Approach Considerations
Most cases of chronic bacterial prostatitis (CBP) can be diagnosed with history, physical examination, and urine or semen culture. A urine dipstick is often done as the same time as urine culture collection to evaluate for signs of infection and hematuria.
The formal diagnosis of CBP includes a history of recurrent urinary tract infections (UTIs) and a 10-fold increase in bacteria in expressed prostatic secretion (EPS), post-massage urine, or semen culture. [31] As discussed below, the "four-glass test" to collect EPS is the gold standard for diagnosis, but this test is cumbersome and not widely used in the clinical setting; often a urine or semen culture is adequate for diagnosis.
If urine or semen cultures are not diagnostic and the patient has symptoms suggestive of CPPS, additional tools are recommended for evaluation, including the following:
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UTI localization test (two-glass)
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Urinary flow rate
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Postvoid residual determination
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Urine cytology
To exclude other diagnoses on the differential such as infections, stones, abscesses, obstruction, or prostate cancer, further tests can be done, including the following:
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Urethral swab and culture
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Screening for sexually transmitted infections
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Prostate-specific antigen (PSA) testing
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Uroflowmetry
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Retrograde urethrography
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Cystoscopy
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Prostate biopsy
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Transrectal ultrasound
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Renal ultrasound
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Prostate biopsy
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Magnetic resonance imaging (MRI) or computed tomography (CT) scan
Prostatic Massage
The prostatic massage is needed to collect an expressed prostatic specimen (EPS) or post-massage urine to help localize the bacterial infection. It is done during the rectal examination by kneading the prostate from front to back and from lateral to medial until a milky fluid is obtained from the urethra. This may require as long as a minute of fairly vigorous massage and the patient should be informed of this. Please refer to Diagnostic Prostatic Massage / Technique/Approach Considerations for more details on performing prostatic massage.
Urinary Tract Localization Tests
Collecting urine specimens before, during, and after prostatic massage can help localize the bacterial infection within the urinary tract. The traditional four-glass urine collection technique, as described by Meares and Stamey in 1968, includes examination of four urine specimens. The collection procedure is as follows:
- The first specimen is voided bladder–1 (VB1), which is the first 10 mL of urine and represents the urethral specimen.
- The patient then voids another 100-150 mL of urine.
- The second specimen, voided bladder–2 (VB2), is collected, which is another 10 mL of urine and represents the bladder specimen.
- The third specimen is the expressed prostatic specimen (EPS), which is the fluid collected during prostatic massage.
- The fourth specimen, voided bladder–3 (VB3), consists of the first 10 mL of urine collected after EPS; it contains any EPS trapped in the prostatic urethra.
All four specimens are sent for culture. [5] The three urine specimens are centrifuged and the sediment is examined with microscopy to identify signs of inflammation, including white blood cells/aggregates, macrophages, oval fat bodies, bacteria and fungal hypha. A wet mount can be used to examine the EPS with microscopy, as well.
The two-glass test, also known as pre-massage and post-massage test, is simple and cost-effective. It is used more commonly in clinical practice to screen patient with prostatitis. The pre-massage urine specimen is midstream catch and the post-massage urine specimen is the initial 10 mL after prostatic massage. The sediment is evaluated with microscopy and the urine is cultured. See the image below.
Urine culture with greater than 100,000 colony-forming units (CFU) of Escherichia coli, the most common pathogen in acute and chronic prostatitis. Chronic bacterial prostatitis must be confirmed and diagnosed using a urine culture.
If infection is present but localization of the infection is not possible, which suggests acute cystitis, the patient can be treated with nitrofurantoin or another antibiotic that does not penetrate the prostate well, to clear the infection from the urine, and the procedure can then be repeated. If bacteria are subsequently localized to the EPS or VB3, then CBP can be diagnosed.
