Definitions for the level of evidence (1-4) and grade of recommendation (A-C) are provided at the end of the "Major Recommendations."
Background
Introduction to Chronic Urogenital Pain Syndromes
Basic investigations must be undertaken to rule out 'well-defined' pathologies. If the results are negative, a 'well-defined' pathology is unlikely. Any further investigations should be done only for specific indications, e.g., for subdivision of a pain syndrome.
The definitions for chronic urogenital pain syndromes are based on the recommendation for terminology laid down by the International Continence Society (ICS) and follow the axial structure of the International Association for the Study of Pain (IASP) classification (see Tables 1 and 2 in the original guideline document).
An Algorithm for Chronic Pelvic Pain Diagnosis and Treatment
The algorithm for diagnosing and treating chronic pelvic pain (CPP) (see Figure 1 in the original guideline document) has been written to guide a physician through the process from diagnosis to management. A physician should follow steps 1 to 6 (see Table below), while referring to the correct column in the algorithm. Further guidance on which diagnostic tools should be used in specific pain locations is provided in different chapters of the original guideline document.
Table. Step-by-step Guidance on Using the Algorithm* for Diagnosis and Treatment of CPP |
Step |
Action |
1 |
Start by considering the organ system where the symptoms appear to be primarily perceived |
2 |
'Well-defined' conditions, such as cystitis, should be diagnosed and treated according to national or international guidelines |
3 |
When treatment has no effect on the pain, additional tests (e.g., cystoscopy or ultrasound) should be performed |
4 |
When these tests reveal any pathology, this should be treated appropriately |
5 |
If treatment has no effect, the patient should be referred to a pain team |
6 |
If no well-defined condition is present or when no pathology is found by additional tests, the patient should also be referred to a pain team |
The only aspect of diagnosis that is specific for CPP is where the pain is localized. However, because pain is perceived in structures related to the pelvis, this has led to many organ-specific, but often not well-defined, local disease syndromes.
Because CPP is pain perceived in structures related to the pelvis, it is necessary to approach diagnosis of a patient with CPP as a chronic pain patient. Confining the diagnosis to a specific organ may overlook multisystem functional abnormalities requiring individual treatment and general aspects of pain in planning investigation and treatment.
For the above reasons, the guideline authors advocate early involvement of a multidisciplinary pain team. In practice, this should mean that well-known diseases, e.g., 'true' cystitis and endometriosis, will be diagnosed and treated early. If treating such conditions does not reduce symptoms, or such well-defined conditions are not found, then further investigation may be necessary, depending on where the pain is localized.
It should be noted, however, that over-investigation may be as harmful as not performing appropriate investigations. The European Association of Urology (EAU) algorithms introduce the concept of the 'minimum investigations' required to exclude a well-defined condition.
Chronic Prostate Pain/Chronic Prostatitis Associated with Chronic Pelvic Pain Syndrome (CP/CPPS)
Definition
Chronic prostatitis associated with chronic pelvic pain syndrome (CP/CPPS) is discomfort or pain in the pelvic region over a minimum of 3 months, with sterile specimen cultures and either significant, or insignificant, white blood cell counts in prostate-specific specimens (i.e., semen, expressed prostatic secretions and urine collected after prostate massage). The disease is referred to as 'prostate pain syndrome (CP/CPPS)' throughout the rest of this chapter.
Diagnosis
Despite its name, prostate pain syndrome (CP/CPPS) is a symptomatic diagnosis, which is diagnosed from a 3-month history of genitourinary pain and an absence of other lower urinary tract pathologies (see above). Determination of the severity of disease, its progression and treatment response can be assessed only by means of a validated symptom-scoring instrument. Quality of life should also be measured because it can be as poor as in acute myocardial infarction, unstable angina pectoris or Crohn's disease. Reliable, valid indexes of symptoms and quality of life are the National Institutes of Health (NIH) Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (I-PSS). These subjective outcome measures are recommended for the basic evaluation and therapeutic monitoring of patients in urological practice and have been translated and validated for many European languages.
