This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).
To provide practical evidence-based recommendations and ...consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment.
A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.
Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in “fit” patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/.
This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice.
The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.
Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only.
Patients with treatment-naïve metastatic urothelial carcinoma are grouped according to platinum eligibility based on clear definitions. In general, first-line treatment consists of platinum-based ...chemotherapy in which cisplatin is to be preferred to carboplatin. Patients who are cisplatin ineligible but carboplatin eligible should receive carboplatin-gemcitabine combination chemotherapy. In case of positive programmed death ligand 1 (PD-L1) status, treatment with checkpoint inhibitors (atezolizumab or pembrolizumab) could be an alternative option.
Patients unfit for both cisplatin and carboplatin (platinum unfit) can be considered for immunotherapy (U.S. Food and Drug Administration approved irrespective of PD-L1 status and European Medicines Agency approved only for PD-L1 positive) or can receive best supportive care.
Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution.
This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma.
A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates.
Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations.
This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice.
In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.
Abstract Context Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and ...Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. Objective To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. Evidence acquisition An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. Evidence synthesis Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. Conclusions The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. Patient summary Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.
We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).
To provide practical evidence-based ...recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment.
A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022.
Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ-preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences.
This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice.
The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease.
Purpose We evaluate the ability of an electronic nose to discriminate prostate cancer from benign prostatic hyperplasia using urine headspace, potentially offering a clinically applicable noninvasive ...and rapid diagnostic method. Materials and Methods The ChemPro® 100-eNose was used to discriminate prostate cancer from benign prostatic hyperplasia using urine sample headspace. Its performance was tested with 50 patients with confirmed prostate cancer and 24 samples from 15 patients with benign prostatic hyperplasia (15 patients provided urine preoperatively and 9 patients provided samples 3 months postoperatively) scheduled to undergo robotic assisted laparoscopic radical prostatectomy or transurethral resection of prostate, respectively. The patients provided urine sample preoperatively and those with benign prostatic hyperplasia also provided samples 3 months postoperatively to be used as a pooled control sample population. A discrimination classifier was identified for eNose and subsequently, sensitivity and specificity values were determined. Leave-one-out cross-validation was performed. Results Using leave-one-out cross-validation the eNose reached a sensitivity of 78%, a specificity of 67% and AUC 0.77. Conclusions The electronic nose is capable of rapidly and noninvasively discriminating prostate cancer and benign prostatic hyperplasia using urine headspace in patients undergoing surgery.
In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and ...quality of care.
A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate.
Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool.
After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively.
Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes.
Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided.
Based on this systematic review, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10 and preferably >20 radical cystectomies annually or refer patients to a center that performs this number. Hospital volume is likely associated with lower in-hospital, 30-d, and 90-d mortality as well as more favorable secondary outcomes (complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rates). For surgeon volume, the evidence is less convincing and the main driver of outcomes seems to be the hospital volume. Notwithstanding the evidence limitations, this systematic review includes data of more than 500000 unique patients.
•LC–MS/MS method was developed and validated to analyze polyamines from urine samples.•The method omits the laborious derivatization steps in the sample preparation.•Free, monoacetylated and ...diacetylated polyamines can be analyzed simultaneously.•The method can be used to study polyamine levels in urine of cancer patients.
Polyamines are promising biochemical markers of cancer and many other pathophysiological conditions, and thus their concentrations in biological fluids are a matter of interest. However, since the concentrations of these compounds are low, their quantitation is typically based on methods requiring laborious sample preparation. Here we developed and validated an LC–MS/MS method to analyze simultaneously free (DAP, PUT, CAD, SPD, SPM) monoacetylated (AcPUT, AcCAD, N1AcSPD, N8AcSPD, N1AcSPM) and diacetylated (DiAcPUT, DiAcCAD, DiAcSPD, DiAcSPM) polyamines from human urine without the need for derivatization. Deuterium labeled polyamines were the internal standards for each analyte. Diluted urine samples spiked with internal standards were filtered through a strong anion exchange resin prior to LC–MS/MS analysis. The chromatographic separation of 14 polyamines was achieved in 12min on C18 column with 0.1% HFBA (v/v) as the ion-pairing agent and a water–acetonitrile gradient. Ionization was performed with positive electrospray ionization (ESI) and detection was with a triple quadrupole mass spectrometer with selected reaction monitoring. Calibration curves ranged from up to 5 to 10,000nM. The accuracy and precision of the method were determined using urine based quality control samples, and matrix effects were examined by using standard addition methods. This novel method is suitable for elucidating differences in urinary polyamine excretion in cancer patients and healthy humans.
Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies.
To provide updated practical recommendations for the diagnosis and management of PUC.
A ...systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed.
Urothelial carcinoma of the urethra is the predominant histological type of PUC (54–65%), followed by squamous cell carcinoma (16–22%) and adenocarcinoma (10–16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated.
These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC.
Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.
Primary urethral carcinoma (PUC) is an aggressive disease, requiring appropriate and timely multidisciplinary management. These European Association of Urology guidelines on PUC provide up-to-date information on the diagnosis and management of PUC.
Context
Pelvic organ‐preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical ...cystectomy (RC).
Objective
To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer.
Evidence acquisition
Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single‐arm case series were included. The primary outcomes were sexual function at 6–12 months after surgery and oncological outcomes including disease recurrence and overall survival (OS) at >2 years. Secondary outcomes included urinary continence at 6–12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment.
Evidence synthesis
The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched‐pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients’ sexual satisfaction score of 88.5 (80–100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow‐up of between 12 and 132 months. At 3 and 5 years, cancer‐specific survival was 70–100% and OS was 65–100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night‐time continence rates were 58–100% and 42–100%, respectively. Overall, the self‐catheterisation rate was 9.5–78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup‐analysis, a narrative synthesis approach was used. The overall RoB was high across all studies.
Conclusion
For well‐selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC, oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting.
Variant histology of muscle-invasive (MIBC) and metastatic (mBC) bladder cancer may define the cancer treatment modality and oncological outcomes.
To determine the prognostic effect and impact of ...therapy of urothelial and nonurothelial histological variants on the oncological outcomes of MIBC and mBC.
Medline, Embase, Cochrane controlled trial databases, and ClinicalTrials.gov were systematically searched. Patients with histological variants of MIBC or/and mBC from prospective and retrospective comparative studies and single-arm case series published after the year of 2000 were included. Treatment outcomes (overall, recurrence-free, and disease-specific survival) were extracted and reported. Risk of bias (RoB) assessment was performed using Quality in Prognosis Studies tool.
The search yielded 2450 unique articles, of which 41 articles involving a total of 27 672 patients with histological variants were included. Twenty-eight studies had a comparative study design. Two different study settings were seen: large database studies without centralised pathological review and small series with re-review by uropathologists. Although most of the histological variants show similar oncological outcomes after radical cystectomy (RC), signet ring cell, spindle cell, and neuroendocrine tumours showed inferior survival compared with pure urothelial bladder cancer (PUC). Owing to potential misleading interpretations and reporting as well as large heterogeneity between studies, a narrative synthesis approach instead of subgroup analyses was used. Most studies had a moderate RoB.
The data about prognosis and treatment of the variant histology are still immature and assessed mostly in cystectomy patients. Based on this systematic review, all patients with MIBC should be treated with RC. Neoadjuvant chemotherapy may be beneficial for patients with micropapillary, plasmacytoid, sarcomatoid, and mixed variants, and especially for patients with neuroendocrine tumours. Metastatic bladder cancer should be treated as PUC.
In this report, we looked at the prognosis and treatment of different bladder cancer histologies. We found that outcomes varied with divergent histologies and appropriate treatment should be based on the histological finding.
Selection of treatment for bladder cancer should include assessment of histological findings as treatment outcomes will vary depending on the histological variant identified. Based on this systematic review, with the caveat that not all treatment modalities currently offered to patients with muscle-invasive bladder cancer (MIBC) could be assessed due to lack of data (eg, for bladder-preserving techniques), radical cystectomy should be offered to all patients diagnosed with MIBC. Neoadjuvant chemotherapy may be beneficial for patients with micropapillary, plasmacytoid, sarcomatoid, and mixed variants, and neuroendocrine features. Improved bladder tumour resection techniques, and advanced tissue sampling and reporting will add more evidence about the role of histological variants.
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