Approach

This topic covers chronic pelvic pain localised to/centred around the prostate of non-bacterial origin. Bear in mind, however, that chronic pelvic pain syndromes are closely linked and are difficult to separate in clinical practice.

Treatment of primary prostate pain syndrome (PPPS) is based on the bio-psycho-social model, which encompasses the multidimensional aspects of a chronic pain disorder. Healthcare professionals should take a holistic approach to address the complexity of the problem and patients should be offered multimodal and phenotypically directed treatment options that address their relevant physical, emotional, and psychosocial issues.[4][51][52] It is also important that the treatment strategy includes elements of self-management that encourage patients to be actively involved. Providing information and treatment options that are tailored to the patient's problems and enabling them to express their beliefs and concerns is an effective way to reduce anxiety.[72] Patient preference should also be taken into consideration when determining initial treatment choices, which may be medical management or non-pharmacological interventions.

Single interventions are rarely effective on their own for managing PPPS. Combinations of pharmacological and non-pharmacological interventions have a higher chance of improving the patient's condition, especially if therapeutic interventions are tailored to the individual.[4][6]​ Some experts also recommend treatment of symptoms that may overlap with other pelvic pain syndromes, for example, empirical treatment options such as anti-cholinergics in patients with storage symptoms.

It is also important to manage patient expectations before initiating a management plan. If the likely outcome of treatment is exaggerated, there is a significant risk that the patient will be disappointed if there is little improvement in their symptoms.

If patients continue to have symptoms despite exhausting the available options for treatment, consider referral to chronic pain centres, occupational therapy, and pain psychology professionals as appropriate.

There is no evidence for surgical intervention, including transurethral incision of the bladder neck, radical transurethral resection of the prostate, or, in particular, radical prostatectomy, in the management of chronic pain in patients with PPPS (i.e., without an underlying cause of symptoms, such as bladder outlet obstruction due to bladder neck obstruction or prostatic outflow obstruction).[4][6][50]

Patient education

Educate all patients about the nature of pain and address any fears they may have about undetected disease.[4]

  • Ensuring patients are given appropriate information and that they understand their condition underpins self-management and adherence to agreed treatments. This can also give patients a sense of control and empowerment that can lead to a decrease in the intensity and unpleasantness of the pain itself.[4][73][74]

Encourage patients to remain physically active.[4][50][74]

  • As well as having general health benefits, exercise may reduce pain and improve quality of life.[75]

  • One study involving 85 participants found that a physical activity programme caused a small reduction of prostatitis-related symptoms compared with the control group (NIH‐CPSI score mean difference ‐2.50, 95% CI ‐4.69 to ‐0.31).[76]

Pharmacological treatment

Few studies have investigated medications used to treat chronic primary pelvic pain syndromes. Where no treatment option is available specifically for PPPS, a more general approach can be taken drawing on what is known about the effects of drugs used for other types of chronic pain and neuropathic pain.[74][77] It is also important to point out the large discrepancy between treatment effects reported in case series and controlled trials in patients with chronic pelvic pain. This is mostly due to a large placebo effect (usually around 40%) or publication bias.

When choosing pharmacological treatments, consider the type and severity of the patient’s symptoms and the effects on their lifestyle, the benefits of each treatment, possible adverse effects and interactions with existing medications, the patient’s comorbidities, and the concerns and expectations of the patient.[77]

Combinations of treatments often provide greater benefit than when used in isolation, and should be tailored to the individual patient based on their symptoms and preferences.[4][6] Combinations of treatments may also allow lower doses of individual drugs to be given and therefore reduce the likelihood of adverse effects.

Consider referring patients with complex chronic pain conditions to a centre specialising in pain management. Indications may include pain that is severe and refractory to treatment with analgesics, or pain that significantly impairs the patient’s ability to participate in daily activities.[6][77]

Targeted pharmacological treatments

Alpha-blockers

Offer treatment with a uroselective alpha-blocker (e.g., alfuzosin, tamsulosin, silodosin) to men with PPPS who have concomitant voiding symptoms.[4][6] Uroselective alpha-blockers are preferred to reduce the risk of potential adverse effects.[6][50]

  • Alpha-blockers have a moderate effect on total pain, voiding, and quality of life scores in people with PPPS.[4] A network meta-analysis of several randomised controlled trials of alpha-blockers has shown significant improvement in overall symptoms, pain, voiding ability, and quality of life.[12] However, a more recent systematic review noted that although treatment with alpha-blockers may lead to some reduction of symptoms, the durability of the effect is not entirely clear.[78]

Antibiotics

Consider a trial of empirical antibiotics, initially for 4 to 6 weeks, in antibiotic-naive patients with PPPS.[4][6][78] Antibiotics may be effective in patients with PPPS via treatment of an unknown uropathogen, or due to an anti-inflammatory effect.[50] Antibiotics have a moderate effect on total pain, voiding, and quality of life scores in patients with PPPS.[4] However, the evidence base for treatment of patients with antibiotics is weak and somewhat conflicting, and care must be taken to avoid unnecessary antibiotic use.

