Abstract
Diagnostic work-up of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia aims to detect/quantify the three disease components (LUTS, benign prostatic enlargement, and benign prostatic obstruction (BPO)), estimate disease progression, and identify alternative diseases since LUTS is multifactorial. Standard tests include: (1) medical history, (2) symptom questionnaires, e.g., International Prostate Symptom Score, (3) physical examination (including digital-rectal examination), (4) urinalysis, (5) blood analysis with prostate-specific antigen if a diagnosis of prostate cancer will change management or if it assists in the treatment and/or decision making process, (6) post-void residual (PVR) measurement, and (7) uroflowmetry prior to any active treatment. In selected men, the following tests are recommended: voiding diary (for those with nocturia and/or storage symptoms), imaging of the kidneys (in cases with high PVR, hematuria, or urolithiasis history) or prostate (to choose appropriate drugs), urethro-cystoscopy (in men with suspected bladder/urethral pathology and before minimally invasive surgery), and pressure-flow studies. Novel approaches have been developed to quickly, noninvasively, and safely detect BPO; promising tests are ultrasound measurements of intravesical prostatic protrusion or detrusor wall thickness.
Keywords
Benign prostatic hyperplasia, Bladder outlet obstruction, Diagnosis, Lower urinary tract symptoms, Prostate
Introduction
Benign prostatic hyperplasia (BPH) is a term that describes the microscopic changes in the prostate, which are highly prevalent in elderly men, and are characterized by benign growth of epithelial, muscular, and/or fibrotic cells. Direct proof of microscopic BPH by prostate biopsies is restricted to those men who need discrimination between BPH, prostate carcinoma, or prostatitis but, despite that, is not necessary during routine assessment. BPH may cause lower urinary tract symptoms (LUTS), benign prostatic enlargement (BPE), and/or benign prostatic obstruction (BPO). However, not all patients with BPH develop all these three components and presence of one component is not necessarily associated with the development of the others ( Fig. 6.1 ).
Diagnostic work-up of LUTS/BPH has two principal objectives [ , ]: (1) specify the individual clinical profile of a man with detection and quantification of the three main components (LUTS, BPE, BPO) and to estimate the risk of disease progression and (2) identify alternative diseases since the origin of male LUTS is multifactorial. Accordingly, the work-up aims to exclude other causes of prostatic enlargement, LUTS, or bladder outlet obstruction (BOO) other than those related to BPH; to provide information at baseline about the presence/severity of the three BPH components; and to evaluate potential BPH-associated complications of the lower and/or upper urinary tract directly or indirectly related to BOO/BPO which all exclude conservative treatment later ( Tables 6.1 and 6.2 ). The various available tests (recommended and optional) are therefore useful for diagnosing, monitoring, and assessing disease progression risk, treatment planning, and prediction of treatment outcome [ , ]. After baseline investigations, the physician should be able to determine if and how the patient should be treated.
| Recommended (In All Patients) | Optional (In Selected Patients) | Not Recommended (May be Indicated in Selected Patients for Further Assessment of Pathological Findings) |
|---|---|---|
|
|
|
| BPH-Associated Complications | Test |
|---|---|
| Urinary tract infections | History, urine analysis |
| Hematuria | History, urine analysis |
| PVR urine | History, PVR urine measurement (ultrasound) |
| Urinary retention (> 300 mL) | History, PVR urine measurement (ultrasound) |
| Bladder stones/diverticula | Bladder ultrasound |
| Hydronephrosis | Serum creatinine measurement, renal ultrasound |
| Renal insufficiency | Serum-creatinine level/clearance measurement |
Diagnostic Workup of LUTS/BPH
Standard Diagnostic Tests
History
The assessment of the medical history of patients has been always considered very important [ ]. According to the EAU Guidelines on Nonneurogenic Male LUTS [ , ], a complete medical history must always be taken from men with LUTS (Level of Evidence (LE) 4; Grade of Recommendation (GR) A; Fig. 6.2 ). It aims to identify potential LUTS causes, relevant comorbidities, current medication, lifestyle habits, and emotional or psychological factors. Symptoms and available therapeutic options should be discussed from the patient’s perspective, and the patient should be reassured that presence of LUTS is not indicative of a higher prostate cancer (PCa) prevalence compared to asymptomatic men [ , ]. The urological history should be supplemented by a self-completed validated symptom questionnaire that objectifies and quantifies LUTS; a voiding diary especially if patients with nocturia and/or storage symptoms are assessed; and a validated symptom questionnaire such as the International Index for Erectile Function (IIEF) assessing sexual function [ , ].
