Abstract
Introduction
Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic abacterial prostatitis/chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, biofeedback, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs, oral antimicrobial drugs, pentosan polysulfate, prostatic massage, quercetin, radical prostatectomy, sitz baths, transurethral microwave thermotherapy, and transurethral resection.
Key Points
Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS).
Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.
Chronic bacterial prostatitis has identifiable virulent micro-organisms in prostatic secretions.
Oral antimicrobial drugs are likely to be beneficial, although studies comparing them with placebo or no treatment have not been found.
Clinical success rates from oral antimicrobials have reached about 70-90% at 6 months in studies comparing different regimens.
Trimethoprim-sulfamethoxazole (co-trimoxazole) and quinolones are most commonly used and seem the most beneficial.
Alpha-blockers may reduce symptoms and reduce recurrence of chronic prostatitis if added to antimicrobial treatment.
We don't know whether local injections of antimicrobial drugs, NSAIDs, transurethral resection, or radical prostatectomy improve symptoms compared with no treatment.
Effective treatment regimens for CP/CPPS remain to be defined, and strategies are based on symptomatic control and anxiety relief.
Alpha-blockers may improve quality of life and symptoms compared with no treatment.
Oral antimicrobial drugs have not been shown to improve symptoms.
We don't know whether 5 alpha-reductase inhibitors, NSAIDs, pentosan polysulfate, allopurinol, transurethral microwave thermotherapy, prostatic massage, Sitz baths, biofeedback, mepartricin, or quercetin reduce symptoms in men with CP/CPPS.
About this condition
Definition
Chronic bacterial prostatitis is characterised by a positive culture of expressed prostatic secretions. It may cause symptoms such as suprapubic, lower back, or perineal pain, with or without mild urgency and increased frequency of urination, and dysuria, and may be associated with recurrent UTI. However, it may also be asymptomatic between acute episodes/exacerbations. Chronic abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS), is characterised by pelvic or perineal pain in the absence of pathogenic bacteria in expressed prostatic secretions. It is often associated with irritative and obstructive voiding symptoms including urgency, frequency, hesitancy, and poor interrupted flow. Symptoms can also include: pain in the suprapubic region, lower back, penis, testes, or scrotum; and painful ejaculation. CP/CPPS may be inflammatory (white cells present in prostatic secretions) or non-inflammatory (white cells absent in prostatic secretions). A classification system for the prostatitis syndromes has been developed by the National Institutes of Health (NIH).
Incidence/ Prevalence
One community-based study in the USA (cohort of 2115 men aged 40-79 years) estimated that 9% of men have a diagnosis of prostatitis at any one time. Another observational study found that, in men presenting with genito-urinary symptoms, 8% of those presenting to urologists and 1% of those presenting to primary-care physicians were diagnosed as having chronic prostatitis. Most cases of chronic prostatitis are abacterial. Chronic bacterial prostatitis, although easy to diagnose, is rare.
Aetiology/ Risk factors
Organisms commonly implicated in bacterial prostatitis include Escherichia coli, other Gram-negative enterobacteriaceae, occasionally Pseudomonas species and, rarely, Gram-positive enterococci. Risk factors for bacterial prostatitis include urethral catheterisation or instrumentation, condom drainage, dysfunctional voiding (high-pressure urination), and unprotected anal intercourse. The cause of CP/CPPS is unclear, although it has been suggested that it may be caused by undocumented infections with Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis. Viruses, Candida (in immunosuppressed people), and parasites have also rarely been implicated. Non-infectious factors might also be involved, including inflammation, autoimmunity, hormonal imbalances, pelvic floor tension myalgia, intraprostatic urinary reflux, and psychological disturbances. In one case control study (463 men with CP/CPPS, 121 asymptomatic age-matched controls), when compared with controls, men with CP/CPPS reported a significantly higher lifetime prevalence of non-specific urethritis (12% with CP/CPPS v 4% with no CP/CPPS; P = 0.008), CVD (11% with CP/CPPS v 2% with no CP/CPPS; P = 0.004), neurological disease (41% with CP/CPPS v 14% with no CP/CPPS; P less than 0.001), psychiatric conditions (29% with CP/CPPS v 11% with no CP/CPPS; P less than 0.001), and haematopoietic, lymphatic, or infectious disease (41% with CP/CPPS v 20% with no CP/CPPS; P less than 0.001). Further studies are necessary to determine whether these factors play a role in the pathogenesis of CP/CPPS.
Prognosis
The natural history of untreated chronic bacterial and abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains ill-defined. Chronic bacterial prostatitis may cause recurrent UTI in men whereas CP/CPPS does not. Several investigators have reported an association between chronic bacterial prostatitis, CP/CPPS, and infertility. One study found that CP/CPPS had an impact on quality of life similar to that of angina, Crohn's disease, or a previous MI.
