Search

Item does not contain fulltext PURPOSE: In the Netherlands yearly more than 5000 patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). With a specificity of 88.0% and a negative predictive value (NPV) for high grade NMIBC of 99.3%, the Bladder EpiCheck (BE) urine test may be used in NMIBC to reduce the burden of follow-up cystoscopies. METHODS: In this study a cost analysis of the BE follow-up strategy in the Dutch healthcare system was performed. In half of the follow-up appointments, BE was used as a rule-in for cystoscopy. In addition, the possible delay in recurrence detection was estimated. A cost calculation tool was developed using Microsoft Excel. RESULTS: The BE strategy results in an estimated cost reduction of 8%, 4% and 9% in low, intermediate and high risk patients, respectively. In the Netherlands this may result in a cost reduction of approximately 1.6 million euro per year. The estimated delay in the detection of recurrent disease would be 3.9, 1.7 and 1.3 months in low, intermediate and high risk NMIBC patients respectively. CONCLUSION: To conclude, the BE can be used to reduce the costs of NMIBC follow-up, with a small delay in diagnosis of recurrent disease. 01 februari 2023

Purpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). Methods Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995–December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017–October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with y)pT2N0 vs. y)pT2N+ disease was estimated by the Kaplan–Meier method. Results In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with y)pT2N+ and y)pT2N0, median OS was 3.5 years (95% CI 2.5–8.9) versus 12.9 years (95% CI 11.7–14.0), respectively. Conclusion Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

Aim Optimal management of bladder cancer requires an accurate, standardised and timely pathological diagnosis, and close communication between surgeons and pathologists. Here, we provide an update on pathology reporting standards of transurethral resections of the bladder and cystectomies. Methods We reviewed recent literature, focusing on developments between 2013 and 2021. Results Published reporting standards developed by pathology organizations have improved diagnosis and treatment. Tumor sub-staging and subtyping has gained increased attention. Lymph nodes continue to be an area of debate, and their staging has seen minor modifications. Several tasks, particularly regarding specimen preparation (“grossing”), are not yet standardized and offer opportunity for improvement. Molecular classification is rapidly evolving, but currently has only limited impact on management. Conclusion Pathological reporting of bladder cancer is continuously evolving and remains challenging in some areas. This review provides an overview of recent major developments, with a particular focus on published reporting standards.

Contains fulltext : 244232.pdf (Publisher’s version ) (Open Access) Patients with non-muscle invasive bladder cancer (NMIBC) have high recurrence and progression rates in spite of tumor resection and adjuvant instillation therapy. To detect recurrences and progression, these patients remain under frequent follow-up. Follow-up, however, is not well defined. Frequency and duration of follow recommendations are based on low levels of evidence, which is illustrated by clear differences in these recommendations per guideline, even when specified per risk group. Additionally, follow-up is recommended with cystoscopy and cytology in selected patients, which both have clear limitations. Fact is that follow-up in NMIBC is too frequent, with low levels of evidence and suboptimal tools, and it is patient unfriendly and costly. Improved cystoscopy techniques are unproven or impractical in the outpatient follow-up setting. Urinary markers have been around for decades, but never widely used in clinical practice. New (epi)genetic markers, however, could play a significant role in future follow-up of NMIBC. They have been shown to have very high negative predictive values for recurrences in follow-up of NMIBC, especially high-grade recurrences. Several studies suggested that these markers could be used to adapt follow-up cystoscopy frequency. What still needs study and confirmation is the cost-effectiveness of the use of these markers, which is highly dependent on health care costs per country and marker price. In all, however, implementation of these new urinary markers after confirmation of current results might significantly reduce patient burden and health care costs in the near future without reducing quality.

Purpose Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. Methods In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. Results In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p = 0.0009), miR-92b (− 3.1 fold; p p p = 0.0006) and miR-4417 (5.0-fold; p = 0.0005) were most upregulated. While KLK3, miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. Conclusion We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.

Item does not contain fulltext PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Purpose To compare clinically significant prostate cancer (csPCa) detection rates between magnetic resonance imaging (MRI)–transrectal ultrasound (TRUS) fusion-guided prostate biopsy (FGB) and direct in-bore MRI-guided biopsy (MRGB). Methods We performed a comparison of csPCa detection rates between FGB and MRGB. Included patients had (1) at least one prior negative TRUS biopsy; (2) a Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesion and (3) a lesion size of ≥8 mm measured in at least one direction. We considered a Gleason score ≥7 being csPCa. Descriptive statistics with 95% confidence intervals (CI) were used to determine any differences. Results We included 51 patients with FGB (59 PI-RADS 4 and 41% PI-RADS 5) and 227 patients with MRGB (34 PI-RADS 4 and 66% PI-RADS 5). Included patients had a median age of 69 years (IQR, 65–72) and a median PSA level of 11.0 ng/ml (IQR, 7.4–15.1) and a median age of 67 years (IQR, 61–70), the median PSA 12.8 ng/ml (IQR, 9.1–19.0) within the FGB and the MRGB group, respectively. Detection rates of csPCA did not differ significantly between FGB and MRGB, 49 vs. 61%, respectively. Conclusion We did not detect significant differences between FGB and MRGB in the detection of csPCa. The differences in detection ratios between both biopsy techniques are narrow with an increasing lesion size. This study warrants further studies to optimize selection of best biopsy modality.

