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.
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.
Abstract Introduction Different sexual function–preserving surgical techniques aimed at improving voiding and sexual function in patients undergoing radical cystectomy for bladder cancer have been ...described. The objective of this systematic review is to determine the effect of sexual function–preserving cystectomy (SPC) on functional and oncological outcomes. Materials and methods Relevant databases were searched covering the time frame 2000 to 2015. All publications presenting data on any type of SPC reporting oncological or functional outcomes with a minimum follow-up of 1 year were identified. Comparative studies including a minimum of 30 patients and single-arm case series with a minimum of 50 patients were selected. No language restrictions were applied. Results In a total of 8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques. Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%–55.0% in the control group) and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in comparative studies reporting oncological outcomes. Postoperative potency was significantly better in the SPC groups in 6 studies comparing sexual function–preserving cystectomy vs. radical cystectomy ( P <0.05). No major effect on continence was found. Overall, there was moderate to high risk of bias and confounding. Conclusions The evidence base for prostate-, capsule-, or nerve-sparing cystectomy suggests that these procedures may yield better sexual outcomes than standard cystectomy, without compromising oncological outcomes. However, the overall quality of the evidence was moderate, and hence if offered, patients must be carefully selected, counseled, and closely monitored.
A negative biopsy in patients with Prostate Imaging Reporting and Data System/Likert ≥3 lesions causes a frequent clinical conundrum that can be due to a false positive magnetic resonance imaging ...(MRI) finding or a false negative prostate biopsy. In these patients, we suggest MRI re-reading and follow-up with repeat multiparametric MRI or standard repeat biopsy in highest-risk cases.
Multiparametric magnetic resonance imaging (mpMRI) has high sensitivity but low specificity for prostate cancer (PCa) diagnosis. The aim of our systematic review was to investigate the proportion of PCa found at a repeat biopsy in patients with a negative initial prostate biopsy, despite initial positive mpMRI. Included patients had a Prostate Imaging Reporting and Data System (PI-RADS)/Likert 3–5 lesion on mpMRI prior to the initial mpMRI-targeted prostate biopsy, which was negative for PCa on histology. The main outcomes were the overall and clinically significant PCa (csPCa; International Society of Urological Pathology >1 or any provided definition) percentages at a repeat biopsy. Out of 1179 articles identified, nine studies were included (a total of 485 patients). For patients with PI-RADS 3 lesions, overall and csPCa detection percentages ranged from 0% to 80% and from 0% to 20%, respectively, while for patients with PI-RADS ≥4 lesions, the corresponding percentages were 15.4–86% and 7.7–57%. An overall cancer detection percentage of 87.5% was reported in patients with Likert 5 lesions. Limitation of our review is the small number of studies and the protocol revision that allowed studies with <50 patients. In patients with a positive MRI result and a negative initial MRI-targeted biopsy, we suggest MRI re-reading and follow-up with repeat mpMRI or the standard repeat biopsy in cases at the highest risk.
Literature has shown that in men with an abnormal prostate magnetic resonance imaging (MRI) scan but a normal biopsy, a significant prostate cancer can be present. MRI scans should be double checked, followed by standard checkups or repeat prostate biopsy, especially in highly suspicious cases.
Purpose
White light (WL) is the traditional imaging modality for transurethral resection of bladder tumour (TURBT). IMAGE1S is a likely addition. We compare 18-mo recurrence rates following TURBT ...using IMAGE1S versus WL guidance.
Methods
Twelve international centers conducted a single-blinded randomized controlled trial. Patients with primary and recurrent non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by IMAGE1S or WL. Eighteen-month recurrence rates and subanalysis for primary/recurrent and risk groups were planned and compared by chi-square tests and survival analyses.
Results
689 patients were randomized for WL-assisted (
n
= 354) or IMAGE1S-assisted (
n
= 335) TURBT. Of these, 64.7% had a primary tumor, 35.3% a recurrent tumor, and 4.8%, 69.2% and 26.0% a low-, intermediate-, and high-risk tumor, respectively. Overall, 60 and 65 patients, respectively, completed 18-mo follow-up, with recurrence rates of 31.0% and 25.4%, respectively (
p
= 0.199). In patients with primary, low-/intermediate-risk tumors, recurrence rates at 18-mo were significantly higher in the WL group compared with the IMAGE1S group (31.9% and 22.3%, respectively:
p
0.035). Frequency and severity of adverse events were comparable in both treatment groups. Immediate and adjuvant intravesical instillation therapy did not differ between the groups. Potential limitations included lack of uniformity of surgical resection, central pathology review, and missing data.
Conclusion
There was not difference in the overall recurrence rates between IMAGE1S and WL assistance 18-mo after TURBT in patients with NMIBC. However, IMAGE1S-assisted TURBT considerably reduced the likelihood of disease recurrence in primary, low/intermediate risk patients.
Registration
ClinicalTrials.gov Identifier NCT02252549 (30-09-2014).
Purpose The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer ...specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. Materials and Methods We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. Results Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.
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.
To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus.
The ...records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates.
LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN−) disease was documented in 573 patients, 447 of them underwent LND with 43 cN− patients (9.6%) revealing positive LNs at pathology. LN positive cN− patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015).
The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting.
•RCC patients with tumor thrombus are pT3 by definition; they are at high-risk.•Analysis of the largest multi-institutional RCC tumor thrombus database (IRCC-VTC).•9.6% of clinically node-negative patients were pathologically node-positive.•cN0/pN1 had better CSS when compared to cN1/pN1.
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