Benign prostatic hyperplasia (BPH) is a histological diagnosis; while lower urinary tract symptom (LUTS) is a clinical term that has different causes . In addition, bladder outlet obstruction (BOO) is more a functional and urodynamic definition. As the disease is common and carries cost on the health system, international urology associations provide guidelines to direct urologists into a cost-effective management method [1,2,3▪].
There is no worldwide agreement on how to properly select these patients for treatment or even randomize for clinical trials, neither is about the comprehensive pretreatment evaluation which can reduce the risk of unsatisfactory treatment results.
For a practicing urologist, there has always been dilemma while requesting diagnostic imaging for a BPH patient. This may start with the need for routine imaging, indications for such studies, their accuracy, and predictive value for outcome and complications. None of the questions have received an elucidation so far.
One of the main areas of interest is to find a noninvasive diagnostic method for BOO. During the last 2 years, many authors tried to use new imaging techniques for the diagnosis of LUTS, BPH, and BOO to substitute a cumbersome pressure-flow study. The rationale behind so many novel ideas may be the fact that it is not the prostate size (BPE) that directly correlates with the degree of obstruction. In addition, there may be factors such as urethral dynamic angel, anatomic variations in gland enlargement, prostate capsule elasticity, and vascular component which play a significant role.
In this article, we review the recent findings about the imaging techniques and their use in BPH diagnosis and management.
REVIEW OF LITERATURE
We did a MEDLINE search with these keywords: benign prostatic hyperplasia, bladder outlet obstruction, imaging techniques, BPH diagnosis, BPH management, BPH guidelines, MRI, ultrasound (US), transrectal ultrasound (TRUS). During the study, our focus was on the literature published in the last 2 years.
We reviewed the literature for the problems and tried to figure out results through the controversies. Then, new imaging techniques or improvements are reported.
When should urologists perform imaging in benign prostatic hyperplasia patients?
According to the American Urology Association (AUA) panel in 2005 and its update on 2010, imaging of the upper urinary tract is not recommended as a routine preoperative evaluation. Indications for imaging include infection, hematuria, urolithiasis, and renal insufficiency. Residual urine assessment is an optional test. However, the European Association of Urology (EAU) guideline recommends assessment of the upper urinary tract with either serum creatinine or ultrasonography. Post void residue (PVR) assessment is a routine evaluation during initial assessment [1,2,3▪].
The guidelines offer a cost-effective framework for clinical practice, but they are usually the result of consensus . Therefore, not all of the urologists may follow them.
Bellinger et al.[4▪] reviewed 5% national sample of Medicare beneficiaries from 2000 to 2007 and separated 40 253 new cases to the urology clinic with LUTS and followed them for 12 months. According to their finding, the total expenditure of BPH imaging tests in the USA increased, although this increment was less than the total imaging expenditure increment covered by Medicare at the same range of age. It is also less than the total expenditure increment of other BPH evaluating tests which was also less than overall increment of disease evaluation in the same age range [4▪].
Strope et al.[5,6▪] investigated 10 248 men during their initial visits for BPH by selecting a 5% sample of Medicare patients between the years 1999 and 2007. Patients were excluded if they left the Medicare parts A and B or if they were enrolled in a Medicare HMO for 2 years before the initial visit by the urologist to 1 year after the visit. Patients with prior surgical BPH therapy, prostate cancer or neurologic disease were also excluded.
They studied physician level factor and practice style, the level of recommendation for a test according to AUA guidelines, and the patients’ comorbidities. They noticed that about 15-fold variation among 748 urologists’ average per patient expenditures existed. Costly style in BPH evaluation was detected in the northeast and western part of the USA, among the urologists working in urban area, and who have fewer experiences [5,6▪].
Wei et al. enrolled 6924 men with LUTS and excluded those with lower urinary tract disease or carcinoma, neurological disease, unresolved sexually transmitted disease or urinary tract infection, gross hematuria, acute urinary retention, and previous prostate surgery from January 2004 to February 2005. Urologists performed postvoid residue, prostate ultrasound, and renal ultrasound in 49.5, 24.1, and 13.6% of them, respectively [7,8].
