Guidelines

Upper Urinary Tract Urothelial Cell Carcinoma

1. INTRODUCTION

1.1. Aim and scope

The European Association of Urology (EAU) Non-muscle-invasive Bladder Cancer (NMIBC) Guidelines Panel has compiled these clinical guidelines to provide urologists with evidence-based information and recommendations for the management of upper urinary tract urothelial carcinoma (UTUC). Separate EAU guidelines documents are available addressing non-muscle-invasive bladder cancer [1], muscle-invasive and metastatic bladder cancer (MIBC) [2], and primary urethral carcinoma [3].

It must be emphasised that clinical guidelines present the best evidence available to the experts but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account. Guidelines are not mandates and do not purport to be a legal standard of care.

1.2. Panel composition

The European Association of Urology (EAU) Guidelines Panel on NMIBC consists of an international multidisciplinary group of clinicians, including urologists, uro-oncologists, a radiologist, a pathologist, and a statistician. Members of this panel have been selected based on their expertise and to represent the professionals treating patients suspected of harbouring urothelial carcinoma (UC). In the course of 2021 two patient representatives have formally joined the NMIBC Panel. All involved in the production of this document have submitted potential conflict of interest statements, which can be viewed on the EAU website Uroweb: https://uroweb.org/guideline/upper-urinary-tract-urothelial-cell-carcinoma/.

1.3. Available publications

A quick reference document (Pocket guidelines) is available in print and as an app for iOS and Android devices, presenting the main findings of the UTUC Guidelines. These are abridged versions which may require consultation together with the full text version. Several scientific publications are available as are a number of translations of all versions of the EAU UTUC Guidelines, the most recent scientific summary was published in 2020 [4]. All documents are accessible through the EAU website Uroweb: https://uroweb.org/guideline/
upper-urinary-tract-urothelial-cell-carcinoma/
.

1.4. Publication history & summary of changes

The first EAU Guidelines on UTUC were published in 2011. This 2022 publication presents a limited update of the 2021 version.

1.4.1. 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 2022 print can be found in:

  • Section 3.1 – Epidemiology, due to the inclusion of additional data on mismatch repair testing, Figure 3.1: Selection of patients with UTUC for Lynch syndrome screening during the first medical Interview, was revised.
  • Chapter 6 – Prognosis, considerable data has been added;
  • 7.1.2 Management of high-risk non-metastatic UTUC – New Section 7.1.3.2.2 Immunotherapy, was added.
  • 7.2.3 Systemic treatments. This section has been completely restructured and updated, resulting in a number of changes to the Summary of changes and guidelines for the treatment of metastatic UTUC.
7.2.4 Summary of evidence and guidelines for the treatment of metastatic UTUC

Summary of evidence

LE

Cisplatin-containing combination chemotherapy is standard in advanced or metastatic patients fit enough to tolerate cisplatin.

1b

Maintenance avelumab is associated with an OS advantage compared with best supportive care in patients who did not have disease progression after 4 to 6 cycles of gemcitabine plus cisplatin or carboplatin.

1b

PD-1 inhibitor pembrolizumab has been approved for patients who have progressed during or after previous platinum-based chemotherapy and did not receive previous immune therapy based on the results of a phase III trial.

1b

PD-L1 inhibitor atezolizumab has been approved for patients that have progressed during or after previous platinum-based chemotherapy and did not receive previous immune therapy 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 and did not receive previous immune therapy based on the results of a phase II trial.

2a

Erdafitinib improves OS in in platinum-refractory patients with locally advanced or metastatic UC and FGFR DNA genomic alterations (FGFR2 or 3 mutations, or FGFR3 fusions).

2a

Recommendation

Strength rating

First-line treatment for cisplatin-eligible patients

Use maintenance avelumab in patients who did not have disease progression after 
4 to 6 cycles of gemcitabine plus cisplatin.

Strong

First-line treatment in patients unfit for cisplatin

Use maintenance avelumab in patients who did not have disease progression after
4 to 6 cycles of gemcitabine plus carboplatin.

Strong

Second-line treatment

Offer erdafitinib in platinum-refractory tumours with FGFR alterations.

Strong

FGFR = fibroblast growth factor receptors.