Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms


Frequency

Refers to need to urinate more than usual, commonly taken as need to go back to urinate within 2 h

Urgency

Refers to inability to postpone the urge to urinate

Intermittency

Refers to interrupted stream because patient has to stop and start again several times to finish a single act of urination

Weak urinary stream

May manifest as less amount of urine passage as a function of time or dribbling

Hesitancy and straining

Refers to inability to initiate urine stream despite the urge and patient ends up straining to initiate urination

Nocturia

Refers to waking up from sleep with an urge to urinate

Incomplete bladder emptying

Refers to residual urge after finishing an act of urination or feeling/sensation of not having the bladder completely emptied after finishing urination



LUTS related to different pathologic disease states affect both men and women and are common presenting complaints in both primary care and urologic outpatient offices. The present working theories, however, are focused on the presence of LUTS in men. Bothersome LUTS are highly prevalent in elderly men and require careful clinical attention to minimize potential complications that would impair urologic tract functioning [5]. Multiple population-based studies have shown that the prevalence of LUTS increases with age and that moderate to severe LUTS occur in 25 % of men over the age of 50 years [6, 7]. The pathophysiology of LUTS is often multifactorial. In most cases, obstructive as well as nonobstructive or dynamic factors may contribute to the development of LUTS [5].

One of the major causes of LUTS in middle-aged to elderly men is bladder outflow obstruction (BOO) related to prostate enlargement. It may be caused by a static component which is related to the size of prostate and a dynamic component which is due to the increased alpha-adrenergic smooth muscle tone within the prostate. The prostatic enlargement is most commonly due to benign prostatic hyperplasia (BPH) but may also be from prostatic intraepithelial neoplasia and prostate cancer. LUTS suggestive of BPH are very common in older men, occurring commonly in over one-half of men aged 50 years or older. Patients with LUTS/BPH may present with storage symptoms (e.g., increased daytime frequency, nocturia, urgency) and/or voiding symptoms (e.g., weak force and caliber of stream, hesitancy, terminal dribble) [2]. Figure 11.1 is a schematic flow that summarizes broad etiologic categories of LUTS.

A330006_1_En_11_Fig1_HTML.gif


Fig. 11.1
A schematic flowchart summarizing LUTS and common etiology [2, 5]. BPH benign prostatic hyperplasia, ImC impaired detrusor contractility



Benign Prostatic Hyperplasia


Benign prostatic hyperplasia (BPH) refers to benign enlargement of the prostate gland. In a normal healthy male adult, the prostate gland weighs approximately 20 g. Leissner and colleagues described the average prostate to be 11 g with two standard deviations being 7 and 16 g in one case series of autopsies in healthy young males [8]. Some data suggests that average prostate size increases considerably above 50 years of age. This trend coincides with, and is likely resultant from, an increasing prevalence of BPH and resultant LUTS [9, 10]. Chute and colleagues reported the prevalence BPH and LUTS to range from 26 % to 46 % as men age from the fifth to the eighth decade of life [10]. Another study reported the prevalence to be 19 % when diagnosed using a cutoff of 30 g prostate size and the presence of significant clinical symptoms [11]. In summary, BPH causing clinically significant symptoms is very commonly encountered in primary care practices.

BPH is a histologic diagnosis whereby a glandular hyperplasia is demonstrated along with gross enlargement of the gland as opposed to benign prostate enlargement (BPE), which refers to a clinical diagnosis of an enlarged prostate with clinically assessed benign disease. Paul Abrams emphasizes the use of bladder outlet obstruction (BOO ) until a final dynamic obstructive component can be demonstrated by flow/urodynamic studies along with demonstrated structural enlargement secondary to benign hyperplasia [4]. However, in routine primary care practices, BPH is often diagnosed with significant LUTS in men if prostate-specific antigen (PSA) levels are normal and prostate gland size is enlarged on digital rectal exam (DRE) with benign features.


Evaluation for Suspected BPH


Typically, a man with suspected BPH presents with LUTS (Table 11.1); however, microscopic hematuria, urinary retention, or chronic renal failure can be additional presentations of BPH. LUTS usually have a gradual and progressive course with a vague point of symptom onset. Patients commonly present due to either worsening in the intensity of symptoms leading to lifestyle disturbance or newly associated symptoms including hematuria or urinary retention. More rarely, BPH could be discovered when evaluating someone with chronic kidney disease. Patients with hematuria should be evaluated thoroughly for a full range of etiologies including infection, urologic neoplasm (e.g., bladder, kidney, urothelial), and nephritic syndrome to avoid anchoring diagnostic error in cases where man has a known diagnosis of BPH.