Symptom Questionnaires
A validated symptom questionnaire should always be used [ ]. According to the EAU Guidelines on Non-neurogenic Male LUTS [ , ], a validated symptom score questionnaire (incl. the evaluation of quality of life (QoL)) should be used for the routine assessment of male LUTS in all patients at baseline and for re-evaluation during and/or after treatment to objectively quantify treatment effects (LE 3; GR B; Fig. 6.2 ). Despite the fact that symptom score questionnaires are not age-, gender-, or disease-specific [ ], many are available for routine use and able to qualify/quantify LUTS, identify predominance of voiding or storage LUTS, and sensitively detect changes during treatment [ ].
The most widely used questionnaire worldwide is the International Prostate Symptom Score (IPSS) questionnaire ( Fig. 6.3 ). It is a validated 8-item tool consisting of seven symptom questions and one question for QoL assessment; symptom questions and the QoL question are evaluated separately. The IPSS-questionnaire produces reliable, consistent, and stable results [ ]. It should be noted once more that the IPSS-questionnaire is also not age-, gender-, or disease-specific and thus can only be used to evaluate LUTS independent of the underlying disease. The IPSS questionnaire has the disadvantage that questions concerning urinary incontinence or postmicturition symptoms are missing and only global QoL can be measured—instead of the assessment of bother caused by each individual symptom [ , ].
Symptom questions of the IPSS questionnaire can be divided into storage symptoms (IPSS questions 2, 4, and 7) and voiding symptoms (IPSS questions 1, 3, 5, and 6). For each question, the patient can choose between six answers (score 0–5) and indicate how frequently this symptom has appeared on average during a 24 h period during the last 4 weeks. Total IPSS can range between 0 and 35 points, thereby documenting a span between no symptoms (score 0) and maximum amount of symptoms (score 35). Scores between 1 and 7 points indicate “mild,” between 8 and 19 points “moderate,” and between 20 and 35 points “severe” symptom severity. Medical or surgical treatment should be considered in men with “moderate to severe” LUTS (symptom scores > 7).
The 8th IPSS question evaluates how the patient would feel if LUTS remained for the rest of his life; the patient has seven answers to express symptom bother (scores 0–6), thereby documenting a span between excellent (answer 0) and very poor QoL (answer 6). Storage symptoms are usually associated with greater bother than voiding symptoms. Greater bother (answers 3–6) implies a need for treatment. During treatment, including watchful waiting and conservative treatment, a decrease of at least 3 points in the symptom questions (score of questions 1–7) can be realized by the patient as symptom relief and is usually associated with improvement of QoL and symptom bother (question 8).
Frequency Volume Charts and Bladder Diaries
The frequency-volume chart (FVC) is a patient-documented record of the time and volume of each void within a 24 h period. A bladder diary is a similar but more distinguished record including extra data such as volume and type of fluid intake, grading of urgency before voiding, incontinence episodes, and pad use [ ]. According to the EAU Guidelines on Non-neurogenic Male LUTS [ , ], FVCs or bladder diaries should have a balanced duration for optimal precision [ , ], defined as at least 3 days (LE 2b; GR B), and should be used in patients with predominance of storage symptoms or nocturia (LE 3; GR B; Fig. 6.2 ); for the latter being particularly relevant to categorize the underlying mechanism(s) [ ].
FVC and bladder diaries should be especially used in those men who need objective assessment of urinary frequency and voided volume at baseline or during treatment. These tools are helpful to discriminate between pollakisuria/nocturia due to increased fluid intake, bladder dysfunction, or (nocturnal) polyuria, and they also might be useful in selected patients to document the amount of fluid intake, severity of urgency, and the time of urinary incontinence. By calculating the fraction of urine production during the night (nocturnal polyuria index), nocturnal polyuria is detected (defined as excretion of urine during the night sleeping period ≥ 33% of the total 24 h urine volume). Nocturnal polyuria, which can be detected in up to 80% of men with nocturia, may be caused by increased fluid intake before sleeping, use of diuretics in the evening or night, cardiac insufficiency, obstructive sleep apnoea, or decrease of vasopressin secretion during the night.