CBP is also associated with prostatic inflammation, which is 10 or more white blood cells per high-power field (WBCs/HPF). This is not a specific finding; it is commonly associated with nonbacterial prostatitis, asymptomatic inflammatory prostatitis, urethritis, prostatic stones, or recent ejaculation and therefore does not add significant clinical information to aid in diagnosis.
Semen culture
Semen cultures are a simpler test than the gold standard four-glass test. The sensitivity of semen cultures for diagnosing CBP has been reported between 10%-100%. [32] The significance and diagnostic value of semen culture remains controversial and further studies are needed to determine whether semen culture alone may represent a reasonable diagnostic alternative.
Budia et al retrospectively studied 895 patients with chronic prostatitis/CPPS who all had EPS and/or VB3 specimens as well as semen cultures done. They reported that semen cultures had higher sensitivity than EPS samples for gram-negative organisms (97% versus 82.4%) and for gram-positive cultures (100% versus 16.1%). [33]
Magri et al conducted a retrospective study of 696 patients with prostatitis symptoms who had a four-glass test and semen culture analyzed for bacteriological work-up. They found that semen cultures are a useful adjunctive diagnostic tool and there were no differences in eradication rates (using combination treatment with a fluoroquinolone and a macrolide) between patients diagnosed with different tests. [34]
Zegarra Montes et al conducted a prospective comparison of diagnosis with a semen culture versus diagnosis with the four-glass test, in 70 men with symptoms consistent with chronic prostatitis along with 17 asymptomatic controls. Semen culture had a sensitivity of 45% and specificity of 94%.These authors concluded that a positive semen culture in a symptomatic patient may be sufficient to justify starting treatment with antibiotics but a negative culture does not rule out CBP. [32]
Prostate-Specific Antigen Testing
Routine PSA testing during a prostatitis episode is not recommended. Most patients with clinically proven bacterial prostatitis have an elevated PSA value independent of any cancer-related elevation. No prostatitis-adjusted tables are available to indicate which PSA values are inappropriate in this patient population.
In patients with bacterial prostatitis who have an elevated PSA value, a reevaluation of the PSA value 6-8 weeks after appropriate treatment is recommended to ensure the value is decreasing to normal levels. It is also appropriate to review the patient’s recent PSA values as a point of comparison. If values remain elevated after appropriate therapy, prostate biopsy is recommended to rule out concomitant pathology.
PSA testing should be considered to exclude prostate cancer only if the findings on digital rectal examination (DRE) raise concern. If PSA testing is done, it should be postponed as follows:
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After DRE - 1 week
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After treatment for a UTI - 6 weeks
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After prostate biopsy - 6 weeks
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After vigorous exercise or sexual intercourse - 48 hours
Imaging Studies
Retrograde urethrography
Retrograde urethrography is performed to help confirm the presence of a urethral stricture and evaluate its severity. It is performed by injecting contrast into the urethral meatus and obtaining pelvic radiography. If a stricture is present, narrowing of urethral caliber is observed.
Transrectal ultrasound
Transrectal ultrasonography of the prostate cannot be used to formally diagnose CBP. Although hypoechoic lesions representing calcifications within prostate may suggest the infection and inflammation associated with CBP, these findings are highly nonspecific. Transrectal ultrasonography findings may also help to identify prostatic stones. In certain patients with frequent recurrences, these stones may be a contributing factor in CBP.
Transrectal ultrasound is useful only if a prostatic abscess exists. Abscesses are extremely rare, but if they are present, patients may also have a high fever and appear quite ill. CT scanning may also be helpful in this situation if transrectal ultrasonography is not available. MRI may also be used but is not as readily available in most acute situations.
Other Tests
Uroflowmetry
Uroflowmetry is a simple urodynamic test to help evaluate the rate of urine flow over time. It is used in patients with prostatitis to help evaluate for obstruction secondary to a urethral stricture or prostatic enlargement. Results are obtained in graphic form. Normal results show a rapid rise to a peak and then a gradual drop-off back to baseline.