In prostate pain syndrome (CP/CPPS), urodynamic studies demonstrate decreased urinary flow rates, incomplete relaxation of the bladder neck and prostatic urethra, as well as abnormally high urethral closure pressure at rest. The external urethral sphincter is normal during urination.
Laboratory diagnosis has been classically based on the four-glass test for bacterial localization ('gold standard'). Besides a sterile pre-massage urine (voided bladder urine-2 [VB2], CP/CPPS shows less than 10,000 colony-forming units of uropathogenic bacteria in expressed prostatic secretions (EPS) and insignificant numbers of leucocytes or bacterial growth in ejaculate. However, this test is too complex for use by practising urologists. Diagnostic efficiency may be enhanced cost-effectively by a simple screening procedure, i.e., the two-glass test or pre-post-massage test (PPMT). In an extensive analysis of both tests, PPMT was able to indicate the correct diagnosis in more than 96% of patients.
A general algorithm for diagnosis and treatment of chronic prostatic pain is shown in Figure 2 of the original guideline document.
Treatment
Because of the unknown cause of prostate pain syndrome (CP/CPPS), many therapies used are based on anecdote. Most patients require multimodal treatment aimed at the main symptoms and taking comorbidities into account. In the past few years, results from randomized controlled trials (RCTs) have led to advances in standard and novel treatment options. Graded recommendations are given in the table below.
Table. Treatment of Prostate Pain Syndrome (CP/CPPS)
|
Level of Evidence |
Grade of Recommendation |
Comment |
|
1a |
A |
Effect on total NIH-CPSI |
|
3 |
C |
Only very limited data |
|
3 |
B |
Quinolones
If previously untreated (naïve) only, reassess after 2-3 weeks. Duration 4-6 weeks
|
|
3 |
C |
As part of multimodal therapy for treatment-refractory pain in collaboration with pain clinics |
- Non-steroidal anti-inflammatory drugs
|
1b |
B |
Long-term side effects have inflammatory drugs to be considered |
- Steroids
- Immunosuppressive agents
|
3 |
Not recommended |
Not outside clinical trials |
- 5-alpha-reductase inhibitors
|
1b |
B |
If benign prostatic hyperplasia is present |
|
1b-3 |
B |
|
- Biofeedback, relaxation exercise
- Lifestyle changes
- Massage therapy
- Chiropractor therapy
- Acupuncture
- Meditation
|
2a-3 |
B |
As supportive, second-line therapies |
|
1b |
C |
Not outside clinical trials |
- Transrectal hyperthermia
- Transurethral thermotherapy
|
3 |
C |
|
- Transurethral incision of the bladder neck
- Transurethral resection of the prostate
- Radical prostatectomy
|
3 |
Not recommended in general |
Specific additional indication required |
Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC)
Introduction
It is very important to realise that IC is a heterogeneous spectrum of disorders, which are still poorly defined, and that inflammation is an important feature in only a subset of patients. To embrace all patients suffering from bladder pain, the terms painful bladder syndrome (PBS) or bladder pain syndrome (BPS) have been suggested as more accurate terminology. This terminology assumes that IC represents a special type of chronic inflammation of the bladder, while PBS or BPS refers to pain in the bladder region. The term bladder pain syndrome of BPS will be used in these guidelines.
Diagnosis
The diagnosis of BPS is made using symptoms, examination, urine analysis, cystoscopy with hydrodistension and biopsy (see Figure 3 in the original guideline document). Patients present with characteristic pain and urinary frequency, which is sometimes extreme and always includes nocturia.
The character of the pain is the key symptom of the disease:
- Pain is related to the degree of bladder filling, typically increasing with increasing bladder content.
- It is located suprapubically, sometimes radiating to the groins, vagina, rectum or sacrum.
- Pain is relieved by voiding but soon returns.
The differences between the two IC subtypes include clinical presentation and age distribution, and they may be discriminated non-invasively. The two subtypes respond differently to treatment and express different histopathological, immunological and neurobiological features.
