Summary of changes
New relevant references have been identified through a structured assessment of the literature and incorporated in the various chapters of the 2021 EAU MIBC Guidelines resulting in new sections and added and revised recommendations in:
- Section 3.3.3 Guidelines for the assessment of tumour specimens
| Recommendation | Strength rating |
| Record the sampling sites, as well as information on tumour size when providing specimens to the pathologist. | Strong |
- Section 5.1.8 Summary of evidence and guidelines for the primary assessment of presumably invasive bladder tumours
| Summary of evidence | LE |
| In men, prostatic urethral biopsy includes resection from the bladder neck to the verumontanum (between the 5 and 7 o’clock position) using a resection loop. In case any abnormal-looking areas in the prostatic urethra are present at this time, these need to be biopsied as well. | 2b |
| Recommendations | Strength rating |
In men with a negative prostatic urethral biopsy undergoing subsequent orthotopic neobladder construction, an intra-operative frozen section can be omitted. | Strong |
| In men with a prior positive transurethral prostatic biopsy, subsequent orthotopic neobladder construction should not be denied a priori, unless an intra-operative frozen section of the distal urethral stump reveals malignancy at the level of urethral dissection. | Strong |
- Section 5.2.1 - Local staging of MIBC; inclusion of data on multiparametric MRI using the Vesical Imaging Reporting and Data System (VI-RADS) scoring system. No new recommendation has been provided.
- Section 5.3 - MIBC and health status; this section has been updated, introducing the concept of frailty.
- Chapter 6 - Markers; this chapter has been significantly revised, presenting two new recommendations.
6.5 Summary of evidence and recommendations for urothelial markers
| Summary of evidence | LE |
There is insufficient evidence to use TMB, molecular subtypes, immune or other gene expression signatures for the management of patients with urothelial cancer. | - |
| Recommendations | Strength rating |
| Evaluate PD-L1 expression (by immunohistochemistry) to determine the potential for use of pembrolizumab or atezolizumab in previously untreated patients with locally advanced or metastatic urothelial cancer who are unfit for cisplatin-based chemotherapy. | Weak |
| Evaluate for FGFR2/3 genetic alterations for the potential use of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma who have progressed following platinum-containing chemotherapy (including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy). | Weak |
- 2 - Pre- and post-operative radiotherapy in muscle-invasive bladder cancer; this section was revised and new data added, resulting in an additional recommendation.
7.2.3 Summary of evidence and guidelines for pre- and post-operative radiotherapy
| Summary of evidence | LE |
| Addition of adjuvant RT to chemotherapy is associated with an improvement in local relapse free survival following cystectomy for locally advanced bladder cancer (pT3b─4, or node-positive). | 2a |
| Recommendation | Strength rating |
Consider offering adjuvant radiation in addition to chemotherapy following radical cystectomy, based on pathologic risk (pT3b–4, or positive nodes, or positive margins). | Weak |
7.3.10 Summary of evidence and guidelines for radical cystectomy and urinary diversion
| Summary of evidence | LE |
| Ensuring that patients are well informed about the various urinary diversion options prior to making a decision may help prevent or reduce decision regret, independent of the method of diversion selected. | 3 |
- 5.4 Trimodality bladder-preserving treatment
- 7 Metastatic disease: data from a number of key trials has been included, in particular on immunotherapy combinations in first- and later-line setting, resulting in a number of new recommendations and a change to the treatment flowchart (Figure 7.2).
7.7.8 Summary of evidence and guidelines for metastatic disease
| Summary of evidence | LE |
| PD-1 inhibitor pembrolizumab has been approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase III trial. | - |
| PD-L1 inhibitors atezolizumab, nivolumab, durvalumab and avelumab have been FDA approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase II trial. | - |
| PD-1 inhibitor pembrolizumab and PD-L1 inhibitor atezolizumab have been approved for patients with advanced or metastatic UC unfit for cisplatinum-based first-line chemotherapy and with overexpression of PD-L1 based on the results of single-arm phase II trials. | - |
| The combination of chemotherapy plus pembrolizumab or atezolizumab and the combination of durvalumab and tremelimumab have not demonstrated an OS survival benefit compared to platinum-based chemotherapy alone. | - |
| Switch maintenance with the PD-L1 inhibitor avelumab has demonstrated significant OS benefit in patients achieving at least stable disease on first-line platinum-based chemotherapy. | - |
| Recommendations | Strength rating |
| First-line treatment for platinum-fit patients | |
| Use cisplatin-containing combination chemotherapy with GC or HD-MVAC. | Strong |
| In patients unfit for cisplatin but fit for carboplatin use the combination of carboplatin and gemcitabine. | Strong |
| In patients achieving stable disease, or better, after first-line platinum-based chemotherapy use maintenance treatment with PD-L1 inhibitor avelumab. | Strong |
| First-line treatment in patients unfit for platinum-based chemotherapy | |
| Consider checkpoint inhibitors pembrolizumab or atezolizumab. | Weak |
| Second-line treatment | |
| Offer checkpoint inhibitor pembrolizumab to patients progressing during, or after, platinum-based combination chemotherapy for metastatic disease. If this is not possible, offer atezolizumab, nivolumab (EMA, FDA approved); avelumab or durvalumab (FDA approved). | Strong |
| Further treatment after platinum- and immunotherapy | |
Offer treatment in clinical trials testing novel antibody drug conjugates (enfortumab vedotin, sacituzumab govitecan); or in case of patients with FGFR3 alterations, FGFR tyrosine kinase inhibitors. | Strong |
GC = gemcitabine plus cisplatin; FGFR = fibroblast growth factor receptor; HD-MVAC = high-dose intensity
methotrexate, vinblastine, adriamycin plus cisplatin.