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Purpose: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy–effectiveness gap). The purpose of this study was to evaluate the efficacy–effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. Methods: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). Results: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9–13.0], which was shorter compared to clinical trial findings (range mOS: 12.7–14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5–11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55–1.47], P-value = 0.674). Conclusion: There seems to be an efficacy–effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld., Patients and Methods: The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%)., Results: A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48)., Conclusion: The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC., Trial Registration: Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954., Competing Interests: Diclosure JWMM and SS report a research agreement with Menarini, unrelated to the currently submitted manuscript. JLB reports consultancy work for MSD, Janssen, ISMAR Health Care, Eight Medical, BMS and AMBU (all paid to the Erasmus MC) and a research agreement with Decipher. All other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited., Objective: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice., Methods and Materials: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status., Results: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage., Conclusion: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although urinary adverse events after treatment of prostate cancer (CaP) are common, population-based studies on functional outcomes are scarce. The aim of this study is to evaluate the occurrence of urinary incontinence (UI) and erectile dysfunction (ED) in daily clinical practice using a nationwide Dutch cohort of patients with localized or locally advanced CaP., Basic Procedures: Patients were invited to complete the EPIC-26 questionnaire before treatment (baseline) and at 12 and 24 months after diagnosis. We calculated the mean EPIC-26 domain scores, stratified by treatment modality (i.e., radical prostatectomy, external radiotherapy, and no active treatment), and the proportions of patients with UI (defined as ≥ 2 pads per day) and ED (defined as erections not firm enough for sexual intercourse). Logistic regression modeling was used to explore the factors related to UI and ED after surgery., Main Findings: In total 1,759 patients participated in this study. Patients undergoing radical prostatectomy experienced clinically relevant worsening in the urinary incontinence domain. After excluding patients who reported UI at baseline, 15% of patients with prostatectomy reported UI 24 months after diagnosis. Only comorbidity was associated with UI in surgically treated patients. Regardless of treatment, patients reported a clinically significant reduced sexual functioning over time. Before treatment, 54% of patients reported ED. Among the 46% remaining patients, 87% of patients treated with radical prostatectomy reported ED 24 months after diagnosis, 41% after radiotherapy, and 46% in patients without active treatment. Bilateral nerve-sparing surgery was the only factor associated with ED after 24 months., Principal Conclusions: UI and ED frequently occur in patients with localized and locally advanced CaP, in particular after radical prostatectomy. The higher occurrence rate of UI and ED, compared with clinical trial participants, supports the importance of real-world data, which can be used for local treatment recommendations and patient information, but also to evaluate effects of future initiatives, such as treatment centralization and research aimed at improving functional outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Complications after intravesicalMycobacterium bovisBCG instillation Intravesical instillation of Mycobacterium bovis BCG is frequently used for non-muscle invasive high-grade urothelial cell carcinoma of the bladder. M. bovisBCG is a mycobacterium and was one of the first cancer immunotherapies. It activates the immune system and so reduces disease recurrence. Although rare, this treatment can lead to mycobacterial infections or systemic immune reactions. Diagnosing these complications is often challenging because the symptoms are non-specific. In addition, M. bovisBCG infections are hard to detect with current diagnostics, i.e. bacterial cultures, PCR and radiological imaging. Thus, proper treatment is often delayed as M. bovis does not respond to conventional broad-spectrum antibiotics. In this article we present three patients with BCG pneumonia, BCG arthritis and BCG cystitis, respectively. Subsequently, we describe the history of M. bovis BCG, its pathophysiology, the clinical presentation of its complications and diagnostics and treatment.

Objective: To determine the effect of radical prostatectomy (RP) hospital volume on the probability of post-RP incontinence., Design: Retrospective research based on claims-based data of health insurers., Method: For every patient with RP the probability of incontinence was determined, based on the definition of claims of one or more incontinence pads per day. Casemix corrections were made based on indicators available in claims-data: age, lymph node dissection, and radiotherapy. No casemix corrections could be made for tumour stage and surgical technique., Results: A total of 1590 patients were included in this study; for 26.0% of these patients, an average of one or more incontinence pads per day were claimed for. A significant relation between the volume of RP per hospital and the claims of incontinence material was observed. The probability of incontinence was significantly lower in hospitals with a volume of more than 100 RP patients per year when compared to hospitals with less than 100 RP patients per year., Conclusion: The probability of post-RP incontinence decreases as hospitals conduct more RP procedures. The casemix factors included in the analysis only had a limited impact on this observation.