Amin S. Herati, MD
Robert M. Moldwin, MD, FACS
BASICS
DESCRIPTION
• Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), NIH categories IIIA and IIIB are characterized by pelvic, perineal, and/or testicular pain ± LUTS in the absence of other well-defined pathology.
– IIIA: Inflammatory CPPS: WBCs present in prostatic secretions
– IIIB: Noninflammatory CPPS: WBCs not present in prostatic secretions
EPIDEMIOLOGY
Incidence
N/A
Prevalence
Estimated prevalence of CP/CPPS is 1.8%, equating to approximately 2,000,000 US men (1).
RISK FACTORS
• Urethral catheterization or instrumentation
• Inadequately treated urinary tract infections
• Pelvic trauma
• Urethral strictures
• Psychological stress or depression
Genetics
• A large proportion of patients with CP/CPPS express the IL-10 AA genotype with low IL-10 expression
• Category IIIA patients are more likely to have a low TNFα genotype
PATHOPHYSIOLOGY
• 90% of cases of CP/CPPS have an unclear etiology, the remainder of cases can be attributed to bacterial in origin (Category II)
• Although the exact cause is not known, it is thought to be multifactorial with a combination of factors contributing to the pathophysiology (image)
• Current theories include:
– Nanobacterial colonization
– Atypical bacterial infection
– Voiding dysfunction causing intraprostatic urinary reflux and elevated intraprostatic pressure
– Pelvic floor muscle dysfunction
– Endocrine
– Neuropathic
– Autoimmune
• Stratification of each patient into a 6-point clinical phenotyping system, termed UPOINT, based on likely etiologic mechanisms has been proposed to improve outcomes by tailoring therapies to target the involved mechanisms (2).
ASSOCIATED CONDITIONS
• Allergies
• Sinusitis
• Erectile dysfunction
• Irritable bowel syndrome
• Depression
• Fibromyalgia
• Fatigue
• Neurologic disorders
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Determine duration of symptoms (of at least >3-mo duration)
• Pain in the suprapubic region, lower back, penis, testes, and/or scrotum
• Painful ejaculation: One of the most discriminatory symptoms associated with CP/CPPS III and a strong predictor of QOL and severity of pain (3)
• Sexual dysfunction
• Pelvic floor muscle spasms
• Irritative and obstructive voiding symptoms
– Urgency
– Frequency
– Hesitancy
– Poor interrupted flow
• History should also cover neurologic disease, hematologic, cardiovascular, and infectious diseases
• NIH-CPSI is a validated questionnaire assessing pain, urinary function, and QOL. Can be used to measure symptoms upon initial presentation and follow-up
PHYSICAL EXAM
• Careful exam of the genitalia, groin, perineum, coccyx, external anal sphincter, and internal pelvic floor and side walls
• Exam is usually unremarkable except for pain: Degree of pain not helpful in differentiating between various categories of CP/CPPS
• Digital rectal exam should not be performed until urine from preprostatic massage has been collected
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis and urine culture
• Stamey test (Meares–Stamey 4-glass test)—considered to be “gold standard” in diagnosis
• Limitations: EPS cannot be obtained in all patients, variable interpretation of WBC counts, difficult-to-culture organisms not routinely identified
• 2-glass test (premassage and postmassage test)
– Difficulties encountered with interpretation of bacterial localization studies as asymptomatic individuals often harbor uropathogens
Imaging
• Pelvic imaging with ultrasonography, CT, or MRI is considered optional and can be obtained if clinically indicated to rule out other causes of pelvic pain
• TRUS has poor specificity in differentiating among the subtypes of CP/CPPS
Diagnostic Procedures/Surgery
• Stamey test (Meares–Stamey 4-glass test)
• Video-urodynamics: Should be considered in patients with significant lower urinary tract symptoms in addition to pain. Findings often include decreased peak and mean urinary flow rates, elevated maximal urethral closing pressure, incomplete funneling of the bladder neck, and urethral narrowing at the level of the external urethral sphincter (4)
• Cystoscopy is not indicated in the majority of cases: Can be performed if history indicates other etiology
• Prostate biopsy: Tissue for culture not helpful in diagnosis and not recommended
Pathologic Findings
Not formally reported for Category III, therefore N/A
DIFFERENTIAL DIAGNOSIS
• Acute or chronic bacterial prostatitis
• Benign prostatic hyperplasia
• Bladder calculus
• Bladder cancer
• Bladder neck contracture
• Interstitial cystitis
• Primary voiding dysfunction
• Prostate abscess
• Prostate cancer
• Prostate cyst
• Radiation cystitis
• Tuberculosis of the prostate
• Urethral stricture
• Urethritis
TREATMENT
GENERAL MEASURES
• As the pathogenesis of CP/CPPS category III is considered multifactorial, effective treatment for CP/CPPS III often requires multimodal therapy
• A meta-analysis comparing α-Blockers, antibiotics and anti-inflammatory/immune modulating therapies found a combination of α-blockers and antibiotics to be superior to α-blockers, antibiotics, or anti-inflammatory/immune modulating therapies alone in the reduction of NIH-CPSI scores (5)
• Treatment should also be targeted to the etiologic mechanisms using the UPOINT system
• Focus of therapy should be on symptom relief
• Conservative measures such as diet modification, myofascial physical therapy, phytotherapies, acupuncture should be considered as part of the 1st-line therapy
• Symptoms should be followed with NIH-CPSI questionnaires and voiding diaries
MEDICATION
First Line
• The choice of agents in the 1st- or 2nd-line setting is practitioner dependent with no specific agent approved specifically for this condition
• α-Blockers: Multiple randomized, placebo-controlled trials have demonstrated a duration of at least 3 mo or longer may be needed before assessment can be made of treatment failure or success.
