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379Cooled thermotherapy (TUMT) for chronic abacterial prostatitis — 2 years after treatment
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378
THALIDOMIDE AS T H E R A P Y F O R T H E CHRONIC PELVIC P A I N S Y N D R O M E (CPPS)
CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME RECURRENCE AFTER INITIAL EFFECTIVE PHYTOTHERAPEUTIC TREATMENT
Guercini F., Costantini E., Pajoncini C., Giannantoni A., Porena M. Reissigl A.1, Pointner J. 1, Obwexer S. 1, Wiunig C. 1, Aigner M. t, Meyer-Venter R. 1, Remzi M. 2, Djavan B. 2
University of Peragia, Urology, Perugia, Italy INTRODUCTION & OBJECTIVES: Many reports suggested that chronic abacterial Type 3A prostatitis may have an auteimmune origin with an abnormal reaction of the prostate parenchyma to some bacteria such as Chlamydia Tracomatis or Mycoplasmata, which are hard to detect. Abnormal levels of several cytokines (IL2, IL6, IL8, IL 10 and TNFcQ in sperm have been linked with prostatic autoimmunity. Cytnkine modulating drags include INFLIXIMAB, ETANERCEPT and THALIDOMIDE, the first two of which are associated with severe side effects. As thalidomide is not associated with serious side effects in men we decided to assess the efficacy of oral thalidomide therapy as therapy for suspected autoimmune chronic prostatitis in a double-blind randomised trial. MATERIAL & METHODS: Thirty patients aged between 18 and 65 years old were recruited to the study which was approved by the Perugia University Ethics Committee. Inclusion criteria were chronic abacterial prostatitis associated with abnormal sperm cytokine levels (IL2, 6, 8, l0 and TNFcQ as measured by a commercial Kit Quanti Flow. Exclusion criteria were signs of peripheral neuropathy and blood concentrations of bilirubin, and other liver function indices three times higher than normal. Patients were randomised to two groups of 15. After signing a detailed informed consent form, all patients underwent the NIH Chronic Prostatitis Symptom Score (NtH-CPSI) was assessed in all. Patients in group A received oral Thalidomide (100 rag/daily) for 4 weeks, which was increased to 200 mg/daily during the following 8 weeks of treatment. Patients in group B were given placebo which was administered in the same modality. At 4, 12 and 16 weeks follow-up, cytokines were measured in sperm and the NIH-CPSI score was assessed again in both groups. Data analysis was performed using the Mann-Whitney test to compare the NIH-CPS scores and cytokine levels in Group A vs. Group B at baseline and at 4, 12, 16 weeks follow-up. Statistical significance was set at p<0.05. RESULTS: Baseline: The median NIH-CPSI score was 34 in Group A and 36 in Group B. Median IL2 level was 220 in both groups. Median IL6 was 260 in group A and 95 in Group B. Median IL8 was >2.000 in both groups and mean ILl0 was <3.9 in both groups. Median TNFc~ was 12 in group A and 8 in Group B. After thalidomide therapy:fly different in the two groups at 4, 12 and 16 weeks follow up. In patients in Group A all cytokine levels were significantly reduced at 4, 8 and 12 weeks follow up as compared to baseline levels. No significant differences were observed in Group B. Side effects: 2 patients (1 in Group A and 1 in group B) developed signs of peripheral neuropathy and were excluded from the study. CONCLUSIONS: This double-blind randomised study shows that at the administered dose Thalidomide does not provide relief of symptoms associated with CPPS, despite a significant reduction in cytokine levels in sperm.
ILKH-Bregenz, Urology, Bregenz, Austria, 2AKH-Vienna, Urology, Vienna, Austria I N T R O D U C T I O N & O B J E C T I V E S : Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common life burden condition effecting many men. Patients with CP/CPPS category IIIB initially treated with Serenoa repens (Permixon) in a prospective placebo-controlled multicenter trial were re-evaluated 3 years after treatment. M A T E R I A L & METHODS: Men with category IIIB CPPS were primarily randomized to Pernaixon and matched with a placebo-control group. The response to therapy was evaluated at 6 and 12 months. 3 years later, a follow-up study was conducted to re-evaluate efficacy parameters including Patients Subjective Giobal Assessment (SGA), the total NIH Chronic Prostatitis Symptom Index (CPSI), the pain, voiding and quality of life/impact domains of the CPSI, safety data, PSA and prostate volume. R E S U L T S : 55 of 72 men (average age 40.5, range 28-52) had a 3-year follow-up evaluation after initial treatment with Permixon. Follow-up outcomes were compared with the initial response to therapy based on efficacy parameters. The initially observed decrease in total NIH-CPSI, pain, quality of life domain and voiding could not be confirmed ad 3 year follow-up visit. By 6 and 12 months 78.2% and 71.8% (initial visits) had at least m i l d i m p r o v e m e n t (30-50% improvement) o f SGA + NIH-CPSI versus 32.4% at follow-up evaluation after 3 years. A clear, clinically significant improvement in total NIH-CPSI (50% or greater improvement) of 52.6% and 44.2% as reported at initial visits decreased to 19%, respectively. PSA-values and prostate volume slightly increased from baseline.