Do they use imaging studies for better differential diagnosis?
The differential diagnoses of LUTS caused by BPH are overactive bladder, detrusor hyperactivity impaired contractility (DHIC), bladder stone, urethral stricture, bladder tumor, underlying medical, neurologic disease, prostate cancer, and problems like congestive heart failure, respiratory or renal disease. More evidence is needed to show that the recommended tests in guidelines are adequate to differentiate BPH from other mentioned diseases.
Is DRE reliable for estimating prostate volume for clinical purpose?
Ahmad et al. concluded that digital rectal examination (DRE) usually underestimates the prostate volume compared to TRUS, but it is an accurate tool for identifying prostates more than 30 cc in 94% of cases. This is adequate for clinical purposes like starting 5ARIs. However, the accuracy is 49.4 and 37.5% in prostates less than 30 cc and more than 80 cc, respectively. In addition, DRE estimation in patients with BMI over 30 is less accurate too .
Could urologists predict their patients’ outcome properly by these recommended assessments before treatment?
According to EAU guidelines, PVR more than 200 cc may indicate bladder dysfunction and predict a less encouraging response . AUA recommends PVR assessment before starting anticholinergics in these patients [3▪].
This could be the reason to measure PVR more than expected in US.
Could they evaluate properly the upper tract damages?
Although 10% of patients with LUTS show some degree of renal insufficiency, it is usually related to concomitant diabetes mellitus (DM) or HTN, and according to Medical Therapy of Prostatic Symptoms (MTOPS) survey the risk of renal insufficiency by LUTS as a single factor is less than 1%. EAU guidelines recommend that as it is hard to say which patient is renal insufficient it is probably cost-effective to measure serum creatinine or performing renal ultrasound. But there is a lack of evidence to evaluate the cost-effectiveness [10,11].
According to AUA guidelines in 2010, renal insufficiency in BPH patients seems to be not more than peers in general population [3▪]. However, again well designed studies are needed to show the cost-effectiveness of this approach. Although assessment of prostate shape and size by transabdominal or transrectal ultrasound is not recommended by EAU guidelines in the first visit, they recommend these evaluations before surgery and medical therapy [10,11]. Therefore, indications for ultrasonography during the disease process should be studied and determined more precisely.
THE NEW IMAGING TECHNIQUES AND CONCEPTS
Most of the recent imaging techniques are experimental and should be evaluated more in well designed clinical trials.
New concepts in transrectal ultrasound
TRUS has been the most common imaging modality for prostate diseases. Recently, new concepts are posed to improve its diagnostic efficacy.
Resistive index measurement by Doppler
Previously, some authors emphasized on the relationship between transitional zone index (transitional zone volume/total prostatic volume) and obstructive symptoms, mechanical bladder outlet obstruction, or acute urinary retention [12,13].
Doppler TRUS provides information about prostate blood flow. Power Doppler can detect low flow small vessels more than color Doppler. The prostate blood supply comes from urethral and capsular arteries. Enlarged transitional zone compresses the surgical capsule, so the vascular resistance in capsular artery will rise. This can be measured by Power Doppler.
Shinbo et al.[13,14], studied a relationship between resistance index = [(peak systolic velocity – end diastolic velocity)/peak systolic velocity], with BOO and risk of acute urinary retention (AUR) in patients with BPH. They studied 1962 men with LUTS and excluded all of the patients with prostatic cancer, prostatitis, urethral stricture, neurogenic bladder dysfunction, renal failure, heart failure, liver cirrhosis, and history of TURP. A total of 245 of them were established AUR. They pointed out that resistance index with cutoff value of more than 0.75 is a more reliable predictor of BOO than international prostate symptom score (IPSS), PVR, and transitional zone index [13,14].
The questions to be answered before using this index in future are the importance and difference between resistance index in capsular or urethral artery, the role of this index in patients who just have medial lobe enlargement, patients who previously received medical therapy, the same age group without symptoms, the effect of heart rate during the study, the effect of patient position during the study, and its reliability in patients with DM, HTN, and vascular disease .