The evaluation of a man for BPH centers on a detailed history and thorough physical examination.


History


The history should focus on the presence or absence of LUTS, the extent of compromise on quality of lifestyle, and the presence of absence of “red flag symptoms” (Table 11.2). Red flag symptoms require prompt evaluation to rule out more serious disorders. A comprehensive review of systems is also very important in deriving a cogent differential diagnosis. Standardized symptom score tools like the American Urological Association Symptom Index (AUA-SI) [17] shown in Table 11.3 or the International Prostate Symptom Score (IPSS) [18] should be used to estimate the severity of symptoms and the impact of these symptoms on quality of life. These symptom scores are based upon symptoms shown in Table 11.1, along with questions specifically aimed at assessing quality of life parameters.


Table 11.2
Red flag symptoms indicating additional broad-based evaluation [1216]





















Hematuria

Evaluate for urolithiasis, urethral stricture, glomerulonephritis, cancers of urinary tract including renal cell cancer, transitional cell cancer, bladder cancer

Chronic perennial pain

Evaluate for chronic prostatitis, proctalgia because of disorders of lower gastrointestinal tract, neuralgia

Neurologic symptoms/deficits of lower extremity

Evaluate for neurogenic bladder, back and spine disorders, or other causes of peripheral nerve issues

Fever, fatigue, dysuria

Evaluate for urinary tract infection, bacterial prostatitis, orchitis, epididymitis, orchid-epididymitis, or other infection elsewhere as suggested by review of systems

Urinary retention

Evaluate for neurogenic bladder, urethral stricture, detrusor-sphincter dyssynergia, and urethral stone. Should also lead to prompt decompression of bladder with Foley’s catheter or suprapubic catheter



Table 11.3
International Prostate Symptom Score (IPSS) [18]





















































































In the past month

Not at all

Less than 1 in 5 times

Less than half of the times

About half the time

More than half the time

Almost always

Your score

1.Incomplete emptying

How often have you had the sensation of not emptying your bladder?

0

1

2

3

4

5
 

2.Frequency

How often have you had to urinate less than every 2 h?

0

1

2

3

4

5
 

3.Intermittency

How often have you found you stopped and started again several times when you urinated?

0

1

2

3

4

5
 

4.Urgency

How often have you found it difficult to postpone urination?

0

1

2

3

4

5
 

5.Weak stream

How often have you had a weak urinary stream?

0

1

2

3

4

5
 

6.Straining

How often have you had to strain to start urination?

0

1

2

3

4

5
 

7.Nocturia

How many times did you typically get up at night to urinate?

0

1

2

3

4

5
 


Add up your scores for total AUA scores: ——

Quality of life due to urinary symptoms: If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? (bold, highlight, or underline)

Delighted Pleased Mostly satisfied Mixed Mostly dissatisfied Unhappy Terrible

Score: mild 1–7, moderate 8–19, severe 20–35

The standardized tools like AUA-SI and IPSS can provide a method of quantification to be followed longitudinally to guide clinicians in the initiation and monitoring of symptomatic therapy. The AUA-SI is shown in Fig. 11.2 and IPSS in Table 11.3, respectively. Voiding diaries can also be helpful in charting symptom progress.

A330006_1_En_11_Fig2_HTML.gif


Fig. 11.2
American Urological Association Symptom Index (AUA-SI) [17]


Physical Examination


The physical examination should be complete, including evaluations of the head and neck and pulmonary, cardiac, abdominal, and pelvic systems and a detailed assessment to evaluate for lymphadenopathy. The genital (penile and scrotal) examination should detect any gross abnormalities or lesions, and the digital rectal examination (DRE) should be conducted thoroughly as detailed below.

Digital rectal examination (DRE) is one of the most important, readily available, cost-effective tools for prostate evaluation. The prostate gland is walnut-shaped structure located at the base of the urinary bladder; the apex is caudal and the base cranial as shown above. Normally, it weighs approximately 20 g and measures approximately 4 cm in transverse diameter, 3 cm in vertical, and 2 cm in anteroposterior diameter. It has an anterior surface, a posterior surface, and two inferolateral surfaces.