CONCLUSIONS: The initially encouraging study results suggesting that Permixon provides clinical benefit in patients with category IIIB CP/CPPS could not be confirmed 3 years after treatment. This study clearly shows that a treatment strategy based on a short time monotherapy does not have a continuous effect in patients with CP/CPPS.
379
380
COOLED THERMOTHERAPY (TUMT) FOR CHRONIC ABACTERIAL PROSTATITIS - 2 YEARS AFTER TREATMENT Kastner C. 1, Miller E l, Fletcher H. ~, Nelson C?, Austin L.2
TRANSRECTAL MICROWAVE THERMOTHERAPY WITH ADEN-4 (RUSSIA) F O R S Y M P T O M A T I C T R E A T M E N T O F C H R O N I C A B A C TERIAL PROSTATITIS: RANDOMISED BLIND SHAM CONTROLLED STUDY
~East Surrey Hospital, Urology, Redhill, United Kingdom, 2Urologix Inc., Clinical Research, Mirmeapolis, United States
Abdullin 1.1, Apolikhin 0 . 2, Prosyanikov y.2
INTRODUCTION & OBJECTIVES: We previously presented and published 6-month and 1-year follow-up results of a multi-center prospective feasibility study using Cooled TUMT with the Targis® System from Urologix, Inc. for chronic abacterial prostatitis / chronic pelvic pain syndrome (CP/CPPS) classified as NIH IIIA& B. Complete follow-up data after 2 years is now available from East Surrey Hospital (ESH). MATERIAL & METHODS: Patients diagnosed with intractable CP/CPPS and symptoms for more than 3 out of 6 months prior to treatment (NIH-CPSI Pain Score > 8) received Cooled TUMT that achieved estimated peak interstitial temperatures of ~55°C or ~70°C. Tolerability, side effects and efficacy were measured with standard diagnostic tests and NIH-CPSI questiormaires. Three patients received re-treatments after 1 year of follow-up according to their original treatment protocols. RESULTS: 39 Patients completed treatment and were followed for 1 year. Due to increased treatment discomfort compared to BPH patients, analgesia was adjusted for CP/CPPS resulting in good tolerability. Mean changes in NIH-CPSI scores from baseline to 6/12 months were: Pain 11.5 vs. 3.4/4.6; Urinary 4.7 vs. 2.3/3.1; quality of life (QOL) 7.2 vs. 3.0/3.8; Total 23.4 vs. 8.7/11.5 (all p<0.0001 except Urinary). Complications were minimal and transient and reported previously. All 15 patients from ESH completed 2-year follow-up, with the following baseline vs. 24-month NIH-CPSI scores: Pain 9.7 vs. 5.2; Urinary 4.1 vs. 3.0; QOL 6.9 vs. 4.1; Total 20.7 vs. 12.3 (all p<0.005 except Urinary). The table below shows the proportion of patients at least 50% improved over baseline. 3 ESH patients requested re-treatment after initial improvement and then symptom recurrence. Symptom-free periods were longer after re-TUMT; 1 patient has achieved continuous reliefto date, 1 experienced episodic recurrence of symptoms and 1 suffered a severe episode of acute )rostatitis similar to previous episodes. No additional complications were noted. Patients 50% improved over baseline NIH-CPSI-Pain NIH-CPSI Urinary
NIH-CPSI-QOL NIH-CPSI-TOTAL
6 months ALL
12 months ALL
6 months ESH only
12 months ESH only
24 months ESH only
77% 50% 69% 69%
63% 43% 54% 54%
71% 36% 47% 57%
62% i5% 31% 38%
67% 27% 53% 47%
CONCLUSIONS: Efficacy of Targis for intractable CP/CPPS is comparable or better than previously reported for TUMT and other treatment modalities with good durability. Side effects remain temporary and minor. Longer follow-up and a furore larger trial are required to further evaluate efficacy and placebo effect.
