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Update on Prostatitis and TreatmentsBAUN Benign Study Day14/03/2012Mr Richard CettiSpecialist Registrar Urology, QA Portsmouth
Prostatitis an Important Problem!
Prevalence 2.2-13.8%Quality of lifeEconomic Costs
Prostatitis an Important Problem!
Pain management is a necessity in the work of each physician. F. Sauerbruch, 1936
IntroductionPainClassification/TerminologyPresentationInvestigationTreatment- historical, contemporary and the evidenceThe Future
Pain-an unpleasant sensory and emotional experience Hypogastric NervePelvic NervesPudendal NerveSkinViscusConvergence Projection Theory (Ruch)
Chronic PainCombination of:NeuroplasticityCentral processing alteredTrophic changes in subcutaneous tissue and muscleAll site normal sensations become painful (allodynia).At site painful stimuli become more painful (hyperalgesia).Zone affected adjacent tissue (secondary hyperalgesia).
Aetiology of Chronic ProstatitisPoorly understoodMultiple factors within and between patientsHypotheses:Presence of antibiotic resistant non-culturable micro-organismsChemical irritationIntra-ductal reflux and obstructionDysfunctional high pressure voidingNeuropathic painPudendal nerve entrapmentAutoimmune
Classification
Classification- NIH/EAUCat IAcute bacterial prostatitisCat IIChronic bacterial prostatitisCat IIIProstate Pain Syndrome (CPPS)Cat IVAsymptomatic inflammatory prostatitis
Classification- NIH/EAUCat IAcute bacterial prostatitisCat IIChronic bacterial prostatitisCat IIIProstate Pain Syndrome (CPPS)Discomfort or pain in the pelvic region for at least 3 months with variable voiding and sexual symptoms, no demonstrable infection.IIIa- inflammatory PPS- white cells in semen/eps/post eps urineIIIb- non-inflammatoryCat IV
Evaluation3 main factors:
SymptomsWBCsBacteria
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationChronic Prostatitis Symptom IndexIPSS
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationMeares-Stamey 4 Glass Test1st 10-15ml of voided urine VB1MSU 10-15ml urine VB2Prostate Massage- EPS1st 10-15ml voided urine post massage VB3Modified: VB1 and VB3
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
EvaluationHistoryFocused ExaminationCondition Specific QuestionnairesUrinalysis and CultureSemen cultureOptional: PSA, Urinary Cytology, US, Cystoscopy, Urodynamics, Psychosocial evaluation
Evaluation
Diagnosis of exclusion
Treatment- Organcentric vs. Snowflake
Traditional Organcentric ModelPathogenesis simple
Traditional Organcentric ModelPathogenesis simpleInfectionitisInflammationPAIN!
Traditional Organcentric ModelPathogenesis simpleAntibioticsAnti-inflammatoriesAlpha blockersTreatment simple?InfectionitisInflammationPAIN!
AntibioticsCiprofloxacin, ofloxacin, levofloxacin~10% patients will have culturable bacteria.J Urol. 2001 May;165(5):1539-44. Predictors of patient response to antibiotic therapy for the chronic prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical trial. Nickel JC et al.However, 57% of patients on ofloxacin saw improvementTrial 2 weeks and continue for 6 if benefit.
Alpha-blockersAlfuzosin, Terazosin, TamsulosinN Engl J Med. 2008 Dec 18;359(25):2663-73. Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome Nickel JC et al.Multicenter, randomized, double-blind, placebo-controlled trial of alfuzosin.272 men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin/day or placebo.The primary outcome was a reduction of at least 4 points in the CPSI score.
Anti-inflammatoriesCelecoxib, rofecoxibJ Urol. 2003 Apr;169(4):1401-5. A randomized, placebo controlled, multicenter study to evaluate the safety and efficacy of rofecoxib in the treatment of chronic nonbacterial prostatitis. Nickel JC et al.Multicenter, randomized, double-blind, placebo-controlled trial of rofecoxib.161 men were randomly assigned to treatment with either 25-50 mg of rofecoxib/day or placebo.Of the patients, 79% on 50 mg rofecoxib versus 59% on placebo reported no or mild pain. But not statistically significant.
Neuropathic PainkillersAmitriptylline, PregabalinArch Intern Med. 2010 Sep 27;170(17):1586-93. Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. Pontari MA et al.Multicenter, randomized, double-blind, placebo-controlled trial of pregabalin.218 men were randomly assigned to treatment for 6 weeks with either 150-600 mg of pregabalin/day or placebo.The primary outcome was a reduction of at least 6 points in the CPSI score.
So are we getting desperate?Laparoscopic prostatectomy for chronic prostatitis
This study is currently recruiting participants.Verified by the Krongrad Institute Oct 2008.ClinicalTrials.gov identifier: NCT00775515
UPOINTUrinaryPsychosocialOrgancentricInfectionNeurogenic/SystemicTenderness
UPOINTRetrospective study of 90 CPPS patients seen by one Urologist over 12 months
The Future: Patient-centric treatment. Phenotyping
Novel TherapiesCerniltonEur Urol. 2009 Sep;56(3):544-51. A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis-chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo-controlled phase 3 study. Wagenlehner FM et al.Multicentre, prospective, randomised, double-blind, placebo-controlled trial in men with CP/CPPS (NIH IIIA)Primary end-point, defined as a decrease of the CPSI total score by at least 25% or at least 6 points.
Take Home PointsPoorly understood aetiology/pathogenesis.Heterogenous disease.Established treatments perform poorly in RCTs.Phenotyping patient and treatment.
Active exclusion, Active Inclusion
Active exclusion, Active Inclusion
Active exclusion, Active Inclusion
Convergence Projection Theory (Ruch)