Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Basing a Treatment Strategy on Randomized Placebo Controlled Trials 2012

Transcription

1 Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Basing a Treatment Strategy on Randomized Placebo Controlled Trials 2012 J. Curtis Nickel Professor of Urology, Queen s University Canada CIHR Canada Research Chair in Urologic Pain and Inflammation A WAY FORWARD Diagnosis Classification Treatment

2 Classification CAT 1 Acute Bacterial Prostatitis CATII Chronic Bacterial Prostatitis CAT III Chronic Prostatitis/Chronic Pelvic Pain Syndrome Cat IIIA Inflammatory Cat IIIB Non-inflammatory CAT IV Asymptomatic Prostatitis Epidemiology Prevalence Impact 2

3 The Clinical Picture UPOINT URINARY TENDERNESS PSYCHOSOCIAL NEUROGENIC/ SYSTEMIC ORGAN CENTRIC INFECTION 3

4 UPOINT The real clinical picture 1. Urinary Symptoms 2. Psychosocial 3. Organ Specific (Prostate or Bladder) 4. Infection 5. Neurologic/Systemic 6. Tenderness of Muscles Initial Evaluation History (Mandatory 4:C)) The NIH-CPSI instrument (Recommended 3:A) Physical examination (Mandatory 4:C) 4-glass or 2-glass test for WBC count and culture. (Recommended 3:A) Semen analysis and culture. (Not recommended 3:D) Flow rate, post-void residual and other urodynamic studies. (Optional 3:C) Serum PSA. (Not recommended 3:B) Routine imaging of the prostate. (Not recommended 3:D) Cystoscopy. (Not recommended 4:D) Psychological evaluation in selected patients. (Optional 3:B) CUA Guidelines, CUAJ,

5 Traditional Approach 2012 Approach UPOINT Diagnosis 5

6 UPOINT Phenotypes Realistic Diagnostic Strategy History Focused Physical Examination Condition specific Questionaires CPSI Focused questions (or questionnaire) for depression, catastrophizing, abuse, associated conditions (IBS, FM, CFS etc) Urinalysis and Culture (PPMT) Optional Cysto, Urodynamics, Psychosocial evaluation UPOINT Domain UPOINT IN CP/CPPS Study 1 N=100 Prevalence (%) Study 2 N=50 Study 3 N=1219 Study 4 N=100 Urinary Psychosocial Organ Specific Infection Neurologic/systemic Tenderness Urol 2009; 2. Scand J Urol Nephrol; 3. J Urol; 4. Urol

7 7

8 Highest Impact Domains Psychosocial Neurologic/Systemic Tenderness ALL DOMAINS OUTSIDE THE PROSTATE! Treatment 8

9 23 studies Traditional Therapies Antibiotic therapy for newly diagnosed, antimicrobial naïve patients. (Recommended 4:D) Antibiotic therapy for patients who have failed previous antibiotic therapy (Not recommended 1:A) Alpha-blocker as first line mono-therapy (Not recommended 1:A ) Alpha-blocker therapy for newly diagnosed, alpha-blocker naïve patients with voiding symptoms as part of a multi-modal treatment strategy (Optional 1:A) Anti-inflammatory monotherapy (Not-recommended 1:B) Anti-inflammatory therapy as part of a multimodal treatment strategy (Optional 2:C) The phytotherapies quercetin and pollen extract (recommended 2:B ) but are likely most effective as a part of a multimodal treatment strategy (3:C) Five alpha-reductase inhibitor monotherapy. (Not recommended 1:A) Five alpha-reductase inhibitor therapy in older men with lower urinary tract symptoms and/or as part of a multimodal treatment strategy (Optional 2:C)) Individualized multimodal therapy directed towards to defined clinical phenotype. (Recommended 3:C) Minimally invasive therapies such as TUNA, laser therapies, etc. (Not recommended 2:A) Invasive surgical therapies such as TURP and radical prostatectomy. (Not recommended 4:D) 9

10 Potential therapies Heat therapy in the form of microwave or ESW Biofeedback Physical therapy Psychotherapy (Mandatory for severe depression and/or suicidal tendencies) Acupuncture Electromagnetic stimulation Muscle relaxants (diazepam, baclofen, cyclobenzaprine) Neuromodulating agents (gabapentinoids, tricyclic antidepressants) Pudendal nerve modulation Surgery Traditional Therapeutic Approach to CP 10

11 23 studies a-blockers + antibiotics n = * * Glycosaminoglycan n = * (2 studies) * -9.70* * a-blockers n = * (1 study) (2 studies) (1 study) Pregabalin n = * (4 studies) (1 study) (2 studies) -8.44* Placebo n = * * (1 study) -6.84* -6.39* -9.84* (3 studies) Antibiotics n = (1 study) (2 studies) Finasteride n = Anti-inflammatory n = Phytotherapy n = 83 efigure 3. Network meta-analysis of total symptom scores 11

12 a-blockers n = (2 studies) Antibiotics n = 113 a-blockers + antibiotics n = (2 studies) (2 studies) 1.26* (5 studies) Pregabalin n = Finasteride n = (1 study) (1 study) 1.32 (1 studies) 1.21 Phytotherapy n = Anti-inflammatory n = 87 (1 study) 1.80* (3 studies) 1.13 Placebo n = * (1 study) efigure 7. Network meta-analysis of treatment responsiveness Updated Meta-analysis Alpha-blockers, Antibiotics, Anti-inflammatories 264 Studies 232 ineligible 32 potential studies 13 studies excluded 19 studies 12

13 3.9 Updated Network Meta-analysis 19 studies 1,689 CP/CPPS Patients TREATMENTS Alpha-blockers 395 Antibiotics 132 Anti-inflammatory 166 Alpha-blockers + Antibiotics 84 Placebo 661 N BJUI in press 2012 α-blockers n = Antibiotics n = * -9.7* -9.1* -2.9* Placebo n = * -13.6* -1.7* α-blockers + antibiotics n = * Anti-inflammatory n = 191 Figure 2. Network meta-analysis of total symptom scores 13

14 α-blockers n = Antibiotics n = * Placebo n = * α-blockers + antibiotics n = Anti-inflammatory n = 170 Figure 3. Network meta-analysis of treatment responsiveness INTERPRETATION Statistically significant, but modestly or barely clinically significant treatment effects Disconnect between overall benefit in entire population and individual responses 14

15 What have we learned? The traditional medical therapies can remain as part of our CP/CPPS treatment strategy Mono-therapy is not really very effective Phenotypically Directed Therapy will likely be the Key to Treatment Success UPOINT URINARY TENDERNESS PSYCHOSOCIAL NEUROGENIC/ SYSTEMIC ORGAN CENTRIC INFECTION 15

16 Phenotypic Approach (UPOINT) to CP/CPPS DOES UPOINT WORK? 100 consecutive men with CP/CPPS Clinically categorized according to UPOINT Treated according to algorithm Follow-up at least 6 months Urology

17 DOES UPOINT WORK? 100 consecutive men with CP/CPPS Clinically categorized according to UPOINT Treated according to algorithm Follow-up at least 6 months 6 point fall in CPSI 84% Total CPSI /-6.1 to 13.2+/-7.2 (p<0.0001) Impact of UPOINT directed Therapies on CPSI 17

18 The Future MAPP MIPPS Conclusion Our classical (traditional) therapies do work if we use them in an evidence- and rationalebased strategy 18