1Institute of Urology, SM-Clinic, Moscow, Russia, 2Institute o f Urology, Scientific, Moscow, Russia I N T R O D U C T I O N & O B J E C T I V E S : Chronic abacterial prostatitis (Chronic pelvic pain syndrome) is very common condition in middle age males. Due to unknown causes of this condition the treatment options are very limited. The effectiveness of different types of physiotherapeutie options lacks good evidence. In our study we investigated the effectiveness transrectal microwave thermotherapy produced by A D E N - 4 (Russia) in randomised blind sham controlled study.
MATERIAL & METHODS: The blind sham controlled randomised study was carried out in 57 males aged 29-52 years, mean age 42 year, with diagnosed chronic abacterial prostatitis. The patients with bacterial prostatitis, benign prostate hyperplasia and suspicion on cancer o f prostate were excluded. Patients were divided into 2 groups by randomisation. Patients did not know to which group they were concerned. Patients in transrectal microwave group underwent microwave thermotherapy: 42C for i hour by ADEN-4 for five times every two days. Patients in control group underwent simulation of therraotherapy by ADEN4 with the same schedule. The severity of symptoms before and one month after treatment was assessed with NIH-CPSI. A d v e r s e effects were recorded. Differences of estimated parameters were tested by Student t-test. R E S U L T S : Due to randomisation patients were divided into 2 groups: 29 males in treatment and 28 males in control. The differences in male age and NIH-CPSI in groups were not statistically significant. Mean NIH-CPSI in both groups was 22.0 +/-5. After one month the mean NIH-CPSI was significantly lower in treatment group than in control 9.0 +/-3 and 14.0 +/-4, respectively, p<0.00l. N o b o d y of all patients had complaints on adverse effects of microwave thermotherapy or its simulation. C O N C L U S I O N S : Transrectal microwave thermotherapy with ADEN-4 could be effective and safe option for patients with abacterial prostatitis.
European Urology Supplements 4 (2005) No. 3, pp. 97
378
THALIDOMIDE AS T H E R A P Y F O R T H E CHRONIC PELVIC P A I N S Y N D R O M E (CPPS)
CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME RECURRENCE AFTER INITIAL EFFECTIVE PHYTOTHERAPEUTIC TREATMENT
Guercini F., Costantini E., Pajoncini C., Giannantoni A., Porena M. Reissigl A.1, Pointner J. 1, Obwexer S. 1, Wiunig C. 1, Aigner M. t, Meyer-Venter R. 1, Remzi M. 2, Djavan B. 2
University of Peragia, Urology, Perugia, Italy INTRODUCTION & OBJECTIVES: Many reports suggested that chronic abacterial Type 3A prostatitis may have an auteimmune origin with an abnormal reaction of the prostate parenchyma to some bacteria such as Chlamydia Tracomatis or Mycoplasmata, which are hard to detect. Abnormal levels of several cytokines (IL2, IL6, IL8, IL 10 and TNFcQ in sperm have been linked with prostatic autoimmunity. Cytnkine modulating drags include INFLIXIMAB, ETANERCEPT and THALIDOMIDE, the first two of which are associated with severe side effects. As thalidomide is not associated with serious side effects in men we decided to assess the efficacy of oral thalidomide therapy as therapy for suspected autoimmune chronic prostatitis in a double-blind randomised trial. MATERIAL & METHODS: Thirty patients aged between 18 and 65 years old were recruited to the study which was approved by the Perugia University Ethics Committee. Inclusion criteria were chronic abacterial prostatitis associated with abnormal sperm cytokine levels (IL2, 6, 8, l0 and TNFcQ as measured by a commercial Kit Quanti Flow. Exclusion criteria were signs of peripheral neuropathy and blood concentrations of bilirubin, and other liver function indices three times higher than normal. Patients were randomised to two groups of 15. After signing a detailed informed consent form, all patients underwent the NIH Chronic Prostatitis Symptom Score (NtH-CPSI) was assessed in all. Patients in group A received oral Thalidomide (100 rag/daily) for 4 weeks, which was increased to 200 mg/daily during the following 8 weeks of treatment. Patients in group B were given placebo which was administered in the same modality. At 4, 12 and 16 weeks follow-up, cytokines were measured in sperm and the NIH-CPSI score was assessed again in both groups. Data analysis was performed using the Mann-Whitney test to compare the NIH-CPS scores and cytokine levels in Group A vs. Group B at baseline and at 4, 12, 16 weeks follow-up. Statistical significance was set at p<0.05. RESULTS: Baseline: The median NIH-CPSI score was 34 in Group A and 36 in Group B. Median IL2 level was 220 in both groups. Median IL6 was 260 in group A and 95 in Group B. Median IL8 was >2.000 in both groups and mean ILl0 was <3.9 in both groups. Median TNFc~ was 12 in group A and 8 in Group B. After thalidomide therapy:fly different in the two groups at 4, 12 and 16 weeks follow up. In patients in Group A all cytokine levels were significantly reduced at 4, 8 and 12 weeks follow up as compared to baseline levels. No significant differences were observed in Group B. Side effects: 2 patients (1 in Group A and 1 in group B) developed signs of peripheral neuropathy and were excluded from the study. CONCLUSIONS: This double-blind randomised study shows that at the administered dose Thalidomide does not provide relief of symptoms associated with CPPS, despite a significant reduction in cytokine levels in sperm.
