Upper urinary tract urothelial carcinoma 2020
Summary of changes
The literature for the complete document has been assessed and updated, whenever relevant. Conclusions and recommendations have been rephrased and added to throughout the current document.
Key changes for the 2020 print:
- Section 3.1 – Epidemiology – has been expanded, resulting changes in Figure 3.1 and the addition of two new recommendations
3.4 Summary of evidence and recommendations for epidemiology, aetiology and pathology
| Summary of evidence | LE |
| Aristolochic acid and smoking exposure increases the risk for UTUC. | 2 |
| Patients with Lynch syndrome are at risk for UTUC. | 3 |
| Recommendations | Strength rating |
| Evaluate patient and family history based on the Amsterdam criteria to identify patients with upper tract urothelial carcinoma. | Weak |
| Evaluate patient exposure to smoking and aristolochic acid. | Weak |
- Chapter 6 – Prognosis – additional information has been added, resulting in changes to Figure 6.1 and an additional recommendation.
6.7 Summary of evidence and guidelines for prognosis
| Summary of evidence | LE |
| Chronological age should not preclude radical nephroureterectomy with curative intent, where indicated. | 3 |
| Important prognostic factors include hydronephrosis, tumour multifocality, size, stage, grade, lymph node metastasis, lymphovascular invasion and variant histology. | 3 |
| Recommendations | Strength rating |
| Use pre-operative factors to risk-stratify patients for therapeutic guidance. | Weak |
- Chapter 7 – Disease management, has been restructured, including new information on adjuvant and neoadjuvant therapies. Both Figures 7.1 and 7.2 have been adapted and a number of new recommendations have been added.
7.1.6 Summary of evidence and guidelines for management of high-risk non-metastatic UTUC
| Summary of evidence | LE |
| Failure to completely remove the bladder cuff increases the risk of bladder cancer recurrence. | 3 |
| Lymphadenectomy improves survival in muscle-invasive UTUC. | 3 |
| Peri-operative chemotherapy may improve survival. | 3 |
| Single post-operative intravesical instillation of chemotherapy lowers the bladder cancer recurrence rate. | 1 |
| Recommendations | Strength rating |
| Perform radical nephroureterectomy (RNU) in patients with high-risk non-metastatic upper tract urothelial carcinoma (UTUC). | Strong |
| Perform open RNU in non-organ-confined UTUC. | Weak |
| Remove the bladder cuff in its entirety. | Strong |
| Perform a template-based lymphadenectomy in patients with muscle-invasive UTUC. | Strong |
| Offer peri-operative chemotherapy to patients with muscle-invasive UTUC. | Weak |
| Deliver a post-operative bladder instillation of chemotherapy to lower the intravesical recurrence rate. | Strong |
- Section 7.2 – Metastatic disease has been expanded to include the latest information on immunotherapy, both in a first- and second-line setting, resulting in a new summary table.
7.2.4 Summary of evidence and guidelines for the treatment of metastatic UTUC
| Summary of evidence | LE |
| Radical nephroureterectomy may improve quality of life and oncologic outcomes in select metastatic patients. | 3 |
| Cisplatin-based combination chemotherapy can improve median survival. | 2 |
| Single-agent and carboplatin-based combination chemotherapy are less effective than cisplatin-based combination chemotherapy in terms of complete response and survival. | 3 |
| Non-platinum combination chemotherapy has not been tested against standard chemotherapy in patients who are fit or unfit for cisplatin combination chemotherapy. | 4 |
| 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. | 1b |
| PD-L1 inhibitor atezolizumab has been FDA approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase II trial. | 2a |
| PD-1 inhibitor nivolumab has been approved for patients that have progressed during or after previous platinum-based chemotherapy based on the results of a phase II trial. | 2a |
| PD-1 inhibitor pembrolizumab has been approved for patients with advanced or metastatic UC 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 UC 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 |
| Offer radical nephroureterectomy as a palliative treatment to symptomatic patients with resectable locally advanced tumours. | Weak |
| 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 unfit for cisplatin | |
| Offer checkpoint inhibitors pembrolizumab or atezolizumab depending on PDL-1 status. | Weak |
| Offer carboplatin combination chemotherapy if PD-L1 is negative. | Strong |
| Second-line treatment | |
| Offer checkpoint inhibitor (pembrolizumab) to patients with disease progression during or after platinum-based combination chemotherapy for metastatic disease. | Strong |
| Offer checkpoint inhibitor (atezolizumab) to patients with disease progression during or after platinum-based combination chemotherapy for metastatic disease. | 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; PD-L1 = programmed death ligand 1; PCG = paclitaxel, cisplatin, gemcitabine.