Purpose Pre-conditioning of a cell seeded construct may improve the functional outcome of a tissue engineered construct for augmentation cystoplasty. The precise effects of mechanical stimulation on urinary bladder cells in vitro are not clear. In this study we investigate the effect of a cyclic uniaxial strain culture on urinary bladder cells which were seeded on a type I collagen scaffold. Methods Isolated porcine smooth muscle cells or urothelial cells were seeded on a type I collagen scaffolds and cultured under static and dynamic conditions. A uniform cyclic uniaxial strain was applied to the seeded scaffold using a Bose Electroforce Bio-Dynamic bioreactor. Cell proliferation rate and phenotype were investigated, including SEM analysis, RT-PCR and immunohistochemistry for α-Smooth muscle actin, calponin-1, desmin and RCK103 expression to determine the effects of mechanical stimulation on both cell types. Results Dynamic stimulation of smooth muscle cell seeded constructs resulted in cell alignment and enhanced proliferation rate. Additionally, expression of α-Smooth muscle actin and calponin-1 was increased suggesting differentiation of smooth muscle cells to a more mature phenotype. Conclusions Mechanical stimuli did not enhance the proliferation and differentiation of urothelial cells. Mechanical stimulation, i.e., preconditioning may improve the functional in vivo outcome of smooth muscle cell seeded constructs for flexible organs such as the bladder. Electronic supplementary material The online version of this article (doi:10.1007/s00345-017-2013-9) contains supplementary material, which is available to authorized users.

Contains fulltext : 174147.pdf (Publisher’s version ) (Open Access) PURPOSE: To correlate treatment effects of MRI-guided focal laser ablation in patients with prostate cancer with imaging using prostatectomy as standard of reference. METHODS: This phase I study was approved by the Institutional Review Board. Three weeks prior to prostatectomy, five patients with histopathologically proven, low/intermediate grade prostate cancer underwent transrectal MRI-guided focal laser ablation. Per patient, only one ablation was performed to investigate the effect of ablation on the tissue rather than the effectiveness of ablation. Ablation was continuously monitored with real-time MR temperature mapping, and damage-estimation maps were computed. A post-ablation high-resolution T1-weighted contrast-enhanced sequence was acquired. Ablation volumes were contoured and measured on histopathology specimens (with a shrinkage factor of 1.15), T1-weighted contrast-enhanced images, and damage-estimation maps, and were compared. RESULTS: A significant volume correlation was seen between the ablation zone on T1-weighted contrast-enhanced images and the whole-mount histopathology section (r = 0.94, p = 0.018). The damage-estimation maps and histopathology specimen showed a correlation of r = 0.33 (p = 0.583). On histopathology, the homogeneous necrotic area was surrounded by a reactive transition zone (1-5 mm) zone, showing neovascularisation, and an increased mitotic index, indicating increased tumor activity. CONCLUSIONS: The actual ablation zone was better indicated by T1-weighted contrast-enhanced than by damage-estimation maps. Histopathology results highlight the importance of complete tumor ablation with a safety margin.

Item does not contain fulltext OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex((R))-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.

Purpose To develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients. Methods Data from three Dutch trials were combined. Patients treated with intravesical chemotherapy with characteristics according to the IR definition of the EAU guideline 2013 were included. Uni- and multivariable Cox regression with selection methods were used to identify predictors of recurrence at 1, 2, and 5 years. An easy-readable table for recurrence probabilities was developed. An external validation was done using data from Spanish patients. Results A total of 724 patients were available for analyses, of which 305 were primary patients. Recurrences occurred in 413 patients (57 %). History of recurrences, history of intravesical treatment, grade 2, multiple tumors, and adjuvant treatment with epirubicin were relevant predictors for recurrence-free survival with hazard ratios of 1.48, 1.38, 1.22, 1.56, and 1.27, respectively. A table for recurrence probabilities was developed using these five predictors. Based on the probability of recurrence, three risk groups were identified. Patients in each of the separate risk groups should be scheduled for less or more aggressive treatment. The model showed sufficient discrimination and good predictive accuracy. External validation showed good validity. Conclusion In our model, we identified five relevant predictors for recurrence-free survival in IR-NMIBC patients treated with intravesical chemotherapy. These recurrence predictors allow the urologists to stratify patients in risk groups for recurrence that could help in deciding for an individualized treatment approach. Electronic supplementary material The online version of this article (doi:10.1007/s00345-015-1598-0) contains supplementary material, which is available to authorized users.

Item does not contain fulltext PURPOSE: To determine the oncologic benefit or otherwise of local treatment of the prostate in patients with primary metastatic prostate cancer. METHODS: A review of the literature was performed in April 2014 using the Medline/PubMed database. Studies were identified using the search terms "prostate cancer," "metastatic," "metastasis," "high risk," "radiation therapy," "radiotherapy" and "prostatectomy" from 1990 until April, 2014. Articles were also identified through searches of references of these articles. RESULTS: Retrospective series and population-based data suggest that the use of local treatment of the prostate in patients with primary metastatic prostate cancer may improve cancer-specific survival and overall survival compared with treating these patients with androgen deprivation therapy alone. The clinical outcome in metastatic prostate cancer is largely determined by the extent of lymph node involvement and overall metastatic burden. Contemporary data are lacking to recommend one alternative of local therapy (radiotherapy or radical prostatectomy) over the other. The primary limitation of this literature review is the lack of published randomized trial assessing the role of local treatment in addition to systemic therapy. CONCLUSIONS: Local treatment appears to improve oncologic outcomes in metastatic prostate cancer patients. Nevertheless, due to the lack of high-quality evidence, its role needs to be confirmed in future prospective trials. The selection of ideal candidates and optimal treatment alternative (radiotherapy, radical prostatectomy or other) warrants further investigation.