The DRE can be performed in several different positions, most commonly the left lateral decubitus and the knee-elbow positions. In one example, the patient may lie on the examination table in the left lateral decubitus position when the finger of the examiner is inserted in the rectum to palpate the prostate. The knee-elbow position allows the patient to lean over the examination table using elbows and bends his knees to allow for the examiner to insert the finger into rectum. The examiner should palpate for appropriate anal sphincter tone, generalized characteristics of the anal wall mucosa, and anteriorly the prostate including size, consistency, symmetry of the lobes, median sulcus, frank masses, indurations, nodules, and tenderness/bogginess. Understanding these characteristics while performing a “blind” examination can assist in differentiating among normal findings, benign enlargement, prostatitis, and prostate cancer (Table 11.4).


Table 11.4
DRE prostate features concerning of disease processes other than benign prostate disease [1214]












Prostatitis

Boggy, moderately to severely tender, may or may not be enlarged

Prostate cancer

Indurations, nodules, hard consistency, mass, asymmetry, distortion of median sulcus, commonly non-tender

The size of the prostate can be estimated by using the “finger pad sweep” technique. Essentially, one finger pad sweep (the estimated surface area of the palmar surface of the index finger) over the prostate gland measures to be approximately 15–20 g (the normal weight of the prostate). Additional finger pad sweeps in both lateral and vertical directions should be added to estimate the total prostate size.

Another method of estimating and documenting prostate gland volume is to define one finger pad sweep as being a normal-sized gland; two finger pad sweeps would be estimated as double the normal size or “+2”; three finger pad sweeps estimated as triple the normal size or “+3”; etc. Another schematic used by primary care clinicians is estimating if the examiner can reach and feel both upper and lateral limits of the prostate with a finger sweep, then it is less than 30 g (+1 to +2 size), whereas if the examiner can reach the lateral limits only and not the vertical limits, then it is between 30 and 50 g (+2 to +3), while if both lateral and vertical limits are not reachable, then prostate volume is likely more than 50 g (more than +3) in size. It is recommended that an examiner use one technique and one system of documentation to maintain consistency across examinations.

The yield of the DRE is variable depending upon the indication for examination and the experience of the examiner. Although its importance as a screening tool for the diagnosis of prostate and colorectal cancer has been questioned [1214], it is very useful in evaluating a man who presents with complaints related to urogenital tract. Although both left lateral and knee-elbow positions as described above have been reported to be comparable in patient discomfort, embarrassment, and completeness of examination [19], considerable inter-rater variability exists among examiners [20], as more experienced examiners are more likely to detect a significant abnormality [21].


Workup and Investigation


The extent of laboratory testing and radiographic imaging depends upon the data from the history and physical examination as described above. The AUA recommends routine baseline and follow-up evaluations of the PSA and urinalysis in patients with symptoms consistent with BPH and/or LUTS. It is reasonable to obtain baseline and follow-up serum blood urea nitrogen (BUN) and creatinine levels if symptoms have been insidious with gradual worsening or in cases of hematuria or urinary retention.

The urinalysis can provide a broad range of information to aid in confirming or ruling out a urinary tract infection (UTI ); defining the presence of blood, protein, or glucose; or raising the possibility of other closely related urogenital conditions via the presence of crystals, casts, sediment, or leukocytes. Table 11.5 describes macroscopic features of the urinalysis and commonly associated conditions with these symptoms.


Table 11.5
Macroscopic features and commonly associated conditions [15, 22]


















Odor

•Ammonia-like

•Foul, offensive

•Sweet

•Fruity

•Maple syrup-like

(Urea-splitting bacteria)

Old specimen, pus, or inflammation

Glucose

Ketones

Maple syrup urine disease

Color

•Colorless

•Deep yellow

•Yellow green

•Red

•Brownish red

•Brownish black

Diluted urine

Concentrated urine, riboflavin

Bilirubin/biliverdin

Blood/hemoglobin

Acidified blood (acute GN)

Homogentisic acid (melanin)

Turbidity

•Typically cells or crystals

•Cellular elements and bacteria will clear by centrifugation

•Crystals dissolved by a variety of methods (acid or base)

•Microscopic examination will determine which is present

When present, a UTI should be appropriately treated before initiating chronic medical therapy for LUTS. Determination of a UTI can be straightforward in the presence of new onset dysuria, fever, and suprapubic tenderness; however, in many cases this may be complex and challenging to differentiate when caring for men with a history of chronic LUTS. In such cases, multiple findings on urinalysis can help to make diagnosis of UTI. Table 11.6 summarizes the validity and reliability of urinalysis parameters for the diagnosis of UTI [22].


