The goal of work-up of lower urinary tract symptoms is to establish the severity and cause of lower urinary tract symptoms and to predict with certainty which patients will respond to which treatments. Clinical guidelines exist to guide urologists in decision-making. All patients need a medical history with a validated symptom score, a physical examination, and a urinalysis. Prostate-specific antigen, postvoid urine residual, and peak urine flow rate provide additional information at little cost. For more invasive testing high-level data are lacking and guidelines defer to the urologist. Even the most extensive work-up is imperfect, and thus the attempt to balance costs with benefits of invasive testing.
Key points
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The focus of the initial evaluation of LUTS should be to assess symptomatology and rule out etiologies other than prostatic enlargement.
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Algorithms for the evaluation of LUTS rely largely on expert opinion.
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All patients presenting with LUTS should undergo a medical history, physical examination with DRE, and urinalysis.
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Data regarding the benefits of invasive testing including pressure-flow studies, prostate ultrasound, and endoscopy are lacking and mixed.
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The extent of the diagnostic work-up should depend on symptom severity and planned intervention.
Introduction
Benign prostatic hyperplasia (BPH) is a histologic diagnosis defined by proliferation of benign prostatic stromal and epithelial tissue. It can lead to benign prostatic enlargement and subsequent bladder outlet obstruction and/or lower urinary tract symptoms (LUTS). Most patients with BPH presenting to their urologist come with a chief complaint of LUTS. The goal of the initial work-up is two-fold: assess the severity of the patient’s symptoms and rule out alternative etiologies. Broadly speaking, the extent of the work-up should depend on the extent of symptoms, the suspected cause, and the planned therapy. Fortunately non-BPH causes of LUTS are usually easily identified by history; physical examination; and inexpensive, noninvasive testing. For patients in whom the diagnosis remains unclear after initial work-up, additional diagnostic testing may be helpful.
Given that BPH is a progressive disease, a secondary goal is to identify patients at risk of rapid symptomatic progression and of complications of BPH, because these patients may decide to pursue more aggressive therapies early on. Complications of BPH include urinary retention, gross hematuria, recurrent urinary tract infection (UTI), bladder stones, and bladder decompensation (diverticula, decreased contractility, hypercontractility, hypertrophy with increased voiding pressures, and obstructive nephropathy). Patients who present with complications of BPH are subject to a different diagnostic algorithm than those presenting with isolated LUTS.
Introduction
Benign prostatic hyperplasia (BPH) is a histologic diagnosis defined by proliferation of benign prostatic stromal and epithelial tissue. It can lead to benign prostatic enlargement and subsequent bladder outlet obstruction and/or lower urinary tract symptoms (LUTS). Most patients with BPH presenting to their urologist come with a chief complaint of LUTS. The goal of the initial work-up is two-fold: assess the severity of the patient’s symptoms and rule out alternative etiologies. Broadly speaking, the extent of the work-up should depend on the extent of symptoms, the suspected cause, and the planned therapy. Fortunately non-BPH causes of LUTS are usually easily identified by history; physical examination; and inexpensive, noninvasive testing. For patients in whom the diagnosis remains unclear after initial work-up, additional diagnostic testing may be helpful.
Given that BPH is a progressive disease, a secondary goal is to identify patients at risk of rapid symptomatic progression and of complications of BPH, because these patients may decide to pursue more aggressive therapies early on. Complications of BPH include urinary retention, gross hematuria, recurrent urinary tract infection (UTI), bladder stones, and bladder decompensation (diverticula, decreased contractility, hypercontractility, hypertrophy with increased voiding pressures, and obstructive nephropathy). Patients who present with complications of BPH are subject to a different diagnostic algorithm than those presenting with isolated LUTS.