Aims of intervention
To relieve symptoms and eliminate infection where present, with minimum adverse effects.
Outcomes
Symptom improvement (symptom scores, bother scores); quality of life; urodynamics; rates of bacteriological cure (clearance of previously documented organisms from prostatic secretions); adverse effects of treatment.
Methods
BMJ Clinical Evidence search August 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to August 2007, Embase 1980 to August 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 3. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language. RCTs had to be at least single-blinded where possible to blind, and contain 20 or more individuals, of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
Important outcomes | Symptom improvement, cure rates, recurrence rates, quality of life, adverse effects | ||||||||
Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
What are the effects of treatments for chronic bacterial prostatitis? | |||||||||
2 (443) | Symptom improvement | Oral antimicrobial drugs v each other | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for narrow range of comparators |
3 (532) | Cure rates | Oral antimicrobial drugs v each other | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for narrow range of comparators |
1 (64) | Recurrence rates | Alpha-blockers plus antimicrobial drugs v antimicrobial drugs alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
1 (50) | Symptom improvement | Locally injected antimicrobial drugs v each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for restricted population |
1 (50) | Cure rates | Locally injected antimicrobial drugs v each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for restricted population |
What are the effects of treatments for chronic abacterial prostatitis/chronic pelvic pain syndrome? | |||||||||
7 (at least 294) . | Symptom improvement | Alpha-blockers v placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results and flaws with randomisation. Consistency point deducted for different results for different outcomes |
1 (86) | Quality of life | Alpha-blockers v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
2 (105) | Symptom improvement | 5 alpha-reductase inhibitors v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for sparse data and incomplete reporting of results |
1 (54) | Symptom improvement | Allopurinol v placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, poor follow-up, and incomplete definition of reported outcome |
1 (26) | Symptom improvement | Mepartricin v placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for different results for different outcomes |
1 (26) | Quality of life | Mepartricin v placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for different results for different outcomes |
2 (124) | Symptom improvement | Pentosan polysulfate v placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, no intention-to-treat analysis, and for subjective assessment of outcome |
1 (100) | Quality of life | Pentosan polysulfate v placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (33) | Symptom improvement | Quercetin v placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data, and incomplete reporting of results. Consistency point deducted for different results for different outcomes |
1 (20) | Symptom improvement | Transurethral microwave thermotherapy v sham treatment | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, and for subjective outcome measurement |
1 (20) | Quality of life | Transurethral microwave thermotherapy v sham treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for sparse data, and incomplete reporting of results |
2 (276) | Symptom improvement | Oral antimicrobial drugs v placebo | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for too few comparators and for uncertainty about generalisability of results |
1 (81) | Symptom improvement | Prostatic massage plus antimicrobial drugs v antimicrobial drugs alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Biofeedback
Training that helps people to consciously change the vital functions of the body, such as heart rate, which are normally controlled unconsciously.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Meares–Stamey
The Meares–Stamey test involves collection of four sequential urine samples. Two are taken before prostatic massage; the first from the initial 10 ml and the second from the mid-stream urine. After prostatic massage, the expressed prostatic secretions are collected, as is the initial 10 ml of urine passed after massage. When bacteria and/or inflammatory cells are significantly higher in the two samples after prostatic massage, the pathology is considered to be specific to the prostate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- NIH classification system
Category I: acute bacterial prostatitis is an acute infection of the prostate. Category II: chronic bacterial prostatitis is a recurrent infection of the prostate. Category III: chronic non-bacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS), where there is no demonstrable infection. Subgroups of this class are: (A) inflammatory CPPS (leucocytes seen in semen, prostatic fluid, or urine after prostatic massage); and (B) non-inflammatory CPPS (no leucocytes seen). Category IV: asymptomatic inflammatory prostatitis, no subjective symptoms but leucocytes found in prostate/prostatic secretions during work up for other disorders (e.g. on prostate biopsy for prostate cancer).
- National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI)
Includes nine items across three domains: pain (4 items; 0–21), urinary symptoms (2 items; 0–10), and quality of life impact (3 items; 0–12). In all domains, higher scores indicate worse outcomes.
- Prostatic massage
Digital pressure applied to the prostate through the rectum.
- Sitz bath
A warm water bath taken in the sitting position. The water covers only the hips and buttocks.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Dr Bradley A Erickson, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, USA.
Dr Anthony J Schaeffer, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, USA.
Brian Van Le, Deptartment of Urology, Northwestern University Medical Centre, Chicago, USA.
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