Presumed circle area ratio and capsule elasticity
As prostate enlarges, the pressure transfers to the surgical capsule and finally at one point the capsule cannot stretch more, then prostate begins to transform to a circle shape. The diversity in the elastic characteristic of surgical capsule affects this process and the final outcome will vary in different patients. Presumed circle area ratio (PCAR) is calculated where the horizontal section of prostate in TRUS shows the biggest surface. Then the ratio of this surface to the presumed circle with the same circumference will be calculated. St Sauver et al. designed a cross-sectional study of 328 Caucasian men residing in Olmsted County, Minnesota. They measured IPSS, PVR, peak flow rate, and PCAR. They show that the PCAR greater than 0.9 correlates with symptom score after adjusting for age and prostate volume. But it might not provide predictive information more than transitional zone volume .
Elwagdy et al. started to use 3D extended transrectal ultrasound (3DXI) and then processed images with a software to get multiresolution ones to differentiate the central and transitional zone which is not possible in the routine TRUS. This technique can accurately differentiate the histopathology subtypes of BPH. They used this technique for 113 patients before TURP and compared their results with histopathology of biopsy and TUR specimens. Nodular balance and types (stromal versus glandular) beside the urethra has a correlation with symptom severity and PVR. They supposed that these two factors are more important than surgical capsule elasticity and central gland volume. However, the limited number of patients, lack of control group without the need for surgery, and a long learning curve were the barriers for using it in other centers .
Prostatic urethral angle and intravesical prostatic protrusion
Recent hypothesis about the role of prostatic angle in LUTS  encouraged some authors to examine this theory in LUTS patients. Prostatic urethral angle (PUA) is the angle between prostatic urethra and membranous urethra in midsagittal plane in TRUS. Intraprostatic protrusion (IPP) is the distance between bladder base and the top of protruded prostate into bladder in the same plane.
Park et al. studied 270 LUTS and BPH patients retrospectively, and for minimizing the effect of prostate size on voiding they excluded patients with prostate weight more than 40 cc. Patients with tumor, infection, neurogenic bladder, and stone were also excluded. The IPSS was separated into the storage symptom (IPSS-ss) and voiding symptom (IPSS-vs) subscores. They noticed that IPP was significantly correlated with IPSS, but PUA was correlated just with IPSS-vs and not storage scores. Higher PUA related to higher voiding symptoms .
Ku et al. studied 260 men older than 50 years with IPSS more than 8 and Qmax less than 10 retrospectively. They recorded IPSS, voiding diary, prostate-specific antigen (PSA), PVR, pressure-flow study and uroflowmetry, PUA, and IPP. Patients with higher PUA (PUA ≥35°) had higher PSA, larger prostate volume, higher maximal urethral closure pressure, higher detrusor pressure at maximum flow rate, and higher BOO index. But there was no relationship between the degree of IPP and PUA in that study .
None of these studies measured PUA during voiding, which may change the results. In addition, this index should be compared to an asymptomatic cohort group. Therefore, this parameter needs to be investigated in prospective well designed future studies.
New concepts in abdominal ultrasonography
As mentioned before, there is controversy about the indications of ultrasonography in BPH preoperatively. There have been some innovations to help improve the diagnostic modality.
Intraprostatic protrusion in abdominal ultrasound
IPP is mentioned as a predictive factor of obstruction in several studies. It can be performed either transabdominally or transrectally.
Lee et al., investigated 256 patients with LUTS and BPH by abdominal ultrasound. They measured IPP and categorized them into three subgroups: Grade 1, less than 5 mm; grade 2, 5–10 mm; and grade 3, more than 10 mm. IPSS, uroflowmetry, PVR, and PSA were measured. Progression is defined as PVR more than 100 cc, urinary retention, and worsening of at least 4 points in IPSS score after a mean follow-up of 32 months. The patients received watchful waiting, alfa blocker, or 5ARI. They found a relationship between a higher IPP grade and a higher risk of clinical progression regardless of the treatment types .