Patient history
Symptom Score
A validated assessment of LUTS is uniformly recommended in the initial work-up of LUTS, both as an objective assessment of symptoms and a quantifiable metric by which to measure efficacy of treatment. The International Prostate Symptom Score (IPSS) is a scoring system originally developed by the American Urologic Association (AUA), and is now the standard assessment in the United States. In this questionnaire, seven voiding symptoms are rated on a five-point Likert scale, followed by a quality of life score. Symptom scores are summed and classified as mild (0–7), moderate (8–19), or severe (20–35). Although the IPSS is internally consistent and reliable, there are certainly limitations. First and foremost IPSS does not diagnose BPH and does not determine treatment, which is guided primarily by quality of life score and complications of BPH. The validity of the self-administered IPSS varies across socioeconomic class. Other validated scoring systems do exist (eg, Danish Prostate Symptom Score, BPH Impact Index); however, these are less ubiquitous in North America.
Frequency-Volume Charts
Frequency-volume charts, or voiding diaries, are simple to complete, inexpensive, and can provide useful objective insights into a patient’s voiding history. These can serve as an adjunct to the IPSS, and tend to be more accurate that patient recall. Although there is no standard diary protocol data suggest that a voiding diary should last at least 3 days, with the goal of being long enough to avoid sampling error but short enough to optimize compliance. The AUA guideline on the management of BPH suggests that frequency-volume charts be used in patients with nocturia as the dominant symptom to help identify patients with isolated nocturnal polyuria or excessive fluid intake. Polyuria, defined in the AUA guidelines as urine output greater than 3 L daily, or nocturnal polyuria, defined as more than one-third of urine output during the night, should be approached initially with lifestyle modification.
Additional History
In addition to an assessment of voiding symptoms, the patient interview must include a directed history regarding alternative causes of voiding dysfunction. Specific additional areas to discuss when evaluating a man with LUTS include a history of UTI, hematuria, diabetes, spine and neurologic disease, prior urinary retention, and sleep disorders including sleep apnea. Any prior urologic history including urinary catheterization and instrumentation should be elucidated, as should risk factors for urethral stricture disease including prior trauma or sexually transmitted infections. A smoking history is important to assess the risk for bladder cancer and because nicotine is a bladder irritant. Medications and supplements should be reviewed in detail, with particular attention to medications that increase outflow resistance (eg, α-sympathomimetic agents) or reduce bladder contractility (eg, anticholinergics).
Physical examination
The physical examination of patients with LUTS suspected to be caused by BPH should include the following:
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Abdominal examination: to evaluate for a palpably distended bladder
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Genitourinary examination: evaluate meatal stenosis, phimosis, urethral discharge, lichen sclerosis (which can be associated with stricture disease), and urethral mass
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Focused neurologic examination: including motor and sensory function of the perineum and lower limbs
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Digital rectal examination (DRE): to evaluate sphincter tone, prostate nodules, tenderness or bogginess of the prostate, rectal masses, and to give an estimate of prostate size
Digital estimation of prostate size is notoriously inaccurate, although one can generally distinguish prostates less than 50 g from those greater than 50 g. Training with a dedicated model can improve accuracy. Moreover, prostate size does not correlate well with symptom severity, degree of urodynamic obstruction, or treatment outcomes. Still, given that gland size portends a greater risk of BPH progression and may guide pharmacologic or surgical approach, a general estimate of size based on DRE can be valuable.
Imaging and additional testing
Some basic, noninvasive testing is recommended in all patients. Urologists may pursue additional imaging and additional testing in the work-up of LUTS when invasive therapies are being considered, or where there is suspicion that the patients’ symptoms are not caused by BPH.
Urine Studies
Urinalysis with urine microscopy is recommended for all men presenting with LUTS. Although serious urinary tract pathology is rarely detected, urinalysis is an innocuous, inexpensive, simple to perform test, and the benefits clearly outweigh the harm. It may reveal the following:
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UTI: Detecting UTI is important in men with LUTS for two reasons. UTI can mimic LUTS, and a symptom assessment should be repeated once the UTI is treated. Moreover, recurrent UTIs in patients with BPH and bladder outlet obstruction is an indication to pursue invasive treatments, even in the setting of minimal LUTS.
