Timo Marttila

Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome : A double-blind, placebo-controlled, pilot study

OBJECTIVES To investigate whether treatment of inflammatory chronic pelvic pain syndrome (ICPPS) with finasteride has any influence on symptoms associated with ICPPS. METHODS Forty-one patients with ICPPS were randomized (1:3) to treatment with either placebo (25%, n = 10) or finasteride 5 mg daily (75%, n = 31 ) for 1 2 months. Efficacy was evaluated by analysis of symptomatic improvement through responses to symptom questionnaires, pain evaluation on an analytical visual scale, analgesic use as reported in patient diaries, urine flow and residual volume, and prostate volume. RESULTS Prostatitis Symptom Severity Index and prostatism scores dropped significantly in patients in the finasteride group (P < 0.001 and P < 0.05, respectively). There were no statistically significant differences in pain between the groups. There were significant differences in the changes of prostate volume and in serum prostate-specific antigen concentrations between the finasteride and placebo groups (P < 0.03 and P < 0.02, respectively). The groups did not differ with regard to side effects. CONCLUSIONS Our results indicate that finasteride has an effect in ICPPS. The mechanisms by which finasteride works in these patients are unclear and could not be solved in this pilot study, which had relatively few patients. A further trial with larger numbers is required to confirm these results.

HUMAN COMPLEMENT FACTOR H RELATED PROTEIN TEST FOR MONITORING BLADDER CANCER

PURPOSE The BTA stat test is a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine. We compared BTA stat test to voided urine cytology in patients monitored for bladder cancer in a prospective trial, and determined whether this test is effective in detection of recurrence not seen by regular cystoscopy. MATERIALS AND METHODS A total of 445 consecutive patients with bladder cancer were studied. A voided urine sample was obtained before cystoscopy and divided for culture, cytology and BTA stat testing. In cases of a positive BTA stat test but negative cystoscopy, excretory urography or renal ultrasound, random biopsies and collected ureteral urine samples for ureteral cytology were obtained. The overall sensitivity and specificity as well as positive and negative predictive values for BTA stat test, cytology and their combination were calculated. RESULTS Of the 445 patients 118 (26.5%) had bladder cancer recurrence on cystoscopy, which was detected by BTA stat test and cytology in 63 (53.4%) and 21 (17.8%), respectively. Of the remaining 327 patients not having recurrent tumor on cystoscopy 81 (24.8%) had a positive BTA stat test. Excretory urography or renal ultrasound and random biopsies in 48 (59.3%) of these patients revealed 7 recurrences, making the total number of recurrent tumors 125 of 412 (30.3%). The overall sensitivities and specificities for the BTA stat test, cytology and their combination were 56.0%, 19.2%, 60.0% and 85.7%, 98.3% and 85.0%, respectively. CONCLUSIONS The sensitivity for detection of recurrent tumor on BTA stat test is superior to that of voided urine cytology in all bladder cancer categories, whereas the specificity of voided urine cytology is higher than that for BTA stat test. However, a sixth of the patients with apparent false-positive BTA stat test results chosen for further investigation had recurrent tumors that were not found on routine cystoscopy. Although the sensitivity and specificity were highest when both tests were used, the differences were not significant overall. Therefore, the BTA stat test could potentially replace urine cytology for followup of superficial bladder cancer.

SENSITIVITY OF HUMAN COMPLEMENT FACTOR H RELATED PROTEIN (BTA STAT) TEST AND VOIDED URINE CYTOLOGY IN THE DIAGNOSIS OF BLADDER CANCER

PURPOSE We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

Herpes simplex virus, cytomegalovirus, and papillomavirus DNA are not found in patients with chronic pelvic pain syndrome undergoing radical prostatectomy for localized prostate cancer.

