Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin compared with intravesical mitomycin in patients with non-muscle-invasive bladder cancer: results from a prospective randomized phase III trial.

Contains fulltext : 108422.pdf (publisher's version ) (Open Access)PURPOSE: Despite current treatment after transurethral resection of a bladder tumor, recurrences and progression remain a problem. Keyhole limpet hemocyanin (KLH) was beneficial in earlier studies. In this study, safety and efficacy of KLH were compared with that of mitomycin (MM). PATIENTS AND METHODS: Patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ were enrolled in a randomized phase III trial. In all, 283 patients were randomly assigned for 16 adjuvant intravesical instillations with KLH after preimmunization, and 270 patients were randomly assigned for 11 adjuvant intravesical instillations with MM. Primary outcome measurement was recurrence-free survival (RFS). Secondary outcome measurements were progression-free survival, adverse events (AEs), and the effect of delayed-type hypersensitivity (DTH) response on clinical outcome. RESULTS: There were significantly more pT1 tumors in the MM group (P = .01). In a log-rank test, univariate and multivariate Cox regression analysis, KLH was less effective than MM regarding RFS (all P < .001). Progression was uncommon (n = 20). In univariate Cox regression analyses, KLH tended to prevent progression more effectively than MM, but in multivariate Cox regression analyses, this could not be shown. AEs were common but mild. Fever, flu-like symptoms, and fatigue occurred significantly more after KLH treatment. Allergic reactions and other skin disorders occurred significantly more after MM treatment. Significantly more DTH-positive patients developed a recurrence than DTH-negative patients. CONCLUSION: KLH had a different safety profile and was inferior to MM in preventing NMIBC recurrences. KLH tended to be more effective than MM in preventing progression. More research is needed to clarify the immunologic effects of KLH and the effects of KLH on progression

Quality of life with pharmacological treatment in patients with benign prostatic enlargement: results from the Evolution European Prospective Multicenter Multi-National Registry Study.

Item does not contain fulltext Background Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures. Methods Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index. Results The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0-26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients. Conclusions After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial

Background: A survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT). Objective: To determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa. Design, setting, and participants: The HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014. Intervention: Patients were randomised to ADT with EBRT or to ADT alone. Outcome measurements and statistical analysis: Patients completed two validated HRQoL questionnaires (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core Module (QLQ-C30) and EORTC Quality of Life Questionnaire Prostate Module [QLQ-PR25]) at baseline and at 3, 6, 12, and24 mo after the initiation of treatment. The effect of both treatments was evaluated based on mixed-effect models. Results and limitations: Patient characteristics and HRQoL scores at baseline were similar in both arms. At baseline, 98% of patients completed the questionnaires, compared with 58% at 24 mo. Patients reported significantly more diarrhoea (difference between the groups 10.8; 95% confidence interval [CI] 7.3–14.2), bowel symptoms (4.5; 95% CI 2.1–6.8), and urinary symptoms (11.9; 95% CI 8.9–14.8) after EBRT and ADT compared with ADT alone (all between-arm difference p < 0.001). Urinary complaints levelled at 6 mo. At 2 yr, only bowel symptom scores were significantly different (8.0; 95% CI 4.8–11.1, p ≤ 0.001), but 68% of patients in the radiotherapy group did not report clinically relevant worsening of their bowel symptom scores. Conclusions: Patients with bone mPCa reported temporary modest urinary and bowel symptoms after combined treatment with EBRT of the prostate and ADT compared with ADT alone. For some patients (22%), deterioration of bowel functions remains at 2 yr, whereas general HRQoL does not deteriorate. Patient summary: This study investigated the effect of radiotherapy to the prostate added to hormonal therapy on patient-reported health-related quality of life (HRQoL) in patients with primary bone metastatic prostate cancer. Most patients reported only temporary urinary and bowel symptoms. In 22% of patients, bowel symptoms remained at 2 yr, whereas general HRQoL did not deteriorate. Patients with bone metastatic prostate cancer reported temporary modest urinary and bowel symptoms after combined treatment with prostate radiotherapy and hormonal therapy compared with hormonal therapy alone. Both treatments did not affect global health-related quality of life