Classic IC is a destructive inflammation with some patients eventually developing a small-capacity fibrotic bladder or upper urinary tract outflow obstruction. There is no such progression in non-ulcer disease. Endoscopically, classic IC displays reddened mucosal areas often associated with small vessels radiating towards a central scar, sometimes covered by a small clot or fibrin deposit. The scar ruptures with increasing bladder distension, producing a characteristic waterfall-type of bleeding. There is a strong association between classic IC and reduced bladder capacity under anaesthesia.
Medical Treatment
A summary of the treatment options for BPS/IC, including a rating of the level of evidence and grade of recommendation is given in the tables 'Medical Treatment of BPS/IC' and 'Intravesical, Interventional, Alternative and Surgical Treatment of BPS/IC' below. Figure 3 in the original guideline document provides a flowchart for the diagnosis and therapy of BPS/IC based on the information discussed above.
Table. Medical Treatment of BPS/IC
|
Level of Evidence |
Grade of Recommendation |
Comment |
Analgesics |
2b |
C |
Indications limited to cases awaiting further treatment |
Corticosteroids |
3 |
C |
Corticosteroids not recommended as long-term treatment |
Hydroxyzine |
1b |
A |
Standard treatment, even though limited efficacy shown in randomized controlled trial (RCT) |
Cimetidine |
1b |
B |
Insufficient data |
Amitriptyline |
1b |
A |
Standard treatment |
Sodium pentosan polysulphate sodium (PPS) |
1a |
A |
Standard treatment
Data contradictory
|
Antibiotics |
1b |
A |
Limited role in the treatment of interstitial cystitis (IC) |
Prostaglandins |
3 |
C |
Insufficient data on IC, adverse effects |
L-arginine |
1b |
C |
Effect in IC uncertain |
Cyclosporin A |
1b |
A |
RCT: superior to PPS but more adverse effects |
Duloxetine |
2b |
C |
No effect, tolerability poor |
Oxybutynin/tolterodine |
3 |
C |
Limited indication in IC
|
Gabapentin |
3 |
C |
Preliminary data so far |
Suplatast tosilate |
3 |
C |
Preliminary data so far |
Quercetin |
3 |
C |
Preliminary data so far |
Table. Intravesical, Interventional, Alternative and Surgical Treatment of BPS/IC
|
Level of Evidence |
Grade of Recommendation |
Comment |
Intravesical anaesthesia |
3 |
C |
|
Intravesical pentosan polysulphate sodium (PPS) |
1b |
A |
|
Intravesical heparin |
3 |
C |
|
Intravesical hyaluronic acid |
2b |
B |
|
Intravesical chondroitin sulphate |
2b |
B |
|
Intravesical dimethyl sulphoxide (DMSO) |
1b |
A |
|
Intravesical bacillus Calmette-Guérin |
1b |
Not recommended |
|
Intravesical clorpactin |
3 |
Not recommended |
Obsolete |
Intravesical vanilloids |
1b |
C |
Data contradictory |
Bladder distension |
3 |
C |
|
Electromotive drug administration |
3 |
B |
|
Transurethral resection (coagulation and LASER) |
NA |
A/B |
Hunner's lesions only |
Nerve blockade/epidural pain pumps |
3 |
C |
For crisis intervention; affects pain only |
Sacral neuromodulation |
3 |
B |
Not recommended beyond clinical trials |
Bladder training |
3 |
B |
Patients with little pain |
Manual and physical therapy |
3 |
B |
|
Diet |
3 |
C |
|
Acupuncture |
3 |
C |
Data contradictory |
Hypnosis |
|
No data |
|
Psychological therapy |
3 |
B |
|
Surgical treatment |
NA |
A |
Largely varying data ultima ratio, experienced surgeons |
NA = type of evidence not applicable, since RCTs are unethical in such surgical procedures.
Scrotal Pain
An algorithm for diagnosing and managing scrotal pain is provided in Figure 4 of the original guideline document.
A physical examination should always be done in patients with scrotal pain. Gentle palpation of each component of the scrotum is performed to search for masses and for painful spots. A digital rectal examination (DRE) is done to look for prostate abnormalities and examine the pelvic floor muscles. Scrotal ultrasound has limited value in finding the cause of the pain.