  • A meta-analysis of randomised controlled trials found that antibiotics had some beneficial effect in patients with PPPS, including improvement of symptoms.[12]

  • A more recent Cochrane review of 5 studies (372 participants) of low quality of evidence found that fluoroquinolones may reduce prostatitis symptoms compared with placebo and are probably not associated with an increased incidence in adverse events. It also concluded that antibiotics probably result in little to no difference in sexual dysfunction and quality of life.[78]

If antibiotics are given, guidelines recommend a fluoroquinolone (e.g., ciprofloxacin) or a tetracycline (e.g., doxycycline); however, the choice should be guided by local resistance patterns.[4][6][50] Follow your local protocols.

  • Note that fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[79] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycaemia, and mental health adverse effects in patients taking fluoroquinolones.[80][81]

Offer other therapeutic options after one unsuccessful treatment course with an antibiotic.[4]

Pentosan polysulfate sodium

Consider pentosan polysulfate sodium in patients with pain associated with storage symptoms, such as urgency and frequency.[4] However, European guidelines note that this recommendation is based on low-quality evidence, and the drug is not routinely used for this indication in the US.

  • Pentosan polysulfate sodium is a semi-synthetic drug used in the treatment of interstitial cystitis.

  • One study of 100 patients with PPPS showed that the group treated with pentosan polysulfate sodium showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (-2.0 or 22% vs. -1.0 or 12%, P=0.031).[82]

  • It is important to consider the potential benefits of treatment alongside risk of adverse effects, which may include nausea, diarrhoea, headache, and altered liver function.[83] Note also that cases of pigmentary maculopathy have been reported rarely in patients treated with pentosan polysulfate sodium, especially after long-term use at high doses. Healthcare professionals are advised that patients should have baseline and regular ophthalmic examinations before and during treatment, and to consider stopping treatment if pigmentary maculopathy develops. Patients should be advised to seek immediate medical attention if visual changes occur.[84][85]

Pain management

Paracetamol

Give regular doses of paracetamol to patients with early-stage PPPS for the management of pain symptoms.[6][50] Paracetamol is generally considered to be the preferred first-line analgesic, but can be used in combination with other analgesics if paracetamol alone is not sufficiently managing pain symptoms.[50] There is little evidence for the efficacy of paracetamol in many pain conditions.[83] Assess individual response when deciding on long-term use.[4]

Non-steroidal anti-inflammatory drugs (NSAIDs)

Consider an NSAID for pain management in patients with PPPS whose symptoms may be due to peripheral inflammatory processes or in patients who experience inflammatory flare.[6] Take into account the higher incidence of adverse effects with prolonged use of this medication class.[4][78]

NSAIDs are often used for pelvic pain, although there is little evidence to support their use.

  • One overview review of 16 systematic reviews and four individual patient data meta-analyses of standard doses in different painful conditions concluded that ibuprofen often provided superior pain relief when compared with paracetamol.[83] The anti-inflammatory effect may be helpful if persistent peripheral inflammatory processes are suspected in association with chronic pelvic pain.

  • In another meta-analysis, anti-inflammatory drugs (such as celecoxib) were 80% more likely to have a favourable treatment response than placebo in patients with PPPS.[86] However, the treatment effect may be limited to the duration of therapy as long-term efficacy is not known.

There is no evidence that one NSAID is superior to another.[4] NSAIDs should only be offered for short-term treatment of pain, and patients should be reviewed regularly with monitoring for adverse effects (which may limit use).[6] Discontinue if there is no improvement of symptoms within 4-6 weeks of treatment.[6]

NSAIDs are associated with an increased risk of cardiovascular thrombotic events and gastrointestinal toxicity (bleeding, ulceration, perforation). Therefore, NSAIDs should be used at the lowest effective dose for the shortest effective treatment course.