Quality of Life in Patients with High-grade Non–muscle-invasive Bladder Cancer Undergoing Standard Versus Reduced Frequency of Bacillus Calmette-Guérin Instillations: The EAU-RF NIMBUS Trial

Background: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non–muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. Objective: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. Design, setting, and participants: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. Outcome measurements and statistical analysis: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. Results and limitations: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. Conclusions: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. Patient summary: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non–muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non–muscle-invasive bladder cancer

Treatment of High-grade Non–muscle-invasive Bladder Carcinoma by Standard Number and Dose of BCG Instillations Versus Reduced Number and Standard Dose of BCG Instillations: Results of the European Association of Urology Research Foundation Randomised Phase III Clinical Trial “NIMBUS”

Background: Intravesical instillation of bacillus Calmette-Guérin (BCG) is an accepted strategy to prevent recurrence of non–muscle-invasive bladder cancer (NMIBC) but associated with significant toxicity. Objective: NIMBUS assessed whether a reduced number of standard-dose BCG instillations are noninferior to the standard number and dose in patients with high-grade NMIBC. Design, setting, and participants: A total of 345 patients from 51 sites were randomised between December 2013 and July 2019. We report results after a data review and safety analysis by the Independent Data Monitoring Committee based on the cut-off date of July 1, 2019. Intervention: The standard BCG schedule was 6 wk of induction followed by 3 wk of maintenance at 3, 6, and 12 mo (15 instillations). The reduced frequency BCG schedule was induction at wks 1, 2, and 6 followed by 2 wk (wks 1 and 3) of maintenance at 3, 6, and 12 mo (nine instillations). Outcome measurements and statistical analysis: The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity. Results and limitations: In total, 170 patients were randomised to reduced frequency and 175 to standard BCG. Prognostic factors at initial resection were as follows: Ta/T1: 46/54%; primary/recurrent: 92/8%; single/multiple: 57/43%; and concomitant carcinoma in situ: 27%. After 12 mo of median follow-up, the intention-to-treat analysis showed a safety-relevant difference in recurrences between treatment arms: 46/170 (reduced frequency) versus 21/175 patients (standard). Additional safety analyses showed a hazard ratio of 0.40 with the upper part of the one-sided 97.5% confidence interval of 0.68, meeting a predefined stopping criterion for inferiority. Conclusions: The reduced frequency schedule was inferior to the standard schedule regarding the time to first recurrence. Further recruitment of patients was stopped immediately to avoid harm in the reduced frequency BCG arm. Patient summary: After surgical removal of the tumour, patients with high-grade non–muscle-invasive bladder cancer are treated with bacillus Calmette-Guérin to prevent recurrence and progression. This is associated with significant side effects. We report the results of a clinical trial showing a reduction in the number of instillations (from 15 to nine in total) being inferior to the standard protocol. From today's perspective, complete tumour resection and a standard number of instillations remain the standard of care

Therapies used in prostate cancer patients by European urologists: data on indication with a focus on expectations, perceived barriers and guideline compliance related to the use of bisphosphonates.

Item does not contain fulltextIntroduction: The aim of our survey was to evaluate the usage and indications of various metastatic prostate cancer (PCa) therapies, and to identify barriers to usage of bisphosphonates (BPs). Materials and Methods: Between March and June 2009, an internet-based survey was performed among board-certified urologists of the EAU who treated >/=10 patients with metastatic PCa annually. Results: Questionnaires completed by 200 urologists from 12 European countries including 27,442 PCa patients were used for analyses. On average, 22% of the patients presented in stage IV, 15% had bone metastases and 10% received BPs. In most countries, BPs were used to the same extent in hormone-naive and castration-resistant PCa (CRPC). A total of 23% of urologists prescribed chemotherapy in patients with hormone-sensitive PCa, and 55% of the urologists did not administer androgen deprivation maintenance therapy in patients with CRPC. Conclusions: BPs were frequently used in PCa with bone metastases, although current guidelines recommend their use only in CRPC. Standardized multidisciplinary educational programs should be developed in order to prevent non-indicated early chemotherapy in hormone-sensitive patients and to stimulate maintenance of androgen deprivation therapy in CRPC patients. Also, programs facilitating home infusions for patients who need intravenous BPs are needed in specific countries to optimize treatment of CRPC