OBJECTIVES To study the possible involvement of viruses in chronic pelvic pain syndrome (CPPS) using polymerase chain reaction. Among other factors, the involvement of viruses in CPPS has been speculated, but few studies have investigated this. METHODS Consecutive patients with localized prostate cancer for whom radical prostatectomy was considered were evaluated for symptoms of CPPS using the National Institutes of Health Chronic-Prostatitis Symptom Index. Ten patients with moderate to severe symptoms and 10 without symptoms were included in the study. The presence of herpes simplex virus (types 1 and 2), cytomegalovirus, and human papillomavirus DNA was investigated by polymerase chain reaction in prostatic tissue samples obtained at radical prostatectomy. RESULTS All the samples were negative for the viral sequences tested. CONCLUSIONS A viral etiology could not be demonstrated in CPPS. In addition, no association of the viruses with prostate cancer could be found.

Effect of Intravesical Instillations on the Human Complement Factor H Related Protein (BTA stat) Test

Objectives: The BTA stat is a rapid, non–invasive, qualitative urine test that detects bladder tumor–associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test. Methods: 501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty–seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations. Results: The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended. Conclusion: The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.

Long-term Outcome of Patients with Frequently Recurrent Non–muscle-invasive Bladder Carcinoma Treated with One Perioperative Plus Four Weekly Instillations of Mitomycin C Followed by Monthly Bacillus Calmette-Guérin (BCG) or Alternating BCG and Interferon-α2b Instillations: Prospective Randomised FinnBladder-4 Study

BACKGROUND Recurrent TaT1 non-muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. OBJECTIVE To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. DESIGN, SETTING, AND PARTICIPANTS Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. INTERVENTION One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. RESULTS AND LIMITATIONS The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival. CONCLUSIONS Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. PATIENT SUMMARY We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. TRIAL REGISTRATION The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.

Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer : a preplanned safety report of the SPCG-13 trial

Background:Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13).Methods:The inclusion criteria are the following: men >18 and ⩽75 years of age, WHO/ECOG performance status 0–1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8–10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m−2 d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org).Results:In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3–4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3–4 toxicities at 12 weeks after the randomization.Conclusions:Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

Retrospective Analysis of Long-Term Outcomes of 64 Patients Treated by Endopyelotomy in Two Low-Volume Hospitals: Good and Durable Results

BACKGROUND AND PURPOSE Endopyelotomy is an option for the management of ureteropelvic junction (UPJ) obstruction, but long-term outcome data are lacking. The purpose of this study was to evaluate the long-term outcome of endopyelotomy. PATIENTS AND METHODS We retrospectively collected data from all endopyelotomies performed in two low-volume hospitals in Finland between 1987 and 2007. The diagnosis was based primarily on urography results. We also conducted a patient survey during the fall of 2007 for the subjective outcome of the operation. There were 18, 17, and 29 patients with a mean follow-up time 152.2, 67.1, and 77.6 months treated by percutaneous antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. RESULTS Reoperation for recurrent UPJ obstruction was required for 0, 1 (6%) and 5 (17%) of the patients, the radiographic outcome of the operation was better in 17 (94%), 13 (76%), and 18 (62%) of the patients, and 0, 2 (12%), and 5 (17%) of the patients experienced no relief in pain after percutaneous antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. Complications necessitating intervention were recorded for 7 (38.9%), 4 (23.5%), and 4 (13.8%) patients after antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. According to the patient survey, 15 (100%), 11 (73%), and 19 (86%) of the respondents were satisfied with the results of the operation after antegrade endopyelotomy, Acucise endopyelotomy, and retrograde endopyelotomy, respectively. The patients were mainly monitored by radiologic examinations, not by renography. CONCLUSIONS Endopyelotomy offers good and durable results in the long-term. Complications were common, however, and laparoscopic pyeloplasty may be a recommended option for management of primary UPJ obstruction.

Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non–Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study

BACKGROUND Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression. OBJECTIVE We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008. INTERVENTIONS The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models. RESULTS AND LIMITATIONS The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04). CONCLUSIONS The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a. PATIENT SUMMARY A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a. TRIAL REGISTRATION Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.

Reply from Authors re: Robert S. Svatek. Long-term Outcomes of the FinnBladder-4 Study. Eur Urol 2015;68:618–9: Which Type of Maintenance Matters?

with the SWOG-8507 regimen [7] [4_TD