Update on Prostatitis and

Treatments

BAUN Benign Study Day

14/03/2012
Mr Richard Cetti
Specialist Registrar Urology, QA
Portsmouth

Prostatitis an Important
Problem!

Prevalence 2.2-13.8%
Quality of life
Economic Costs

Prostatitis an Important
Problem!

Pain management is a necessity in the

work of each physician.
F. Sauerbruch, 1936

Introduction

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

Convergenc
e Projection
Theory
(Ruch)

Brai
n

Ascending
Syst

Dorsal
Horn

Periphery
Skin
Viscus

Chronic Pain

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

Poorly understood
Multiple factors within and between patients
Hypotheses:
Presence of antibiotic resistant non-culturable microorganisms
Chemical irritation
Intra-ductal reflux and obstruction
Dysfunctional high pressure voiding
Neuropathic pain
Pudendal nerve entrapment
Autoimmune

Classification

Classification- NIH/EAU

Cat I
Cat II
Cat III
Cat IV

Acute bacterial prostatitis

Chronic bacterial prostatitis
Prostate Pain Syndrome (CPPS)
Asymptomatic inflammatory prostatitis

Classification- NIH/EAU

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

3 main factors:

Symptoms
WBCs
Bacteria

Evaluation

History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics,
Psychosocial evaluation

Evaluation

History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics,
Psychosocial evaluation

Evaluation

History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics,
Psychosocial evaluation

Evaluation

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

History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics,
Psychosocial evaluation

Evaluation

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

History
Focused Examination
Condition Specific Questionnaires
Urinalysis and Culture
Semen culture
Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics,
Psychosocial evaluation

Evaluation

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

Pathogenesis
simple

Traditional Organcentric
Model

Pathogenesis
simple
Infection
itis

Inflammation

PAIN!

Traditional Organcentric
Model

Pathogenesis
simple
Infection
itis

Inflammation

PAIN!

Antibiotics
Anti-inflammatories
Alpha blockers
Treatment simple?

Antibiotics

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

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

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

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?

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

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

Cernilton
Eur Urol. 2009 Sep;56(3):544-51. A pollen extract
(Cernilton) in patients with inflammatory chronic prostatitischronic 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.

CPSI Responders

Placebo
N=69

Cernilton
N=70

50%

71%

Take Home Points

Poorly 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