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Glucosuria, proteinuria: Occasionally, diabetes is detected by the presence of glucose in the urine. Additionally, protein in the urine may be an early indicator of medical renal disease. Polyuria caused by either diabetes or a renal concentrating defect may mimic LUTS caused by BPH.
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Hematuria: Detection of microhematuria prompts a microhematuria work-up, which may reveal alternative etiologies of LUTS including urothelial cancer or, more rarely, distal ureteral stones. Even without microhematuria, consideration may be given to urine cytology in men with severe irritable symptoms and dysuria, particularly if there is a history of smoking. Bladder cancer and carcinoma in situ notoriously mimics the storage symptoms of BPH, and a missed diagnosis is potentially catastrophic.
Serum Creatinine
Historically, measurement of serum creatinine has been recommended in the initial work-up of BPH to rule out obstructive uropathy. Because the incidence of baseline renal insufficiency seems to be no higher in the BPH population than the population at large, the most recent iteration of the AUA guidelines no longer recommends obtaining serum creatinine in patients whose initial work-up reveals LUTS only. Analysis of the MTOPS trial data shows that the risk of developing de novo renal failure in men with LUTS is minimal (<1%). A model of shared decision making is suggested when it comes to initial testing beyond urinalysis, with the thought that progression of BPH will be detected with yearly re-evaluation of symptoms. For patients with LUTS who have a history of hypertension or diabetes, there does seem to be an increased risk for renal disease and physicians should consider obtaining serum creatinine in these patients. Moreover, given that patients with elevated serum creatinine suffer more perioperative complications, it is reasonable to check creatinine in all patients before surgical intervention.
Prostate-Specific Antigen
Prostate cancer may present with LUTS by producing bladder outlet obstruction similar to benign prostatic enlargement. In men with a life expectancy of at least 10 years, a diagnosis of prostate cancer may well alter the treatment of their voiding symptoms. Moreover, LUTS caused by obstruction from prostate cancer may respond differently to standard treatment approaches. Prostate-specific antigen (PSA) testing should be offered to patients who have at least a 10-year life expectancy, and for whom a diagnosis of prostate cancer would change management. As with all patients being offered PSA testing for prostate cancer screening, a thorough discussion of limitations of the test, alternative causes of PSA elevation, and the risks and benefits of prostate biopsy should be held.
Given that BPH is a source of elevated PSA, there is significant overlap between the serum PSA values of men with BPH and with early prostate cancer; more than one-quarter of patients with histologically proven BPH have a serum PSA value greater than 4.0 ng/mL. PSA velocity, percent free PSA, and, for patients who undergo transrectal ultrasound, PSA density may help improve the specificity of PSA in detecting prostate cancer in men with BPH.
In the absence of malignancy, PSA is a useful surrogate of prostate size. In a study of nearly 4500 men with BPH and without prostate cancer Roehrborn and colleagues demonstrated an age-dependent, log-linear relationship between PSA and prostate volume, with a steeper rise in prostate volume per increase in PSA as men get older ( Fig. 1 ). Their data reveal that age-specific thresholds for detecting men with prostate glands exceeding 30 mL (within the realm of responsiveness to 5α-reductase inhibitors) are greater than or equal to 1.3 ng/mL, greater than or equal to 1.5 ng/mL, and greater than or equal to 1.7 ng/mL in men with BPH in their 50s, 60s, and 70s, respectively. This relationship was confirmed by a retrospective analysis of more than 1800 Dutch patients that shows that 89% of men with PSA greater than 1.5 ng/mL have a prostate volume greater than 30 mL, and by the MTOPS data, which show that PSA greater than 1.5 ng/mL represents a prostate volume of greater than or equal to 30 mL regardless of age.
