chronic prostatitis with chronic pelvic pain syndrome

Editorial: Chronic Prostatitis/Chronic Pelvic Pain Syndrome: It is time to change our management and research strategy

April 1, 2020/by J. Curtis Nickel

A urologist who manages patients with prostatitis (or for that matter, a patient suffering from the condition) would read the latest comprehensive review on pharmacologic interventions for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with despair. In the Cochrane Systemic review examining the available clinical evidence for the efficacy of pharmacological interventions for treating CP/CPPS, Franco et al [1] clearly show that low to very low quality evidence suggests that some treatments may confer at best, only a small and perhaps clinically insignificant benefit for patients. Are we doing something wrong?

To start with, we do not need to despair. We are now managing men with CP/CPPS much better, achieving clinically significant improvement in over 80% of patients [2,3]. This real world management success story, which continues to evolve, clearly shows much greater benefit than that suggested by all the clinical trials assessed in this review. Our similar independent patient data meta-analysis and comprehensive review of CP/CPPS management strategies [4] described very similar findings as that by Franco et al [1]. What intrigued us was the difference or the lack of correlation between overall symptom improvement (based on mean symptom score changes from baseline in the treated cohort of subjects compared to the placebo treated subjects) and the responder analyses which clearly showed some subjects had very significant responses despite the overall dismal mean symptom score differences in the entire population evaluated. We saw this consistently in our clinical trials and we see this in our day-to-day practice; some patients do well with an intervention and others fail miserably. Some of the problem lies in what we are measuring as outcomes in clinical treatment trials. The NIH Chronic Prostatitis Symptom Index (CPSI) is a composite score evaluating many different parameters (eg location, frequency and severity) and domains (pain, urinary and impact/quality of life) and while very useful to look at the clinical picture in each individual patient, should not be used as a primary endpoint or outcome of a clinical trial. The CPSI Pain domain is better but it still examines too many parameters (location, frequency and severity of pain). The NIH CPSI question #4, which is an NRS measurement of only pain severity, is in fact a validated outcome that can be compared between groups. However, CP/CPPS is much more complicated than just pain and that is why a patient driven subjective global assessment may be a more appropriate outcome, certainly in clinical practice. We need more CP/CPPS patient directed specific measurement tools to really assess the benefits of our treatments in individual patients, or at least in intervention-specific domains.

We now know the reason for this discrepancy between the overall population symptom score difference and the individual responder rate. We have learned that we cannot treat or manage CP/CPPS patients as a homogeneous group and hope that one treatment will benefit them all. We now know that the men suffering from CP/CPPS are a clinically heterogeneous group with different mechanisms of disease, spectrum of clinical symptoms and physical examination parameters. We have learned to identify the various clinical phenotypes based on a UPOINT categorization [5]. By assessing the contribution of urinary, psychosocial, organ specificity (eg prostate, penis, testes, etc), infection, neurogenic/neuropathic and tenderness of skeletal muscles (eg pelvic floor) contributions in each individual, we identify targets of intervention. These individualized multimodal treatment plans that we develop for each patient has led to clinical success in managing the majority of CP/CPPS patients [3,6]. In future we hope to understand the mechanisms for these phenotypes and develop biomarkers to better differentiate them.

What have I learned from Franco et al‘s comprehensive review of CP/CPPS treatments [1]? We must stop designing and performing these monotherapy treatment trials in which we enroll all subjects with a diagnosis of CP/CPPS. These type of clinical studies have been mainly driven by government regulatory rules in attempts to have drugs approved for CP/CPPS treatment. We should consider trial design where the patient eligibility criteria is definitive and clear enough so that we enroll only patients with a phenotype and/or mechanism that the specific therapy is directed towards – domain-specific trial design. Better yet, we must discover CP/CPPS biomarkers (urine, serum and/or prostate fluid) that will allow us to differentiate mechanisms and allow more effective directed therapy. We must consider more complicated and novel trial designs in which multimodal therapies can be assessed in different populations. I would propose a Multi-Intervention for Pelvic Pain Study (MIPPS) be designed and considered for CP/CPPS in which multimodal treatments designed for specific phenotype domains or disease mechanisms are evaluated in specific individuals. It is anticipated that such a real world experience study (designed to mimic real life clinical practice) would result in much better outcomes for patients. Going forward it is time to not only change our management approach, but also our research strategies.

by J. Curtis Nickel

References

1. Franco JVA, Turk T, Jung JH, Xiao Y, Iakhno S, Tirapegui F, et al. Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review. BJU Int. 2020; 125.