A urethral stricture is indicated by a rapid rise to a low point, a plateau for the remainder of the study, and then a drop-off at the termination of the study. In prostatic enlargement, a wide variety of patterns may be present, but the peak flow is usually less than 15 mL/s, and a stop-start pattern may also be present. To help delineate abnormalities and to differentiate a stricture from prostatic enlargement, cystoscopy should be performed.
Postvoid residual testing
Postvoid residual testing measures the volume of urine left in the bladder immediately after voiding. This volume can be measured by catheterizing the bladder or by using a bladder scanner. Although the results are nonspecific, they can give clues to the presence of lower tract dysfunction, which may require surgical intervention to relieve prostatic obstruction or urethral stricture.
Urodynamics
If patients have not responded to standard therapy or they have abnormalities on uroflometry or postvoid residual tests, further urodynamic studies may provide more information or diagnose a chronic voiding dysfunction. Video-urodynamics can be used to evaluate patient with storage or voiding symptoms to look for urethral obstruction, abnormalities of vesical neck, external sphincter dyssynegia, detrusor overactivity, or acontractile bladder. In patients with classic CBP symptoms, urodynamic studies may not provide any useful diagnostic information.
Procedures
Prostate Biopsy
This is the most definitive, but least practical, modality used to diagnose bacterial prostatitis. The biopsy sample can serve as a specimen for culture, which if positive provides a definitive diagnosis. Viewing the sample under microscopy can help to identify a focal infiltration of inflammatory cells into the prostatic stroma. Again, the finding of inflammation is not specific to CBP. Category IV prostatitis is sometimes diagnosed using prostate biopsy. Category IV prostatitis is asymptomatic but may be responsible for elevations in PSA levels, resulting in the need for a diagnostic biopsy to help exclude prostate cancer.
However, prostate biopsy carries a risk of complications, including bleeding, injury to surrounding structures, and infection. In the face of an active infection such as acute prostatitis, performing a biopsy could precipitate sepsis. Overall, prostate biopsy is not recommended as a diagnostic modality for CBP and should be done only if prostate cancer is suspected on the basis of PSA level and/or DRE findings.
Endoscopy (Cystoscopy)
Lower urinary tract endoscopy (cystoscopy) is only indicated for patients with concern for lower urinary tract malignancy (hematuria), stones, urethral strictures, bladder neck abnormalities or other surgically corrected abnormalities. It may be justified in patients in whom standard therapy has failed, but clinical experience suggests that it is not indicated for most men with chronic prostatitis. [1]
Histologic Findings
Prostatitis, from a pathologist standpoint, is an increased number of inflammatory cells within the prostatic parenchyma. As with inflammatory markers in urine, inflammation of the prostate is not specific to prostatitis and can be found in patients without prostate disease. Therefore, biopsy is rarely used to diagnose prostatitis. Biopsies done to evaluate for prostate cancer commonly show chronic inflammation and if patients area asymptomatic they are categorized as IV prostatitis (asymptomatic inflammatory prostatitis) (See the image below.)
A nonspecific, mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.
Inflammation of the prostate tends most commonly follows a pattern of stromal lymphocytic infiltrates adjacent to acini, but varies and may also include glandular or periglandular inflammation in patient with chronic prostatitis. [1]
Prostatic calculi may also be associated with inflammation as they obstruct prostatic ducts limiting drainage or provide a nidus for bacteria, which can contribute to inflammation.
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Bacterial prostatitis. Expressed prostatic fluid contains more than 10 white blood cells per high-power field, indicating prostatitis.
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US National Institutes of Health chronic prostatitis symptom index.
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A nonspecific, mixed inflammatory infiltrate that consists of lymphocytes, plasma cells, and histiocytes is typical in chronic bacterial prostatitis.
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Urine culture with greater than 100,000 colony-forming units (CFU) of Escherichia coli, the most common pathogen in acute and chronic prostatitis. Chronic bacterial prostatitis must be confirmed and diagnosed using a urine culture.
