructed to discontinue aspirin and other medications that might alter platelet function before the procedure. Following placement in the lateral decubitus position, an ultrasound probe is gently introduced into the rectum. Transverse and sagittal images of the prostate are obtained to assess contour, volume, and any nodularity. A prostatic block may be administered using image guidance and local anesthetic. In the sagittal plane, core biopsies of the prostate are obtained from the base, body, and apex of the gland. The specific protocol varies among practitioners, with most following a sextant pattern in each of the prostate lobes, for a total of 12 core samples. The procedure lasts 15 to 20 minutes and is well-tolerated. Analgesia is not commonly required following transrectal ultrasound (TRUS)-guided biopsy of the prostate. Postprocedure complications can include rectal bleeding, hematuria, and sepsis.
Staging of Prostate Cancer
The histologic stratification of prostate cancer makes use of the Gleason scoring system. This schema divides the cancer into five categories, or patterns, based on histologic features. Gleason pattern 1 is the most well-differentiated and Gleason pattern 5 the most poorly differentiated. The two most common patterns are assessed throughout the specimen and these are added to give a Gleason score. In this way, the Gleason score can vary between two (1 + 1) and ten (5+5). A score of 10 is indicative of high-grade, poorly differentiated prostate cancer.
Prostate cancer staging can be enhanced by combining histologic information with clinical assessment of tumor extent (T stage) and serum PSA (15). Probability tables have been constructed based on clinical and histological data to give clinicians prognostic information about the likelihood of organ-confined disease, lymph node involvement, and cure.
Table 53.5 describes the staging scheme based on the TNMsystem. StageT1definesnonpalpable, organ-confined prostate cancer. When diagnosed in fragments of tissue submitted at the time of treatment for presumed BPH and obstructive voiding symptoms (by TURP or simple prostatectomy), the T1 stage is subdivided. If discovered in less or more than 5% of the specimen, stages T1a and T1b are defined, respectively. In the setting of nonpalpable disease and an elevated serum PSA, biopsy proven prostate cancer is classified as stage T1c. Controversy exists about the appropriate management of stage T1a disease. In the absence of any other local or distant evidence of prostate cancer, these low-volume occurrences are often of low grade. As such, an observational course is most often recommended, especially in patients older than 65 years of age. For stage T1b or T1c, watchful waiting (see below) is an option, but many urologists will ask the patient to consider radical prostatectomy or radiation therapy (see below).
Prostate cancer at stage T2 is defined as disease confined to the prostate detected clinically by digital rectal exam and histologically by biopsy. This category is stratified based on the location and extent of disease into T2a (low volume in 1 lobe of the prostate), T2b (present in greater than one half of one lobe) and T2c (disease in both lobes of the prostate). Radical prostatectomy or radiation therapy is recommended if the patient is younger than 75 years old, has no medical contraindications to treatment, and has at least a 10-year life expectancy.
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TABLE 53.5 TNM Classification of Prostate Carcinoma |
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When prostate cancer has progressed locally beyond the capsule of the gland, the stage is T3. Subcategories a, b, and c are assigned based on the location and volume used similarly in stage T2. For T3 disease, therapeutic options include radiation and androgen ablation. With more extensive local advancement, prostate cancer is stage T4. For T4 disease and known metastasis, radiation therapy and androgen ablation therapy are again options.
Treatment of Prostate Cancer
Therapy for prostate cancer therefore may include watchful waiting, surgery, radiation, and/or hormonal manipulation. The selection of therapy is based on many factors including physical examination, PSA level, tumor histology, patient age and comorbidities, and patient preferences. A strategy of watchful waiting may have a place in the management of low volume, low Gleason-grade tumors in an older population of men. This protocol involves frequent PSA measurements, clinical evaluation at regular intervals, and annual prostate biopsy (16). It is important to note that watchful waiting is an active process. It is also unclear with current data exactly which men are suited to this course. Research to more accurately stratify such patients is ongoing.
For localized disease, surgery is an effective option. Radical prostatectomy involves removal of the entire prostate gland and seminal vesicles and reconnection of the bladder to the urethra. This procedure can be done through a lower abdominal incision (radical retropubic prostatectomy), through an incision in the perineum (radical perineal prostatectomy), and, more recently, via an abdominal laparoscopic approach. These procedures require 2 to 5 hours of operative time and a hospital stay from 1 to 3 days on average. A Foley catheter is left in place for 7 to 10 days postoperatively.
As an alternative to surgery, radiation therapy offers an additional curative therapy. This can be delivered with either an external-beam technique or through placement of radioactive seeds into the prostate (brachytherapy). External beam radiation therapy requires daily treatments for 6 to 8 weeks. Brachytherapy is done in the operating room with collaboration between a radiation oncologist and urologist. Fine hollow needles containing the radioactive seeds are placed into the prostate through a grid fixed to the perineum. Preplanned dosimetry dictates the location and placement of the small seeds into the prostate to achieve the maximal effective radiation dose. An overnight hospital stay is most common.
The side effects of therapy for localized disease primarily affect urinary control and sexual function. The prostate is contiguous with the bladder neck and external urethral sphincter. Injury to these structures during surgery or as a result of radiation can lead to varying degrees of urinary incontinence or to scarring and occlusion of the bladder outlet. Many men experience some degree of urinary incontinence after the procedure that requires behavior modification (e.g., the timing and amount of fluid intake) and the use of absorptive pads; this typically lasts up to several months. Occasionally other treatment options are required such as pelvic floor exercises, anticholinergic medications, an artificial urinary sphincter or other surgical procedures depending on the cause and severity of the incontinence (17). The cavernous nerves responsible for erectile function are located along the posterolateral aspect of the prostate gland, and injury to one or both of these nerves can lead to impotence. The incidence of impotence after radical prostatectomy is highly variable and is dependent on a number of factors, including whether nerve-sparing surgery is performed. The majority of men with adequate erectile function preoperatively remain potent after bilateral nerve-sparing surgery (18).