Evidence also suggests that PSA can predict the risk of BPH progression, the likelihood of response to 5α-reductase inhibitors, the need for surgical intervention, and the risk of urinary retention. Urologists should note that in men with BPH already treated with 5α-reductase inhibitors PSA values can be reduced by 40% to 50% after 6 months of therapy and may be difficult to interpret in the absence of a pretreatment baseline. For this reason, urologists must obtain a baseline PSA before initiating therapy with 5α-reductase inhibitors.
Postvoid Residual Urine Volume
Postvoid residual (PVR) urine volumes are typically assessed by noninvasive transabdominal ultrasound. This is another rapid, noninvasive, inexpensive test with few downsides, although retest measurement variability yields repeated measurements prudent. Note that alternative sources of pelvic fluid, such as ascites or a reservoir for an inflatable penile prosthesis, fool the machine. In patients with bladder outlet obstruction caused by BPH, residual urine is useful to assess and follow the degree of using. PVR cannot distinguish between obstructive urinary retention and myogenic or neurogenic urinary retention, but can to some extent distinguish obstruction from isolated overactive bladder, because patients with isolated overactive bladder should have low residual urines.
A precise definition for urinary retention has been notoriously elusive, and as such a threshold PVR has never been agreed on. There is a surprising lack of clear correlation between elevated PVR and episodes of acute urinary retention (AUR) or the need for invasive treatment. In their study of nearly 1000 patients with BPH treated with watchful waiting or α-blockers, Mochtar and colleagues found PVR to be unhelpful in predicting the risk of AUR, and only patients with PVRs greater than 300 mL were at increased risk of requiring invasive therapy. Conversely, Klarskov and colleagues found that of men with AUR, a PVR greater than 500 mL increased the risk of recurrent AUR by a factor of 3.6. In men with lesser residual volumes, it has been difficult to show a relation between PVR and any urinary outcome. As noted by Kaplan and colleagues, the lack of correlation with PVR may merely represent the exclusion of men in many studies with PVR greater than 150 mL. There are little data to suggest that elevated PVR should prompt upper tract imaging to evaluate hydronephrosis, because hydronephrosis is thought to result more from ureteral obstruction from BPH and/or from a low-compliance bladder.
Peak Urine Flow Rate
Like residual volume, flow rate is a measure of bladder and outlet function, and cannot definitively distinguish between the two. It is generally accepted that a maximum flow rate less than 10 mL/s indicates a high probability of obstruction, whereas a flow rate greater than 15 mL/s indicates a low probability. Table 1 outlines general maximum flow rate values and their implications; however, flow rates must be interpreted in the setting of voided volume and age. For men with suspected bladder outlet obstruction, the International Continence Society has published a nomogram that groups men into three categories (obstructed, unobstructed, and equivocal) based on maximum flow rate and maximum detrusor pressure, although this requires pressure-flow studies for evaluation ( Fig. 2 ). The Olmsted Community study used a cutoff of 12 mL/s, and showed that men with peak urine flow rates below this had nearly three times the risk of surgery and AUR than those with higher flow rates. Conversely, in the MTOPS study a peak flow rate less than 10.6 mL per second was not predictive of AUR in placebo-treated subjects ( Fig. 3 ).
| Q max (mL/s) | Implication |
|---|---|
| <10 | Likely obstructed |
| 10–15 | Indeterminate |
| >15 | Likely unobstructed |
| 20–25 | Normal |
Related posts:
The Epidemiology of Benign Prostatic Hyperplasia Associated with Lower Urinary Tract Symptoms
Alpha-blockers for the Treatment of Benign Prostatic Hyperplasia
Antimuscarinics, β-3 Agonists, and Phosphodiesterase Inhibitors in the Treatment of Male Lower Urinary Tract Symptoms
Bipolar, Monopolar, Photovaporization of the Prostate, or Holmium Laser Enucleation of the Prostate
Robotic-Assisted Simple Prostatectomy
Sexual Side Effects of Medical and Surgical Benign Prostatic Hyperplasia Treatments
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