Table 11.6
Summary of the validity and reliability urinalysis parameters for diagnosis of UTI [15, 22]






































































Results

Sensitivity

Specificity

PPV

NPV

Positive leukocyte esterase

72–97

41–86

43–56

82–91

Presence of nitrites

19–48

92–100

50–83

70–88

Positive leukocyte esterase or presence of nitrites

46–100

42–98

52–68

78–98

≥3+ protein

63–83

50–53

53

82

≥1+ blood

68–92

42–46

51

88

Any of the above abnormalities

94–100

14–26

44

100

> 5 WBCs per HPF

90–96

47–50

56–59

83–95

> 5 RBCs per HPF

18–44

88–89

27

82

Bacteria (any amount)

46–58

89–94

54–88

77–86


All numerical values are expressed in percentage

UTI urinary tract infection, PPV positive predictive value, NPV negative predictive value, WBC white blood cells, RBC red blood cells

The urine culture should be used to aid the determination of a proven UTI and to guide antibiotic therapy in men or nonpregnant patients (Fig. 11.3). A positive urine culture should always be treated in the presence of fever, fatigue, suprapubic pain, and/or flank tenderness [15]. In the absence of these classic features, it is recommended that positive urine culture be treated at least at the onset of medical therapy for LUTS or during a sudden worsening of symptoms.

A330006_1_En_11_Fig3_HTML.gif


Fig. 11.3
Schematic flow diagram of positive urine culture based upon Infectious Disease Society of America (IDSA) guidelines [15]. LUTS lower urinary tract symptoms, UA urinalysis, CFU colony forming units, HPF high-powered field

Serum prostate-specific antigen (PSA) levels are helpful in the initial workup and is routinely recommended by the AUA in all cases of LUTS and suspected BPH. Elevated levels (however, arbitrarily defined) still should raise suspicion for prostate cancer; however, these values should be interpreted with caution as elevated PSA levels may simply be the results of an increase in the volume of the prostate. Some studies have suggested a log-linear relationship between serum PSA levels and prostate volume [23, 24]. PSA density, which accounts for PSA ng/ml per gram of prostate volume, can be useful when determining appropriate or inappropriate elevations of PSA. Free PSA levels have been shown to have a better correlation with prostate volume than with predicting cancer risk [25]. In such cases, it is suggested that primary care clinicians consult a urologist to seek expert opinion on further workup and evaluation. Please see Chap. 14 for a further detailed discussion on abnormal PSA levels and prostate cancer risk.


Evaluation of Extent of Bladder Outlet Obstruction


Chronic bladder outlet obstruction may be suggested in men by obstructive LUTS and storage symptoms due to BPH, yet such symptoms do not quantify the extent of BOO. The AUA symptom score or the IPSS, both highlighted above, may provide further insight and help guide the goals of therapy [17]. The initial evaluation of the man with BPH and/or LUTS should assess the extent of BOO, which can be determined via post-void residual (PVR) volume, noninvasive uroflowmetry (UFM), or full urodynamic studies (UDS) for cystometrography (CMG).


Post-Void Residual


It is recommended by the European Association of Urology (EAU) for routine initial evaluation and monitoring of success of therapy [26]. It is a simple measure that can be obtained in the office setting via post-void urinary catheterization or ultrasonography. Post-void urinary catheterization is simple and cost-effective yet carries a risk of patient discomfort, embarrassment, and infection. Ultrasonography is also a very facile method to relatively assess post-void residual volume. While conventional ultrasonography requires radiologic training and expertise, bladder scanners are small handheld devices that require minimal training and expertise and can be easily performed in the office setting. Normal men without significant BOO usually have a PVR less than 12 ml of urine [16]. A significant controversy exists on the benefit of using PVR as a sole parameter to select surgical candidates [27]; hence, a full clinical picture, response to therapy, availability of procedural skills, and patient preference should all play a role when selecting patients for surgical therapy.


Noninvasive Uroflowmetry for Maximal Flow Cystometrography


CMG with real-time urodynamic pressure flow studies is considered to be the gold standard for examining voiding function [28]. This study can assess the static component of BOO as well as real-time bladder decompensation. This method, however, is invasive and involves a urinary catheter, rectal catheter, and infusion of fluid into the bladder. While cumbersome, this study is usually performed by urologists once a patient is refractory to treatment or has indications of bladder decompensation. Noninvasive UFM for maximal urine flow is, on the other hand, a relatively simple and harmless.

Since McConell’s advocacy for the development of noninvasive parameters for above said purpose in 1994 [29], multiple studies [30, 31] have shown data in favor of using these measures. This leads to EAU recommendation for routine use of uroflowmetry in the management of LUTS, BPH, and BOO among men. Specifically for uroflowmetry to be useful, EAU standards require a pre-void volume of 250 ml with voided volume of at least 150 ml to make it to adequate uroflow study [26]. A maximal urinary flow rate of greater than 15 ml/s for a minimum voided volume of 150 ml has high negative predictive value for ruling clinically signi ficant BOO [32]. A maximal urinary flow rate of less than 10 ml/s predicts better surgical outcome in BPH [31].


