Mr. R.J. is a 38-year-old man who presents with a 5-month history of increasing pelvic pain. He describes an intense stabbing pain in the perineum that radiates to the testicles and the tip of the penis. The pain was initially sporadic (initially 3-4 times per week), but while it still waxes and wanes, it’s now becoming more persistent and even debilitating. The patient also reports some increasing urinary frequency and urgency. He recounts a history of good erectile function, but with pain during and after ejaculation. This has led to decreasing interest in sex, which is now affecting his relationship with his wife. He’s otherwise healthy, and takes no medications. His physical exam reveals a soft, non-tender abdomen, with normal external genitalia. A digital rectal exam provokes acute pain, and reveals a soft, small prostate. Screening neurological exam is non-contributory.
Presumptive diagnosis: chronic prostatitis
Prostatitis is the most common urologic diagnosis in men younger than 50 years and the third most common in men older than 50 years, after BPH and prostate cancer.
Classification of prostatitis syndromes
Prostatitis syndromes are classified by the National Institute of Health (NIH) according to presumed etiology and clinical findings. These include culture and microscopic findings from expressed prostatic secretions, pre- and post-prostatic massage urine sediment or semen analysis.
Category I or acute bacterial prostatitis (ABP) is an acute infection of the prostate and is manifested by systemic signs of infection, and a positive urine culture.
Category II or chronic bacterial prostatitis (CBP) is a chronic bacterial infection where bacteria are recovered in significant numbers from a purulent prostatic fluid. This is believed to be the most common cause of recurrent urinary tract infection in men.
Category III or chronic pelvic pain syndrome (CPPS) is diagnosed when no pathogenic bacteria can be localized to the prostate (culture of expressed prostatic fluid and/or post-prostatic massage urine specimen) and is further divided into IIIa and IIIb. Category IIIa refers to inflammatory CPPS where a significant number of WBCs are localized to the prostate; while category IIIb is non-inflammatory.
Category IV refers to asymptomatic inflammatory prostatitis where bacteria or WBCs are localized to the prostate, but the patient is asymptomatic. This is not an important category for primary care physicians.
Etiology of prostatitis syndromes
ABP and CBP (Categories I and II) are mostly caused by gram-negative Enterobacteriaceae and Enteroccocci species that originate in the gastrointestinal flora. The most common organism is Escherichia coli, which is identified in the majority of infections. Pseudomonas aeruginosa, Serratia species, Klebsiella species, and Enterobacter aerogenes account for most of the rest of the cultured organisms. Nonbacterial prostatitis (CPPS) syndromes are caused by a cascade of inflammatory, immunologic, neuroendocrine and neuropathic mechanisms, which begin with an initiator (perhaps an initial infection) in a genetically or anatomically susceptible man.
Evaluation of acute prostatitis
Patients suspected of having ABP (Category I) present with symptoms of a severe lower urinary tract infection with variable obstructive voiding symptoms and very commonly systemic symptoms of fever, nausea and vomiting. Evaluation consists of a complete physical examination including digital rectal exam (very tender prostate), urinalysis (evidence of infection) and a urine culture to confirm the diagnosis.
Evaluation of chronic prostatitis and chronic pelvic pain syndrome
Chronic bacterial prostatitis is suggested by a history of recurrent urinary tract infection. Patients are often asymptomatic between these episodes but as they become more frequent, symptoms tend to persist. The Chronic Prostatitis Symptom Index (CPSI) is a useful clinical questionnaire, since objective parameters in this disease are often lacking. The CPSI consists of 9 questions evaluating 3 key domains: pain, urinary function, and quality of life. Pain, which is usually the most important feature of CP/CPPS, is captured in 4 questions assessing location, severity, and frequency. Urinary function is evaluated with 2 questions assessing obstructive and irritative symptoms. Quality of life is evaluated with 3 questions looking at the impact of symptoms on activities of daily living.
Beyond symptom assessment, a physical exam is an important part of the evaluation, although it’s usually unhelpful in diagnosing CPPS or further classifying it. To further classify chronic prostatitis, analysis and culture of urine before and after a prostatic massage is necessary. A simple 2-glass technique has been shown to be a highly effective and practical evaluation method to rule out infection (Category II CBP). It consists of a mid-stream urine followed by collection of the first 10 cc of urine following a vigorous prostate massage. Significant bacteriuria in the post-prostatic massage urine specimen or an increased bacterial count compared to the pre-prostatic massage specimen indicates localization of infection in the prostate (Category II). Most patients will have negative or non-localizing cultures (Category III CPPS). Primary care physicians shouldn’t bother doing microscopy on the spun-down sediment of these specimens — even the experts are unsure of how to use that information.
