Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.

Sacral Neuromodulation with the InterStim™ System for Intractable Lower Urinary Tract Dysfunctions (SOUNDS): Results of Clinical Effectiveness, Quality of Life, Patient-Reported Outcomes and Safety in a French Multicenter Observational Study.

BACKGROUND: Real-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest. OBJECTIVE: To evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0±3.8 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Voids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p<0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p<0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p<0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p<0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo. CONCLUSIONS: Through a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients. PATIENT SUMMARY: These analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186041.

Comparative study of urodynamic tests after AMS 800 and ZSI 375 insertion.

STUDY DESIGN: Retrospective, non-randomised, single-centre study. OBJECTIVES: Comparative study of urodynamic tests in patients presenting social continence after AMS 800 or ZSI 375 insertion. MATERIALS AND METHODS: Study was open to patients with social continence, implanted with AMS 800 or ZSI 375. Vesical pressure (VP), urethral functional length (FL), maximal urethral pressure (MUP), maximal urethral closure pressure (MUCP), maximal urinary flow rate (Qmax) were registered with standard urodynamic equipment. RESULTS: From March 2012 to September 2014, 27 male patients with AMS 800 and 28 with ZSI 375 were recruited. In the AMS 800 group mean VP was 25.03 cmH2O (range 13-47), mean FL 31.96 mm (range 20-52), mean MUCP 88.29 cmH2O (range 32-160), mean MUP 119.55 cmH2O (range 77-180), mean Qmax 22.86 mL/s (range 5.6-54.6). In the ZSI 375 group, mean VP was 24.89 cmH2O (range 6-40), mean FL 30.53 mm (range 12-87), mean MUCP 70.11 cmH2O (range 38-108), mean MUP 99.89 cm H2O (range 63-134), and mean Qmax 19.25 mL/s range (7.3-39.6). DISCUSSION: Results of urodynamic tests are similar for both artificial urinary sphincters. AMS 800 cuff pressure over 70 cmH2O could be explained by the pelvis pressure and the difference of altitude between the pressure-regulating balloon (PRB) and the cuff. ZSI 375 pressure-regulating tank (PRT) is not influenced by these factors. Very high MUP could be explained with too tightened cuffs. CONCLUSIONS: AMS 800 and ZSI 375 urodynamic tests are similar. Pressure of the pelvis and difference of altitude between the AMS balloon and the cuff can lead to high MUP.

Prostate cancer: what about reproducibility of decision made at multidisciplinary team management?

PURPOSE: The prostate cancer (PCa) treatment is multimodal. Thus multidisciplinary team management (MDTM) decision-making process appears as a tool to answer all aspects of PCa treatment. Our aim was to evaluate the reproducibility of therapeutic decisions made at MDTM. MATERIALS AND METHODS: We compared therapeutic decisions of PCa by presenting the same file of patient under a fake identity after 6 to 12 months from the first presentation. Forty-nine files of radical prostatectomy (RP) (28 pT2, 21 pT3) performed for clinical localized PCa were represented at MDTM which included urologist, oncologist, pathologist and radiologist. Analysis of therapeutic decisions comprised criteria such as: TNM stage, Gleason score, margin status and comorbidities. The reproducibility was assessed statistically by Kappa coefficient. RESULTS: Study subjects included 49 patients who underwent radical prostatectomy (RP). The mean age was similar in pT2 and pT3 groups (P = .09). The mean serum PSA value was 8.32 ng/mL (range, 3.56-19.5) in pT2 group and 9.4 ng/mL (range, 3.8-22) in pT3 group. The margin status in pT2 and pT3 groups was positive in 25.0% and 47.6%, respectively. The decisions made at first and second MDTM for pT2 group were the same in 100% of cases with a perfect kappa coefficient (k = 1). In the group of pT3 (n = 21), the decisions were different in 33% at the second MDTM in comparison to the first MDTM. Especially for pT3b only 29% were reproducible decision with a slight agreement (k = 0.1). Concerning pT3a, 86% of the decisions were reproducible with a substantial agreement (k = 0.74). CONCLUSION: We showed a reliability and reproducibility of decision made at MDTM when guidelines are well defined. The therapeutic attitudes were less reproducible in locally advanced PCa but decision concerning those cases should be made in the setting of guidelines.

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

PURPOSE: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). METHODS: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. RESULTS: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). CONCLUSIONS: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy.