ILKH-Bregenz, Urology, Bregenz, Austria, 2AKH-Vienna, Urology, Vienna, Austria I N T R O D U C T I O N & O B J E C T I V E S : Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common life burden condition effecting many men. Patients with CP/CPPS category IIIB initially treated with Serenoa repens (Permixon) in a prospective placebo-controlled multicenter trial were re-evaluated 3 years after treatment. M A T E R I A L & METHODS: Men with category IIIB CPPS were primarily randomized to Pernaixon and matched with a placebo-control group. The response to therapy was evaluated at 6 and 12 months. 3 years later, a follow-up study was conducted to re-evaluate efficacy parameters including Patients Subjective Giobal Assessment (SGA), the total NIH Chronic Prostatitis Symptom Index (CPSI), the pain, voiding and quality of life/impact domains of the CPSI, safety data, PSA and prostate volume. R E S U L T S : 55 of 72 men (average age 40.5, range 28-52) had a 3-year follow-up evaluation after initial treatment with Permixon. Follow-up outcomes were compared with the initial response to therapy based on efficacy parameters. The initially observed decrease in total NIH-CPSI, pain, quality of life domain and voiding could not be confirmed ad 3 year follow-up visit. By 6 and 12 months 78.2% and 71.8% (initial visits) had at least m i l d i m p r o v e m e n t (30-50% improvement) o f SGA + NIH-CPSI versus 32.4% at follow-up evaluation after 3 years. A clear, clinically significant improvement in total NIH-CPSI (50% or greater improvement) of 52.6% and 44.2% as reported at initial visits decreased to 19%, respectively. PSA-values and prostate volume slightly increased from baseline.
CONCLUSIONS: The initially encouraging study results suggesting that Permixon provides clinical benefit in patients with category IIIB CP/CPPS could not be confirmed 3 years after treatment. This study clearly shows that a treatment strategy based on a short time monotherapy does not have a continuous effect in patients with CP/CPPS.