Detrusor wall thickness and intraprostatic protrusion
Franco et al. investigated 100 patients older than 50 years with LUTS by abdominal ultrasound and measured IPP and detrusor wall thickness (DWT) when the bladder volume was about 200 cc. All patients with enlarged median lobe, neurological disorders, renal insufficiency, bladder stones, prostate cancer, urethral stricture, previous pelvic surgery, or those who were on treatment were excluded. Patients were assessed with pressure-flow study. They found correlation between these two parameters and BOO index. As a single variable, they found 6 mm cut-off for DWT and 12 mm for IPP. A combination of IPP more than 12 mm and DWT more than 7 mm predicted obstruction better. Patients with one of these two parameters have a 90% chance of BOO on pressure-flow tests and those with none of them have a 66% chance of no obstruction. But more studies with larger case number should be done to find a precise cut-off for these two parameters and also about the standard volume of bladder during the measurement .
Prostate volume measurement by transabdominal ultrasound
Yang et al. after comparing the ultrasound and CT scan measurement of prostate volume in 202 men claimed that the conventional ellipsoid formula is not a valid tool. After analytical analysis, they showed three different prostate shapes during prostate growth. They suggested an eccentricity parameter-based correction to the ellipsoid formula for better estimation. Estimated volume for small prostates by ellipsoid formula differed by 28% from the CT estimated volume. After using the correction, it reached to 7.6%. For large round shape prostate, the difference is less.
Therefore, we need to re-evaluate the conventional ellipsoid formula in high-volume studies if we decide to use transabdominal ultrasound measuring of prostate volume in clinical practice .
Near infrared spectroscopy
Reactive hyperemia occurs in bladder during voiding and it can be detected by near infrared spectroscopy (NIRS). BOO decreases this hemodynamic reaction. NIRS is a method which can monitor these hemodynamic changes by measuring oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) in detrusor muscle using infrared. Chung et al. and Stothers et al. compared NIRS to urodynamic studies in 39 and 64 patients, respectively. Stothers et al. proved a relationship between BOO and NIRS, while Chung et al. could not show any strong relationship. The concept is new and noninvasive and needs to be more investigated in large series with matched control group.
Many studies used MRI to diagnose prostate disease and especially to differentiate BPH from prostate cancer, but none of them could replace prostate biopsy. T2 W1 can distinguish peripheral zone from central zone.
To increase the accuracy of MRI, a number of authors have used special techniques such as dynamic contrast-enhanced (DCE) MRI, magnetic resonance spectroscopy, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) to differentiate cancer from BPH, monitor the medical treatment response, and measure the microvasculature and relaxation properties of prostate. But they are investigational and done in radiology departments with a small number of cases, and a need further investigation [25,26].
New utilization of imaging in benign prostatic hyperplasia treatment
Pisco et al. used angiography to treat BPH. They used arterial embolization with nonspherical 200 μm polyvinyl alcohol particles in 15 BPH patients after failure of response to medical therapy. They could catheterize the selective prostatic artery and embolize at least one pelvic side artery in 14 of them. After a mean follow-up of 7.9 months, IPSS decreased by 6.5 points, prostate volume decreased by 26.5 cc, quality of life improved by 1.14 points, International Index of Erectile Function increased by 1.7 points, and peak urinary flow increased by 3.85 ml/s. They reported one major complication, ischemic area of the bladder wall, and four clinical failures (28.6%). It is obvious that this technique needs to be studied in randomized controlled trials and compared with TURP in future .
Today, evidence-based clinical practice is an essential skill and every urologist should learn how to find the accurate evidence for routine practice.
Indications for diagnostic imaging in BPH remain controversial. All we have are consensuses of expert societies, which still could be reliable as a cost-effective framework for clinical practice.
Many novel noninvasive imaging techniques are arising, but most are in the experimental phase. Among them, IPP via TRUS or abdominal ultrasonography and eccentricity parameter-based correction of prostate volume calculation through abdominal ultrasound seem more promising. However, none could replace the valuable pressure-flow study yet.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 96).
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