Treatment


Treatment for BPH causing significant LUTS is directed toward treating bothersome urinary symptoms to improve quality of life and preventing complications by early detection, behavioral modification, medical therapy, or surgical intervention. In the absence of significant BOO or any complication, initiation of medical therapy should be a shared decision between the patient and the physician to balance the quality of life and potential adverse effects from medications. The symptom severity of LUTS can easily be tracked semiquantitatively with an added quality of life question by using AUA symptoms index described above in the evaluation section [33].


Behavioral Modification


Behavioral modification should be considered when surgical intervention is not indicated and medical therapy is thought to be inappropriate either because of mild symptoms or side effects of the medications. Behavioral modification has been shown to be better than watchful waiting in mild (IPSS score less than 8) [34]. Examples include limiting caffeinated drinks, limiting fluid intake later in the day prior to bedtime, and performing timed voids to maximize bladder emptying.


Medical Therapy


Medical therapy is the mainstay of treatment in the absence of severe symptoms that indicate emergent evaluation, bladder outlet obstruction, and bladder decompensation. Medical therapy with a single agent should be the initial approach, yet some men may require combination therapy to adequate control LUTS and improve quality of life.

Alpha1 blockers are the cornerstone of medical monotherapy for LUTS due to BPH. One large meta-analysis that combined RCTs and some comparative studies with over 7000 patients found a 30–40 % reduction of IPSS scores as compared to placebo [35]. The same study estimated a 16–25 % increase in maximal urinary flow rates as well. There are very few head-to-head trials [36, 37] to compare the efficacy of one alpha-1 blockers over another, as they are assumed to have similar efficacy yet may differ slightly in their adverse effect profile. Newer agents including alfuzosin and silodosin may have a slight advantage in efficacy yet also may be cost-prohibitive with certain healthcare plans. Standard dosing of alpha-1 blockers is summarized in Table 11.7, while Table 11.8 compares the side effect profile.


Table 11.7
Summary of routine dosing for alpha-1 blockers [38]





















Terazosin

Dosage range is 1–10 mg PO QHS, starting with 1 mg, is titrated gradually to desired response over 7–8-week period for immediate release formulation while around 4-week period for longer acting formulation

Doxazosin

Dosage range is 1–8 mg PO QHS, starting with 1 mg, is titrated gradually to desired response over 7–8-week period for immediate release formulation while around 4-week period for longer acting formulation

Alfuzosin

Dose at 10 mg PO QHS initial and maintenance, no titration needed

Tamsulosin

Dose at 0.4 mg PO QHS initial and maintenance, may increase to 0.8 mg PO QHS if desired response not achieved in 2 weeks

Silodosin

Dose at 8 mg PO QHS initial and maintenance, no titration needed



Table 11.8
Common adverse reaction profile of alpha-blockers [3942]









































 
Terazosin

Doxazosin

Alfuzosin

Tamsulosin

Silodosin

Hypotension

+++

+++

++

+

+

Ejaculatory dysfunction

+

+


+++

++

Headache, dizziness, syncope

++

++

++

+

+

Others

Other adverse reactions like floppy iris syndrome during cataract, etc. are equally distributed among these medications. Prazosin, not mentioned above, has cardiac adverse events and generally not used for BPH/LUTS


The number of + signs indicates the commonality of occurrence of adverse events

Five-alpha (5α)-reductase inhibitors reduce prostate size slowly over months when taken regularly and in most cases reduce serum PSA values [43]. Although not considered to be as effective as alpha-1 blockers, they can be considered as initial monotherapy in cases where alpha-1 blockers are not well tolerated or contraindicated (e.g., those patients who will undergo ophthalmologic surgery due to risk of intraoperative floppy iris syndrome). Finasteride is dosed at 5 mg once daily, while dutasteride is ten times more potent and dosed at only 0.5 mg once daily. Since there is no risk of orthostatic hypotension with this class of medication, no titration is needed. Both finasteride and dutasteride are comparable in their efficacy and side effect profile and are FDA approved for treatment of BPH [43]. By convention, after a patient has been taking a 5-alpha-reductase inhibitor for 6 months, their PSA value should be doubled when followed.

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Jul 30, 2017 | Posted by in ABDOMINAL MEDICINE | Comments Off on Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

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