For disease that is locally invasive or metastatic, androgen ablation therapy is often indicated. Many prostate cancers are androgen-dependent, and shutting down the production of testosterone and of its conversion to DHT can suppress production of PSA and the hormone-sensitive cancer cells. This can be accomplished via surgical or medical castration. Medical options for androgen ablation therapy include estrogens, luteinizing hormone-releasing hormone (LHRH) agonists, and antiandrogens. The classic estrogen therapy for prostate cancer is diethylstilbestrol.
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When given in a low dose (1 mg/day), diethylstilbestrol was found to be equivalent to orchiectomy with regard to survival (19). Estrogen therapy, however, can be associated with breast enlargement, water retention, and cardiovascular side effects. Gynecomastia can be avoided by pre-emptive low-dose radiation to the breast, and much of the cardiovascular risk can be reduced with daily aspirin. Nevertheless, diethylstilbestrol therapy for advanced prostate cancer has fallen out of favor despite its efficacy and low cost.
Another avenue for androgen suppression is through use of LHRH agonists. These agents inhibit production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby preventing testosterone production. They have been shown to be as effective as surgical castration. LHRH agonists initially lead to an increase in testosterone production prior to a nadir 3 to 4 weeks after initiation of therapy. This “flare” can cause a worsening of bone pain and other symptoms until testosterone levels fall. In order to avoid this side effect an antiandrogen is given for 2 to 3 weeks. Although here might seem to be additional benefit to complete androgen ablation using combination therapy (a LHRH agonist and an antiandrogen), this has not been demonstrated.
As an alternative to medical hormonal ablation, surgical castration (orchiectomy) is an effective option. This procedure can be performed as an outpatient with a light anesthetic. Complications are uncommon, and testosterone levels fall almost immediately.
Medicalorsurgicalcastrationisgenerallywell-tolerated and are equally effective in reducing PSA and improving performance status in men with advanced prostate cancer. Side effects can sometimes be bothersome, however, and these include osteopenia and osteoporosis, anemia, loss of libido, hot flashes, and asthenia. Hormonal ablation therapy does not prevent or delay progression of prostate cancer, and overall survival is not improved. Roughly 10% of men started on hormonal therapy for metastatic prostate cancer survive less than 6 months. An additional 10% survive longer than 10 years. The remainder fall somewhere between these intervals, with median survival in this group approximately 3 years. The wide range of these numbers is because of great variability in the tumor kinetics and androgen dependence of prostate cancer.
Prostate cancer continues to be an elusive target in terms of diagnosis and cure. The search for improved markers of disease, for more accurate patient stratification, and for effective treatment continues.
Prostatitis/Prostatodynia
Prostatitis is the most common urologic diagnosis in men with lower urinary tract symptoms who are younger than age 50 years, and the third most common urologic diagnosis in men older than 50 years old. The general term prostatitis can be subdivided based on etiology and presentation into four categories as defined by the National Institute of Health (NIH) consensus group on prostatitis in 1995 (20). These include acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (category III), and asymptomatic inflammatory prostatitis (category IV). This schema allows for distinction between identifiable bacterial causes of infection and inflammation in the prostate and symptomatic disorders in the absence of an infectious agent. It is helpful in clarifying diagnosis and therapy selection.
Acute bacterial prostatitis is associated with the acute onset of pain in the perineum, pelvis and lower urinary tract as well as of symptoms of urgency, dysuria, and bladder outlet obstruction. Systemic symptoms of fever, malaise, and nausea are typical. Rectal examination reveals a tender, boggy prostate. If fluctuance is present, an abscess should be suspected and urologic consultation obtained. Vigorous manipulation of the prostate should not be done in the setting of acute prostatitis as this may increase bacteremia. Urine culture most commonly reveals gram-negative bacteria with Escherichia coli the most common (65% to 85%). Pseudomonas, Klebsiella, and Serratiaspecies can also be found. Infection with gram-positive bacteria (e.g., Enterococcus or Staphylococcus aureus) is occasionally seen. Impaired host defense, bacterial virulence, dysfunctional voiding, and reflux into the ejaculatory ducts are some of the presumed mechanisms for development of prostatitis. Antibiotic therapy is indicated for bacterial prostatitis. Trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone is preferred. Therapy is continued for 4 to 12 weeks. In the acute setting, adequate urinary drainage should be established with placement of a urethral catheter or suprapubic catheter if significant obstruction or urinary retention is present. An α-blocker is commonly included to minimize bladder outlet obstruction. Hospital admission for intravenous antibiotic therapy is sometimes necessary.
Chronic bacterial prostatitis produces dysuria and urinary frequency or recurrent UTIs, but generally not the systemic symptoms or the acute onset of pain found in acute bacterial prostatitis. Rectal examination may reveal a tender, swollen prostate, but is often normal. The infection is typically caused by gram-negative bacilli, but Chlamydia infection is also a cause. Similar antibiotic therapy is used as in acute disease. Persistence of symptoms in the face of negative urine cultures should prompt consideration of a chronic pelvic pain syndrome and alternate therapy. For these men, combination therapy with an α-blocker and a nonsteroidal anti-inflammatory drug (NSAID) is customary.
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Specific References*
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