Neuromodulators

In patients with neuropathic pain whose pain persists following initial treatment with paracetamol or an NSAID, switch to a neuromodulator.[6][77] Neuromodulators should be given in the context of a regular and long-term treatment plan. Although the efficacy of neuromodulators in chronic pelvic pain syndromes has not been clearly established, they have been proven to be effective in other chronic pain conditions.[87][88]

If nociceptive pain or an inflammatory route is considered to be the cause of pain, simple analgesics and NSAIDs may be continued alongside neuromodulator treatment.[6]

Initial treatment options include an antidepressant (e.g., amitriptyline, duloxetine) or a gabapentinoid (e.g., gabapentin, pregabalin).[6][77][89][90] If the initial treatment is not effective or is not tolerated, switch to a different neuromodulator. Consider switching again if the second and third neuromodulators tried are also not effective or not tolerated.[6][77]

Titrate the dose against the response and adverse effects.[4] Note that patients who are considered for gabapentinoids should be evaluated for a history of drug misuse before prescribing, and followed up with observation for signs of misuse and dependence.[74]

Opioids

Refer patients with continued pain refractory to treatment and that significantly impairs their ability to participate in daily activities to a centre specialising in pain management for consideration of treatment with opioids.[4][6]

  • Opioids should be avoided as first-line use in patients presenting in early stages of PPPS due to the risk of opioid dependency.[6]

  • Opioids should be used as part of a broader treatment plan and only by doctors experienced in their use.

There are very few data available on the use of opioid analgesics in patients with PPPS.

Physical therapy

Refer patients with pelvic floor pathology or myofascial pain to a specialist physiotherapist for targeted treatment of pelvic floor pathology or for more general treatment of myofascial pain.[4][50] Because of the low risk of adverse effects, myofascial treatments may be offered as an initial therapy option.[4]

  • Evidence suggests that the symptoms of PPPS may result from pelvic muscle tenderness and spasm.[24][25] Specialist physical therapy and techniques that encourage relaxation and coordinated use of the pelvic floor muscles may therefore help to improve symptoms.[6]

  • Patients with chronic pelvic pain and pelvic floor muscle dysfunction may benefit from learning to relax the muscles when the pain starts, as this may allow them to break the vicious cycle of pain-cramp-pain.

  • Repetitive or chronic muscular overuse can activate trigger points (hyperirritable sites within a taut band) in the muscle, which are often found in patients with chronic pelvic pain. Physical therapy treatments that target these trigger points can have a positive effect on the pain.

Specialist physical therapeutic interventions that may also be considered include acupuncture and extracorporeal shockwave therapy.

Acupuncture

  • Consider treatment with acupuncture to help improve symptoms and quality of life.[4][6][50][74][75]

  • A review of three studies concluded that acupuncture probably leads to a clinically meaningful reduction in prostatitis symptoms compared with sham procedure (mean difference [MD] in total NIH‐CPSI score ‐5.79, 95% CI ‐7.32 to ‐4.26), with little to no difference in adverse events.[75] Two systematic reviews and a meta-analysis of seven randomised controlled trials comparing acupuncture with sham control or oral medical treatment concluded that acupuncture is effective and safe, and significantly reduces symptom scores compared with control groups.[91][92]

Extracorporeal shockwave therapy

  • Several small sham controlled randomised studies have reported improvements in pain and NIH-CPSI scores with perineal extracorporeal shockwave therapy compared with simulated procedures/control groups.[93][94] Two recent systematic reviews and meta-analyses have concluded that extracorporeal shockwave therapy is effective for the improvement of pain and quality of life over the short term, but long-term data are lacking.[78][95]

Psychological therapy

Assess patients with PPPS for psychosocial symptoms, and refer for cognitive behavioural therapy (CBT) or to a psychologist experienced in treating pain if these are suspected to be contributing to the patient’s condition.[6][50][74] Psychological therapy can be targeted at the pain itself to reduce its impact on life, or at adaptation to pain to improve mood and function and reduce healthcare use with or without pain reduction.

  • Although there is very limited evidence from studies to support the use of psychological interventions such as CBT, its use as part of a multicomponent therapeutic may reduce associated distress and improve quality of life and the patient's ability to self-manage and function. One small non-randomised controlled feasibility trial involving 60 participants with chronic pelvic pain found that patients receiving a combination of physical therapy and CBT had a small and non-significant intervention effect in health-related quality of life, but significant effects regarding depression severity and pain.[96]

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