If physical examination is normal, ultrasound is sometimes performed to reassure the patient that there is no tumour in the testis. Ultrasound can be used to diagnose hydroceles, spermatoceles, cysts and varicoceles. The urine should be analysed. Magnetic resonance imaging and computed tomography scans may be used to help with assessment.
Recommendations for the treatment of scrotal pain syndrome are listed in the table below.
Table. Treatment of Scrotal Pain Syndrome
|
Level of Evidence |
Grade of Recommendation |
Comment |
Orchiectomy |
1a |
A |
In case of intratesticular tumour |
Excision |
3 |
B |
Hydrocele or varicocele |
Antibiotics |
3 |
C |
For up to 3 months |
Surgical intervention |
3 |
C |
Epididymectomy, denervation spermatic cord
Vasovasostomy
|
Pelvic floor muscle therapy |
1b |
A |
Including trigger point treatment |
Urethral Pain Syndrome
Positive diagnostic signs are urethral tenderness or pain on palpation and a slightly inflamed urethral mucosa found during endoscopy.
In clinical practice, the diagnosis of urethral pain syndrome is commonly given to patients who present with the symptoms of dysuria (with or without frequency, nocturia, urgency and urge incontinence) in the absence of evidence of urinary infection. The 'absence of urinary infection' cause diagnostic problems as the methods typically used to identify urinary infection are extremely insensitive. Dysuria is pain or discomfort experienced in association with micturition. The classical symptom of a burning sensation in the urethra during voiding caused by infection is well known. The external dysuria experienced by women with vaginitis when urine passes over the labia is less appreciated.
Biochemical testing and microbiological culture of urine is important in assessing lower urinary tract symptoms and has been reviewed in some detail in the elderly.
There is confusion about the concept of significant bacteriuria. This may be accepted as 105 colony-forming units (CFU) of a single species in asymptomatic women. However, it may be as low as 102 CFU of a single species of a known urinary pathogen in symptomatic women. Many automated culture systems have a sensitivity of 104 CFU, while urinary leucocyte esterase and nitrite tests are correlated only with cultures as high as 105 CFU. In addition, many laboratory culture systems detect only just over 50% of infections in midstream urine specimens from genuinely infected patients.
Although rarely included, proper manual urine microscopy using a haemocytometer should be part of a definitive work-up. Nowadays, most laboratories screen urine in wells using inverted microscopes or rely on robotic detection of pyuria, which are both insensitive methods. This is regrettable because studies have shown that significant pyuria is a nearly universal indicator of urinary tract infection, although it is not specific for differentiating cystitis from urethritis, particularly urethritis due to Chlamydia trachomatis. In relation to the latter, dysuria also merits the microscopic examination of a urethral smear after it has been Gram stained. If present, a purulent urethral exudate will be obvious, although a causative micro-organism will be identified in less than 50% of cases.
Urethral trauma arising from intercourse may cause pain and dysuria. Women with pelvic floor dysfunction sometimes describe similar symptoms, as do post-menopausal women, in whom trauma is associated with oestrogen deficiency, loss of lubrication and vaginal dryness.
Unless a thorough assessment is carried out, bearing in mind the comments described above, the diagnosis of urethral pain syndrome does not seem credible.
Treatment
There is no consensus on treatment. Management may require a multidisciplinary approach. Various modalities including antibiotics, alpha-blockers, acupuncture and laser therapy have been proved successful. Psychological support is important. An algorithm for diagnosing and managing urethral pain syndrome is given in Figure 5 of the original guideline document.
Definitions
Levels of Evidence
1a Evidence obtained from meta-analysis of randomized trials
1b Evidence obtained from at least one randomized trial
2a Evidence obtained from one well-designed controlled study without randomization
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities
Grades of Recommendations
- Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomized trial
- Based on well-conducted clinical studies, but without randomized clinical studies
- Made despite the absence of directly applicable clinical studies of good quality