EAU 2025 Guidelines: Upper Urinary Tract Urothelial Carcinoma

What This Guideline Covers

The EAU 2025 Upper Urinary Tract Urothelial Carcinoma guideline provides evidence-based recommendations across 7 topic areas. The key (Strong-rated) recommendations are summarised below; the complete recommendation tables — including Weak recommendations with their strength ratings — plus classification and evidence tables are in the Full Guidelines tab.

Key Recommendations at a Glance

Every Strong-rated EAU recommendation. Where the guideline labels its sections, they are used as sub-headings.

• Evaluate patient and family history to screen patients for Lynch syndrome using modified Amsterdam II criteria.

• Perform germline DNA sequencing in patients with clinical suspicion of hereditary upper urinary tract urothelial carcinomas (UTUC).

• Perform a urethrocystoscopy to rule out bladder tumour.

• Perform computed tomography (CT) or MRI if CT is contraindicated, with urography for diagnosis and staging of all upper tract tumours.

• Perform a chest CT in high-risk tumours (see Figure 1).

• Use diagnostic ureteroscopy if imaging and voided urine cytology are not sufficient for the diagnosis and/or risk-stratification of patients suspected to have upper urinary tract urothelial carcinomas.

• Test for FGFR 2/3 alterations at initial diagnosis in the metastatic setting.

• Use prognostic factors to risk-stratify patients for therapeutic guidance.

• Offer kidney-sparing management as primary treatment option to patients with low-risk tumours.

• Discuss both endoscopic management and distal ureterectomy in low-risk tumours of the distal ureter based on tumour characteristics and shared decision- making with the patients.

• Discuss all patients with suspicion of upper tract urothelial carcinoma (UTUC) on imaging in a multidisciplinary team meeting.

• Perform radical nephroureterectomy (RNU) in patients with high-risk non-metastatic UTUC.

• Offer adjuvant platinum-based chemotherapy after RNU to eligible patients with pT2–T4 and/or pN+ disease.

• Deliver a post-operative bladder instillation of chemotherapy to lower the intravesical recurrence rate in patients without a history of bladder cancer.

• Discuss kidney-sparing management to high-risk patients with imperative indication on a case- by-case basis, in a shared-decision making process with the patient despite the higher risk of disease progression.

• Offer Enfortumab vedotin in combination with pembrolizumab as first-line treatment to patients with advanced/metastatic disease.

• Offer platinum combination chemotherapy to platinum-eligible patients.

• Offer cisplatin-based chemotherapy with gemcitabine/cisplatin or HD-MVAC to cisplatin-eligible patients.

• Offer gemcitabine/carboplatin chemotherapy to cisplatin-ineligible patients.

• Offer maintenance avelumab to patients who did not have disease progression after 4 to 6 cycles of platinum-based combination chemotherapy.

• Offer platinum based combination chemotherapy as second-line treatment of choice if not received in the first-line setting.

• Offer checkpoint inhibitor (pembrolizumab) to patients with disease progression during or after platinum-based combination chemotherapy for metastatic disease who did not receive maintenance avelumab.

• Offer enfortumab vedotin to patients previously treated with platinum- containing chemotherapy and who had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor.

• Offer erdafitinib as an alternative subsequent-line therapy to patients: • previously treated with platinum- containing chemotherapy; • who had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor; • who harbour FGFR DNA genomic alterations (FGFR2/3 mutations or FGFR3 fusions).

• Only offer vinflunine to patients with metastatic disease as second- line treatment if immunotherapy or combination chemotherapy is not feasible. Alternatively, offer vinflunine as third- or subsequent-line treatment.