New relevant references have been identified through a structured assessment of the literature and incorporated in the various chapters of the 2019 EAU MIBC Guidelines.
Key changes in the 2019 print are:
- Section 6.3 Prognostic markers – this section was revised, to include new data. Based on the current data, no recommendation can be provided.
- Figures 7.1: Flow chart for the management of T2-T4a N0M0 urothelial BC was adapted.
- Section 7.2 Neoadjuvant therapy – this section was revised and restructured. A new recommendation was added.
7.2.4 Summary of evidence and guidelines for neoadjuvant therapy
| Summary of evidence | LE |
| Currently immunotherapy with checkpoint inhibitors is tested in phase II and III trials. First results are promising. |
| Recommendation | Strength rating |
| Only offer neoadjuvant immunotherapy to patients within a clinical trial setting. | Strong |
- New Section 7.4.7 – Impact of hospital and surgeon volume on treatment outcomes, has been included.
This section is based on the findings of a systematic review (SR) on ‘The impact of the annual hospital and surgeon radical cystectomy volume for BC on peri-operative outcomes and long-term oncological outcomes’ [5];
- Section 7.6.2 External beam radiotherapy (EBRT) - this section was revised, to include new data. The recommendations did not change.
- Section 7.6.4 Multimodality bladder-preserving treatment - this section was revised, to include new data. The recommendations did not change.
- Section 7.7 Adjuvant therapy - this section was revised, to include new data. A new recommendation was included.
7.7.3 Guideline for adjuvant therapy
| Recommendation | Strength rating |
| Offer immunotherapy with a checkpoint inhibitor only in a clinical trial setting. | Strong |
- Section 7.8 Metastatic disease – this section was revised, to include new data, resulting in changes to both the Summary of evidence and the recommendations.
7.8.11 Summary of evidence and guidelines for metastatic disease
| Summary of evidence | LE |
| Post-chemotherapy surgery after partial or complete response may contribute to long-term disease-free survival in selected patients. | 3 |
| PD-1 inhibitor pembrolizumab has been approved for patients with advanced or metastatic urothelial cancer ineligible for cisplatin-based first-line chemotherapy based on the results of a phase II trial but use of pembrolizumab is restricted to PD-L1 positive patients. | 2a
|
| PD-L1 inhibitor atezolizumab has been approved for patients with advanced or metastatic urothelial cancer ineligible for cisplatin-based first-line chemotherapy based on the results of a phase II trial but use of atezolizumab is restricted to PD-L1 positive patients. | 2a
|
| Recommendations | Strength rating |
| First-line treatment for cisplatin-eligible patients | |
| Use cisplatin-containing combination chemotherapy with GC, MVAC, preferably with G-CSF, HD-MVAC with G-CSF or PCG. | Strong |
| Do not offer carboplatin and non-platinum combination chemotherapy. | Strong |
| First-line treatment in patients ineligible (unfit) for cisplatin | |
| Offer checkpoint inhibitors pembrolizumab or atezolizumab depending on PDL-1 status. | Strong |
| Offer carboplatin combination chemotherapy if PD-L1 is negative. | Weak |
| Second-line treatment | |
| Offer checkpoint inhibitor (pembrolizumab) to patients progressing during or after platinum-based combination chemotherapy for metastatic disease. Alternatively, offer treatment within a clinical trial setting. | Strong
|
| Offer zoledronic acid or denosumab for supportive treatment in case of bone metastases. | Weak |
| Only offer vinflunine to patients for metastatic disease as second-line treatment if immunotherapy or combination chemotherapy is not feasible. Alternatively, offer vinflunine as third- or subsequent treatment line. | Weak
|
GC = gemcitabine plus cisplatin; G-CSF = granulocyte colony-stimulating factor; HD-MVAC = high-dose methotrexate, vinblastine, adriamycin plus cisplatin; PCG = paclitaxel, cisplatin, gemcitabine.
- Figure 7.2: Flow chart for the management of metastatic urothelial cancer was adapted.
- Section 7.9 Quality of life - this section was revised to include new data. However, the recommendations did not change.
| Summary of evidence | LE |
| Compared to non-cancer controls, the diagnosis and treatment of bladder cancer has a negative impact on health-related quality of life (HRQoL). | 2a
|