– Side effects of α-blockers include hypotension, dizziness, fatigue, and retrograde ejaculation
Alfuzosin 10 mg BID for 12 wk; contraindicated with moderate hepatic insufficiency or with cytochrome P450 3A4 inhibitors
Doxazosin 1–4 mg daily for 12 wk; escalate dose until symptom relief obtained
Tamsulosin 0.4 mg daily for 12 wk
Terazosin 1–5 mg daily; escalate dose until symptom relief obtained
Silodosin (8 mg/d)
• Antibiotic therapy: Data conflicting on the benefit and therapeutic benefit should be reassessed after 2 to 4 wk of initiating therapy
– Can be considered in antibiotic-naïve patients
– Fluoroquinolones: Side effects include dizziness, restlessness, headache, nausea, rash
Ciprofloxacin, levofloxacin 500 mg daily for 4 wk (some concern over growing resistance to this class of drugs)
Trimethoprim–sulfamethoxazole 160/80 mg BID for 4 wk: Side effects include anorexia, nausea, vomiting, rash, urticaria
• 5α-Reductase inhibitor:
– Finasteride 5 mg daily or
– Dutasteride 0.5 mg daily
• Anti-inflammatory agents
– Rofecoxib 25–50 mg daily: Symptom relief at higher doses, but not recommended because of cardiovascular risk
– Oral prednisolone
• Pentosan polysulfate 100 mg TID
• Gabapentanoids
– Pregabalin 150–600 mg daily
• Muscle relaxants
– Baclofen
– Diazepam
Second Line
See above
SURGERY/OTHER PROCEDURES
• Not recommended. Last resort unless other indications are discovered during the workup
– Transurethral microwave thermotherapy
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
See below
Complementary & Alternative Therapies
• Dietary and lifestyle modification
• Phytotherapy
– Pollen extract
– Quercetin
– Saw palmetto
• Acupuncture
• Myofascial physical therapy
• Stress management/cognitive-behavioral therapy
• Frequent ejaculation
ONGOING CARE
PROGNOSIS
Remissions and flare-ups common over the long term
COMPLICATIONS
None known
FOLLOW-UP
Patient Monitoring
Long-term supportive care
Patient Resources
• Urology Care. Foundation. http://www.urologyhealth.org/urology/index.cfm?article=15
• http://www.prostatitis.org
REFERENCES
1. Suskind AM, Berry SH, Ewing BA, et al. The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: Results of the RAND Interstitial Cystitis Epidemiology Male Study. J Urol. 2013;189:141–145.
2. Shoskes DA, Nickel JC, Kattan MW. Phenotypically directed multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome: A prospective study using UPOINT. Urology. 2010;75:1249–1253.
3. Shoskes DA, Landis JR, Wang Y, et al; Chronic Prostatitis Collaborative Research Network Study Group. Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome (CPPS). J Urol.2004;172:542–547.
4. Barbalias GA, Meares EM Jr, Sant GR. Prostatodynia: Clinical and urodynamic characteristics. J Urol. 1983;130:514–517.
5. Thakkinstian A, Attia J, Anothaisintawee T, et al. α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome. BJU Int.2012;110:1014–1022.
ADDITIONAL READING
• Nickel JC. Prostatitis and related conditions, orchitis, and epididymitis. In: Wein AJ, Kavoussi LR, Novick AC, et al. eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Elsevier; 2011.
• Schaeffer AJ. Chronic Prostatitis and the chronic pelvic pain syndrome. N Eng J Med. 2005;355:1690–1698.
See Also (Topic, Algorithm, Media)
• NIH-CPSI Questionnaires
• Prostatitis, Acute Bacterial (NIH I)
• Prostatitis, Asymptomatic Inflammatory (NIH IV)
• Prostatitis, Chronic Bacterial (NIH II)
• Prostatitis, Chronic Nonbacterial, Inflammatory and Noninflammatory (NIH CP/CPPS III A and B) Image 
• Prostatitis, General
• Stamey Test (3-glass test, 4-glass tests, Meares–Stamey Test)
CODES
ICD9
• 338.4 Chronic pain syndrome
• 601.1 Chronic prostatitis
• 789.09 Abdominal pain, other specified site
ICD10
• G89.29 Other chronic pain
• N41.1 Chronic prostatitis
• R10.2 Pelvic and perineal pain
CLINICAL/SURGICAL PEARLS
Multimodal therapy is oftentimes required because of the varied pathologies associated with this condition.