2. Shoskes DA, Nickel JC, Kattan M. Phenotypically Directed Multimodal Therapy for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Prospective Study Using UPOINT. Urol. 2010;75:1249-1253.

3. Doiron RC, Nickel JC. Management of chronic prostatitis/chronic pelvic pain syndrome. Can Urol Assoc J. 2018;12(6 Suppl 3):S161-S163

4. Anothaisintawee T, Attia J, Nickel JC, Thammakraisorn S, Numthavaj P, McEvoy M, Thakkinstian A. The Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A systematic review and network meta-analysis. JAMA. 2011;305:78-86.

5. Shoskes DA, Nickel JC, Rackley RR, Pontari MA. Clinical Phenotyping in Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Interstitial Cystitis: A Management Strategy for Urologic Chronic Pelvic Pain Syndromes. Prostate Cancer Prostatic Dis. 2009;12:177-83.

6. Shoskes D, DeWitt-Foy ME, Nickel JC. Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. European Urology Focus 2019;5: 2-4.

Video: Treatments for chronic prostatitis/chronic pelvic pain syndrome: a Cochrane review

April 1, 2020/by Juan V.A. Franco

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

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Abstract

Objective

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Patients and Methods

We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression.

Results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.

We found low‐ to very low‐quality evidence that α‐blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health – Chronic Prostatitis Symptom Index (NIH‐CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate‐ to low‐quality evidence indicates that 5α‐reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM‐89), pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Conclusions

Based on the findings of low‐ to very low‐quality evidence, this review found that some pharmacological interventions such as α‐blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

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Article of the Week: Diagnosis and treatment of CBP and CP/CPPS – a consensus guideline

October 14, 2015/by admin Z.9

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Jon Rees discussing his paper.

If you only have time to read one article this week, it should be this one.

Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline

Jon Rees, Mark Abrahams*, Andrew Doble† and Alison Cooper‡ for the Prostatitis Expert Reference Group (PERG)

Backwell and Nailsea Medical Group, Bristol, *Department of Pain Medicine, †Department of Urology, Addenbrooke’s Hospital, Cambridge, and ‡Evidence Team, Prostate Cancer UK, London, UK

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OBJECTIVES

To improve awareness and recognition of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among non-specialists and patients. To provide guidance to healthcare professionals treating patients with CBP and CP/CPPS, in both non-specialist and specialist settings. To promote efficient referral of care between non-specialists and specialists and the involvement of the multidisciplinary team (MDT).

PATIENTS AND METHODS

The guideline population were men with CBP or CP/CPPS (persistent or recurrent symptoms and no other urogenital pathology for ≥3 of the previous 6 months). Consensus recommendations for the guidelines were based on a search to identify literature on the diagnosis and management of CBP and CP/CPPS (published between 1999 and February 2014). A Delphi panel process was used where high-quality, published evidence was lacking.

RESULTS

CBP and CP/CPPS can present with a wide range of clinical manifestations. The four main symptom domains are urogenital pain, lower urinary tract symptoms (LUTS – voiding or storage symptoms), psychological issues and sexual dysfunction. Patients should be managed according to their individual symptom pattern. Options for first-line treatment include antibiotics, α-adrenergic antagonists (if voiding LUTS are present) and simple analgesics. Repeated use of antibiotics, such as quinolones, should be avoided if there is no obvious symptomatic benefit from infection control or cultures do not support an infectious cause. Early use of treatments targeting neuropathic pain and/or referral to specialist services should be considered for patients who do not respond to initial measures. An MDT approach (urologists, pain specialists, nurse specialists, specialist physiotherapists, general practitioners, cognitive behavioural therapists/psychologists, and sexual health specialists) is recommended. Patients should be fully informed about the possible underlying causes and treatment options, including an explanation of the chronic pain cycle.

CONCLUSION

Chronic prostatitis can present with a wide variety of signs and symptoms. Identification of individual symptom patterns and a symptom-based treatment approach are recommended. Further research is required to evaluate management options for CBP and CP/CPPS.