Physical Examination and Digital-Rectal Examination
According to the EAU Guidelines on Non-neurogenic Male LUTS [ , ], physical examination focusing on the suprapubic area, external genitalia, perineum, and lower limbs in particular, supplemented by digital-rectal examination (DRE), should be routinely performed in all men (LE 3; GR B; Fig. 6.2 ). Potential pathologies relevant for LUTS (urethral discharge, meatal stenosis, phimosis, penile cancer) can be detected. Trans-anal prostate palpation with the physician’s fingertip is the simplest method to judge the size of prostate, consistency of the prostatic parenchyma for PCa screening, glandular pain for exclusion of prostatitis or a prostate abscess, anal sphincter tone, and the surface of the rectum for exclusion of rectum carcinoma. DRE can sufficiently discriminate prostate volumes smaller or greater than 50 mL [ ], but there is a general underestimation of the prostate size with increasing volume, particularly in prostates with a volume more than 30 mL (tends to be as high as 25% in glands > 50 mL) [ ]. It has to be kept in mind that the chance of PCa in patients with LUTS/BPH is low (approx. 5%–15%) and DRE has a low sensitivity and specificity to detect PCa (around 33% and 50%, respectively).
Urinalysis
Despite the fact that dipstick or microscopic sediment analysis of mid-stream urine is recommended as a primary assessment tool of patients with LUTS [ , ], and must be used according to the EAU Guidelines on Non-neurogenic Male LUTS (LE 3; GR A; Fig. 6.2 ) [ , ], the evidence is limited and concerns exist that costs are outweighed by the benefits of its use [ ]. In case of abnormal findings, the patients should be further evaluated accordingly [ ].
Urinalysis can detect leukocytes, nitrite, erythrocytes/hemoglobin, and glucose. Leukocyte (leukocyte esterase activity) detection is a sign of urinary tract infection, usually caused by bacteria, with Escherichia coli being responsible for most cases [ ], and might be the only cause of LUTS. In cases of leukocytes or positive leukocyte esterase activity detection, a urine sample should be sent for urine culture. All urinary tract infections in elderly men are considered complicated and, therefore, the underlying causes should always be evaluated. Physicians have to keep in mind that urinary tract infections with kidney involvement (pyelonephritis) are the most frequent causes of renal insufficiency. Despite the fact that around 20% of men with LUTS/BPH develop urinary tract infections over time, there is no clear relationship to postvoid residual (PVR) urine. Nitrite in the urine is also a sign of infection since it can be reduced from nitrate by a number of bacteria including E. coli or Proteus , Klebsiella , Pseudomonas , and Staphylococcus species ( Table 6.3 ). The appearance of erythrocytes or hemoglobin in the urine is the result of rupture of superficial prostatic vessels in patients with BPE, but they are also detected in cases with transitional cell carcinoma, urinary stones, urinary tract infections, or glomerulonephritis. Bladder cancer, bladder stones, distal ureter stones, or urinary tract infections might even be the only cause of LUTS. Therefore, all men with hematuria should be further assessed by ultrasound, urethro-cystoscopy, urine cytology, and X-ray investigations to exclude transitional cell carcinoma or stone disease. Most urine dipsticks are also able to detect glucose which, in some men, is the first sign of diabetes mellitus or diabetic bladder dysfunction (initially detrusor overactivity with or without urgency incontinence, later decreased bladder sensation, detrusor underactivity, PVR urine, or even urinary retention).
| Microorganism | Gram Strain | Community (%) | Hospital (%) |
|---|---|---|---|
| E. coli | − | 69.4 | 50.8 |
| Proteus mirabilis | − | 4.3 | 5.1 |
| Klebsiella / Enterobacter species | − | 4.7 | 7.3 |
| Enterococcus species | + | 5.5 | 11.9 |
| Staphylococcus species | + | 4.0 | 8.4 |
| Pseudomonas aeruginosa | − | 0 | 11.1 |
| Others | ± | 12.1 | 5.4 |
Blood Analysis
Serum creatinine is used to judge renal function. However, increased concentration is only seen if ≥ 50% of nephrons are damaged. For better judgment of renal function, calculation of creatinine clearance is recommended (Cockroft-Gault formula):
140 – Age years × body weight kg 72 × serum – creatinine mg / dL
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