Antimicrobials are the most commonly prescribed agents for all categories of prostatitis. Their use for acute and chronic bacterial prostatitis is based on objective culture results, but they also remain the first-line treatment for other categories of prostatitis, based on a belief that most CP syndromes may be at least initially caused by bacteria.
Trimethoprim-sulfamethoxazole (TMP-SMX) or trimethoprim alone were widely used in previous decades for both acute and chronic prostatitis. Bacterial eradication was reported to be poor in most studies, with a long duration of treatment required (90 days). The fluoroquinolones have demonstrated better results. Norfloxacin, ciprofloxacin, ofloxacin, and levofloxacin offer a much higher bacterial eradication rate with shorter duration of treatment in category II chronic bacterial prostatitis. In Category I ABP, patients may have to be started on parenteral antibiotics and switched to oral therapy (2-4 weeks) once they have improved. The minimum duration of therapy for Category II CBP is 4 weeks.
Strong evidence exists that ciprofloxacin and levofloxacin are ineffective in Category III CPPS patients who have been symptomatic for many years and have been heavily treated previously. But there’s moderate evidence that empiric use of antibiotics during initial presentation in antibiotic naïve patients results in significant amelioration of symptoms.
The clinical evidence on the effects of alpha-blockers such as terazosin, tamsulosin, and alfuzosin on Category III CPPS has been conflicting. They appear to be useful only in patients with recent disease onset and with voiding symptoms, who haven’t been heavily treated. Treatment must be continued for at least 6 weeks.
Other medical therapies
Anti-inflammatories such as COX-2 inhibitors have shown modest benefit in CPPS patients. The 5-alpha reductase inhibitors, finasteride and dutasteride, may be helpful in older patients with concurrent benign prostatic hyperplasia (for more on BPH, see page 46). A number of phytotherapeutic agents such as pollen extract and quercetin provide modest benefit. Neuromodulatory intervention (for example, tricyclic antidepressants and gabapentinoids) show promise for refractory patients who develop a chronic pelvic neuropathic type of pain. Muscle relaxants provide some relief for patients with skeletal muscle pain and spasm.
Short-term Foley catheterization is helpful in patients with Category I ABP who have difficulty voiding. Occasionally, these patients develop a prostate abscess, and surgery is indicated for drainage. Surgery for the chronic bacterial prostatitis syndromes should be reserved only for those with definite indications (such as urethral stricture or bladder neck obstruction). Transurethral resection of the prostate gland is not recommended and while radical prostatectomy may prevent the recurrent urinary tract infections associated with Category II CBP, it’s really a drastic step. Microwave thermotherapy of the prostate has shown some promise in CPPS, but the evidence is not strong.
Emerging concept of heterogenous clinical phenotypes in chronic prostatitis syndromes
There’s no single treatment that fits all chronic prostatitis patients in real clinical practice. It’s becoming increasingly clear that CBP and CPPS patients aren’t a homogenous group with common etiology and symptoms, but rather a heterogeneous group with widely differing clinical “phenotypes.” So it’s unlikely that we’ll ever find a panacea for this challenging clinical entity. Rather, the need is to identify which subgroup of patients will respond to a particular therapy.
A clinically practical phenotyping classification system for patients diagnosed with urologic chronic pelvic pain syndromes (UCPPS) has recently been proposed. UPOINT is a 6-point clinical classification system that categorizes the phenotype of patients with UCPPS into one or more of 6 clinically identifiable domains: Urinary, Psychosocial, Organ Specific, Infection, Neurologic/Systemic and Tenderness (muscle). A physician can quickly categorize each patient into one or more of these UPOINT domains and then develop an individual therapeutic plan specifically addressing the clinical phenotypes identified (most patients will be categorized with more than one UPOINT domain and will require multimodal therapy).
Naji Touma, MD, is on the faculty of the department of urology at Queen’s University, Kingston, ON.
J. Curtis Nickel, MD, is a professor in the department of urology at Queen’s University, Kingston, ON, and heads the Prostatitis Clinical Research Centre.
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