PURPOSE: We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS: We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS: At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS: Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

Erectile function and sexual satisfaction before and after penile prosthesis implantation in radical prostatectomy patients: a comparison with patients with vasculogenic erectile dysfunction.

INTRODUCTION: Patients with erectile dysfunction (ED) after radical prostatectomy (RP) may benefit from penile prosthesis (PP) implantation after failure of less invasive treatments. Aim. To assess surgical outcomes and satisfaction after PP implantation in RP patients and compare the results with those in patients with vasculogenic ED (controls). METHODS: A database of 415 consecutive PPs (January 1996-December 2008) was used to collate data on preimplantation ED treatments, surgical complications, satisfaction, and International Index of Erectile Function (IIEF) scores before and 3 months after implantation. The results for 90 post-RP implants (79 primary, 11 secondary) and 131 implants for vasculogenic ED were compared. MAIN OUTCOME MEASURES: The main outcome measures of this study are intra- and postoperative complications and IIEF domain scores. RESULTS: Mean follow-up of RP patients was 37.6 ± 26.8 months. Mean interval between RP and PP implantation was 31.5 ± 28.7 months. Nearly all primary implants (96.2%) were inflatable (3-piece, 70.1%; 2-piece, 24.1%). There was no significant difference between groups in terms of rates of infection (1.1%), mechanical failure (3.3%), and other surgical complications requiring revision surgery (migration, auto-inflation) (4.4%). For primary implants, the mean preimplantation IIEF score (all items) was significantly lower in RP patients than in controls (14.7 ± 5.9 vs. 22.6 ± 10.8, P = 0.003), chiefly because of significantly lower scores for erectile function, intercourse satisfaction, and orgasmic function. After PP implantation in RP patients, the scores for all domains improved, but the total score remained significantly lower than in controls (63.1 ± 7.0 vs. 68.5 ± 6.9, P = 0.005). The orgasmic function score was significantly lower (P < 0.001). Overall satisfaction rate was 86.1% in RP patients and 90.7% in controls (P = 0.3). CONCLUSIONS: PP implantation after RP is associated with low morbidity and high satisfaction. It improves the scores for all IIEF domains and, in particular, erectile function. Fibrosis of the retropubic space may require a second incision for reservoir placement or implantation of a 2-piece PP.

Six years' experience with high-intensity focused ultrasonography for prostate cancer: oncological outcomes using the new 'Stuttgart' definition for biochemical failure.

OBJECTIVE: • To determine oncological outcomes after high-intensity focused ultrasonography (HIFU) treatment in patients with localized prostate cancer using a new, more accurate, definition ('Stuttgart' definition) of biochemical failure. PATIENTS AND METHODS: • We performed a retrospective review of all patients in our centre who received first-line treatment with a second-generation Ablatherm™ device (EDAP-TMS, Lyon, France). • Oncological failure was given either by biochemical failure (prostate-specific antigen, PSA, nadir plus 1.2 g/mL) (Stuttgart definition) or the start of salvage therapy because of a persistently positive biopsy after the HIFU procedure. • The 5-year biochemical-free survival rate and 5-year disease-free survival rate were calculated. RESULTS: • In total, 53 patients were included (mean age, 72.5 ± 4.5 years, range 60-79 years; 28 low risk and 25 intermediate risk). None had undergone previous hormonal therapy. Mean ±sd follow-up was 45.4 ± 15.5 months (range 16-71 years). Mean (range) pre-treatment PSA was 8.5 ± 4 (0.29-18) ng/mL. The median (range) PSA nadir value was 1 (0.01-14) ng/mL and occurred after a mean (range) of 5.09 (3-24) months. • Overall, 36 patients (67.9%) experienced oncological failure. • These included 33 cases (62.2%) of biochemical failure. A PSA nadir of ≤0.2, 0.21-1.0 and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively. • The 5-year biochemical-free survival rate and disease-free survival rate were 21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL was significantly associated with a risk of biochemical and oncological failure (P= 0.002 and P < 0.001). • Oncological failure was not associated with any risk group. • No patient died from prostate cancer. CONCLUSIONS: • In our experience, Ablatherm™ treatment for clinically localized prostate cancer was associated with a high rate of biochemical failure as determined by the 'Stuttgart' definition, and did not achieve effective cancer control. • The PSA nadir value after HIFU treatment was a significant predictor of treatment failure.