379
380
COOLED THERMOTHERAPY (TUMT) FOR CHRONIC ABACTERIAL PROSTATITIS - 2 YEARS AFTER TREATMENT Kastner C. 1, Miller E l, Fletcher H. ~, Nelson C?, Austin L.2
TRANSRECTAL MICROWAVE THERMOTHERAPY WITH ADEN-4 (RUSSIA) F O R S Y M P T O M A T I C T R E A T M E N T O F C H R O N I C A B A C TERIAL PROSTATITIS: RANDOMISED BLIND SHAM CONTROLLED STUDY
~East Surrey Hospital, Urology, Redhill, United Kingdom, 2Urologix Inc., Clinical Research, Mirmeapolis, United States
Abdullin 1.1, Apolikhin 0 . 2, Prosyanikov y.2
INTRODUCTION & OBJECTIVES: We previously presented and published 6-month and 1-year follow-up results of a multi-center prospective feasibility study using Cooled TUMT with the Targis® System from Urologix, Inc. for chronic abacterial prostatitis / chronic pelvic pain syndrome (CP/CPPS) classified as NIH IIIA& B. Complete follow-up data after 2 years is now available from East Surrey Hospital (ESH). MATERIAL & METHODS: Patients diagnosed with intractable CP/CPPS and symptoms for more than 3 out of 6 months prior to treatment (NIH-CPSI Pain Score > 8) received Cooled TUMT that achieved estimated peak interstitial temperatures of ~55°C or ~70°C. Tolerability, side effects and efficacy were measured with standard diagnostic tests and NIH-CPSI questiormaires. Three patients received re-treatments after 1 year of follow-up according to their original treatment protocols. RESULTS: 39 Patients completed treatment and were followed for 1 year. Due to increased treatment discomfort compared to BPH patients, analgesia was adjusted for CP/CPPS resulting in good tolerability. Mean changes in NIH-CPSI scores from baseline to 6/12 months were: Pain 11.5 vs. 3.4/4.6; Urinary 4.7 vs. 2.3/3.1; quality of life (QOL) 7.2 vs. 3.0/3.8; Total 23.4 vs. 8.7/11.5 (all p<0.0001 except Urinary). Complications were minimal and transient and reported previously. All 15 patients from ESH completed 2-year follow-up, with the following baseline vs. 24-month NIH-CPSI scores: Pain 9.7 vs. 5.2; Urinary 4.1 vs. 3.0; QOL 6.9 vs. 4.1; Total 20.7 vs. 12.3 (all p<0.005 except Urinary). The table below shows the proportion of patients at least 50% improved over baseline. 3 ESH patients requested re-treatment after initial improvement and then symptom recurrence. Symptom-free periods were longer after re-TUMT; 1 patient has achieved continuous reliefto date, 1 experienced episodic recurrence of symptoms and 1 suffered a severe episode of acute )rostatitis similar to previous episodes. No additional complications were noted. Patients 50% improved over baseline NIH-CPSI-Pain NIH-CPSI Urinary
NIH-CPSI-QOL NIH-CPSI-TOTAL
6 months ALL
12 months ALL
6 months ESH only
12 months ESH only
24 months ESH only
77% 50% 69% 69%
63% 43% 54% 54%
71% 36% 47% 57%
62% i5% 31% 38%
67% 27% 53% 47%
CONCLUSIONS: Efficacy of Targis for intractable CP/CPPS is comparable or better than previously reported for TUMT and other treatment modalities with good durability. Side effects remain temporary and minor. Longer follow-up and a furore larger trial are required to further evaluate efficacy and placebo effect.
1Institute of Urology, SM-Clinic, Moscow, Russia, 2Institute o f Urology, Scientific, Moscow, Russia I N T R O D U C T I O N & O B J E C T I V E S : Chronic abacterial prostatitis (Chronic pelvic pain syndrome) is very common condition in middle age males. Due to unknown causes of this condition the treatment options are very limited. The effectiveness of different types of physiotherapeutie options lacks good evidence. In our study we investigated the effectiveness transrectal microwave thermotherapy produced by A D E N - 4 (Russia) in randomised blind sham controlled study.
MATERIAL & METHODS: The blind sham controlled randomised study was carried out in 57 males aged 29-52 years, mean age 42 year, with diagnosed chronic abacterial prostatitis. The patients with bacterial prostatitis, benign prostate hyperplasia and suspicion on cancer o f prostate were excluded. Patients were divided into 2 groups by randomisation. Patients did not know to which group they were concerned. Patients in transrectal microwave group underwent microwave thermotherapy: 42C for i hour by ADEN-4 for five times every two days. Patients in control group underwent simulation of therraotherapy by ADEN4 with the same schedule. The severity of symptoms before and one month after treatment was assessed with NIH-CPSI. A d v e r s e effects were recorded. Differences of estimated parameters were tested by Student t-test. R E S U L T S : Due to randomisation patients were divided into 2 groups: 29 males in treatment and 28 males in control. The differences in male age and NIH-CPSI in groups were not statistically significant. Mean NIH-CPSI in both groups was 22.0 +/-5. After one month the mean NIH-CPSI was significantly lower in treatment group than in control 9.0 +/-3 and 14.0 +/-4, respectively, p<0.00l. N o b o d y of all patients had complaints on adverse effects of microwave thermotherapy or its simulation. C O N C L U S I O N S : Transrectal microwave thermotherapy with ADEN-4 could be effective and safe option for patients with abacterial prostatitis.
European Urology Supplements 4 (2005) No. 3, pp. 97