Transcript Update on Prostatitis and Treatments

Update on Prostatitis and
Treatments
BAUN Benign Study Day
14/03/2012
Mr Richard Cetti
Specialist Registrar Urology, QA Portsmouth
Prostatitis an Important Problem!
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Prevalence 2.2-13.8%
 Quality of life
 Economic Costs
Prostatitis an Important Problem!
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‘Pain management is a necessity in the work of
each physician.’
F. Sauerbruch, 1936
Introduction
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Pain
Classification/Terminology
Presentation
Investigation
Treatment- historical, contemporary and the
evidence
The Future
Pain
-an unpleasant sensory and emotional experience
Hypogastric Nerve
Pelvic Nerves
Pudendal Nerve
Brain Ascending Syst
Convergence
Projection
Theory (Ruch)
Dorsal Horn
Periphery
Skin
Viscus
Chronic Pain
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Combination of:
Neuroplasticity
Central processing altered
Trophic changes in subcutaneous tissue and muscle
All site normal sensations become painful (allodynia).
At site painful stimuli become more painful
(hyperalgesia).
Zone affected adjacent tissue (secondary hyperalgesia).
Aetiology of Chronic Prostatitis
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Poorly understood
Multiple factors within and between patients
Hypotheses:
Presence of antibiotic resistant non-culturable micro-organisms
Chemical irritation
Intra-ductal reflux and obstruction
Dysfunctional high pressure voiding
Neuropathic pain
Pudendal nerve entrapment
Autoimmune
Classification
Classification- NIH/EAU
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Cat
Cat
Cat
Cat
I
II
III
IV
Acute bacterial prostatitis
Chronic bacterial prostatitis
Prostate Pain Syndrome (CPPS)
Asymptomatic inflammatory prostatitis
Classification- NIH/EAU
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Cat I
Cat II
Acute bacterial prostatitis
Chronic bacterial prostatitis
Cat III
Prostate 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 urine
IIIb- non-inflammatory
Cat IV
Evaluation
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3 main factors:
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Symptoms
 WBC’s
 Bacteria
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
IPSS
Chronic Prostatitis Symptom Index
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
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Meares-Stamey ‘4 Glass
Test’
1st 10-15ml of voided
urine VB1
MSU 10-15ml urine VB2
Prostate Massage- EPS
1st 10-15ml voided urine
post massage VB3
Modified: VB1 and VB3
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
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History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
‘Diagnosis of exclusion’
Treatment- Organcentric vs.
Snowflake
Traditional Organcentric Model
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Pathogenesis simple
Traditional Organcentric Model
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Pathogenesis simple
Infection
‘itis’
Inflammation
PAIN!
Traditional Organcentric Model
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Pathogenesis simple
Infection
‘itis’
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Inflammation
PAIN!
Antibiotics
Anti-inflammatories
Alpha blockers
Treatment simple?
Antibiotics
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Ciprofloxacin, 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 improvement
Trial 2 weeks and continue for 6 if benefit.
Alpha-blockers
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Alfuzosin, Terazosin, Tamsulosin
N 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.
CPSI responders
Placebo
N=134
Alfuzosin
N=138
66(49%)
68(49%)
Anti-inflammatories
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Celecoxib, rofecoxib
J 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 Painkillers
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Amitriptylline, Pregabalin
Arch 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.
CPSI Responders
Placebo
N=106
Pregabalin
N=218
38(36%)
103(47.2%)
So are we getting desperate?
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Laparoscopic prostatectomy for chronic
prostatitis
This study is currently recruiting participants.
Verified by the Krongrad Institute Oct 2008.
ClinicalTrials.gov identifier: NCT00775515
UPOINT
Urinary
Tenderness
Psychosocial
Neurogenic/Systemic
Organcentric
Infection
UPOINT
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Retrospective study of 90 CPPS patients seen by
one Urologist over 12 months
Domain
Percentage
Urinary
52
Psychosocial
34
Organ Specific
61
Infection
16
Neurogenic/Systemic
37
Tenderness
53
The Future: Patient-centric treatment.
‘Phenotyping’
Novel Therapies
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Cernilton
Eur 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, placebocontrolled 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.
CPSI Responders
Placebo
N=69
Cernilton
N=70
50%
71%
Take Home Points
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Poorly understood aetiology/pathogenesis.
Heterogenous disease.
Established treatments perform poorly in RCT’s.
Phenotyping patient and treatment.
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‘Active exclusion, Active Inclusion’
‘Active exclusion, Active Inclusion’
‘Active exclusion, Active Inclusion’