Editorial: Chronic prostatitis – how to give our best without apposite vagueness

October 14, 2015/by Antonella Giannantoni

A patient with chronic prostatitis poses a significant challenge to the urologist in everyday practice. We are certain that all readers will be familiar with the effort required to manage a man with chronic prostatitis, not only in diagnostic and therapeutic interventions but also personal and psychological support. This is particularly true, when you consider that chronic prostatitis affects men of all ages and can significantly impair their quality of life and social functioning. Starting with medical considerations, the symptomatic, chronic forms of prostatitis, as defined by the USA National Institutes of Health (NIH) are chronic bacterial prostatitis (CBP; NIH category II) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; NIH category III) [1]. These chronic conditions present with a wide range of clinical manifestations, but the four main primarily recognised symptoms are: urogenital pain, lower urinary tract symptoms (voiding or storage symptoms), alteration of the psychological status, and sexual dysfunction [2].

Prevalence rates are estimated at 2–10%, with some as high as 15–16% in Asian, European and North American samples [3]. Both CBP and CP/CPPS present with no one identified underlying cause, although infectious, genetic, anatomical, physiological, neurological, and immunological factors may be involved. For whatever reason, the underlying factor(s) of chronic prostatitis are likely to trigger tissue inflammation and immune responses which, in turn, induce bladder and pelvic pain leading to LUTS, ejaculatory pain, and pain in other regions, including the lower back and abdomen. The lack of a distinct aetiology has made making a specific diagnosis and effectively treating the disorder very arduous, presenting a serious challenge to urologists. In this respect, the difficulty for us is to do our best in trying to solve the problem, without apposite vagueness! [4]. In the obscurity of actual knowledge about the pathophysiology, diagnosis and treatment of CBP and CP/CPPS, it seems that recent insights can be favourably identified.

The consensus guideline on the diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome, published in BJUI by Rees et al. [5], indeed represents an important tool to provide guidance to urologists and healthcare professionals treating patients with CBP and CP/CPPS. Starting from a literature review of the most updated evidence-based information in the field of CBP and CP/CPPS, the consensus guideline provides new and useful recommendations in signs and symptoms evaluation, and clinical assessment and diagnosis of CBP and CP/CPPS. In this regard, reliable instruments, e.g. the NIH-Chronic Prostatitis Symptoms index (NIH-CPSI), IPSS and UPOINT (Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, and Tenderness) scales [5], have been suggested to assess initial symptom severity, evaluate phenotypic differences, and monitor patients’ response to therapeutic intervention. In addition, psychological screening to evaluate the presence of psychological disorders, e.g. depression and anxiety, has been strongly recommended. What is most important is the detailed information about treatment approaches for each individual patient, according to history, physical examination, investigations, and stage of the disease. Specifically, levels of evidence and different recommendations are provided for α-blockers, antimicrobial therapy, phytotherapy, and pain management. This guideline also has the merit of being simple and easily understandable for non-specialists and patients in showing the most appropriate way in following a patient with CBP and CP/CPPS. We are sure that this consensus guideline represents a step forward to a more adequate approach in diagnosing and treating patients with chronic prostatitis. It can be a tool to improve awareness and recognition of these conditions, and for uniformity among different specialists involved in the field.

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Antonella Giannantoni and Silvia Proietti*

Department of Surgical and Biomedical Sciences, Urolog y and Andrology Section, Ospedale S. Maria della Misericordia, University of Perugia, Perugia, and *Human itas Clinical and Research Centre, Department of Urology, Rozzano, Milan, Italy

References

1 Murphy AB, Macejko A, Taylor A, Nadler RB. Chronic prostatitis: management strategies. Drugs 2009; 69: 71–84

2 Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents 2008; 31 (Suppl. 1): S85–90

3 Habermacher GM, Chason JT, Schaeffer AJ. Prostatitis/chronic pelvic pain syndrome. Annu Rev Med 2006; 57: 195–206

4 Twain M. My Late Senatorial Secretaryship (written about 1867). In: Sketches New and Old. Hartford, CT, and Chicago, IL: The American Publishing Company, 1882. Available at: https://www.gutenberg.org/ﬁles/ 3189/old/orig3189-h/p3.htm. Accessed May 2015.

5 Rees J, Abrahams M, Doble A, Cooper A. Prostatitis Expert Reference Group (PERG). Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. BJU Int 2015; 116: 509–25

Video: CP and CPPS – a consensus guideline

October 14, 2015/by admin Z.9

Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline

Jon Rees, Mark Abrahams*, Andrew Doble† and Alison Cooper‡ for the Prostatitis Expert Reference Group (PERG)

Backwell and Nailsea Medical Group, Bristol, *Department of Pain Medicine, †Department of Urology, Addenbrooke’s Hospital, Cambridge, and ‡Evidence Team, Prostate Cancer UK, London, UK

Read the full article