Summary of Recommendations

Document Overview

Design and created by Guideline Central in participation with the Canadian Urological Association.

Management of Unresectable Locally Advanced and Metastatic Urothelial Carcinoma

Canadian Urological Association

Publication Date: Dec 18, 2024

Page Last Updated: May 6, 2026

STATEMENT 1 The preferred first-line (1L) treatment is the combination of enfortumab vedotin (EV) with pembrolizumab (EV + P).
STATEMENT 2 If progression occurs within one year of PBC and during adjuvant ICI, single-agent EV appears to be a reasonable next option.
STATEMENT 3 For patients who experience progressive disease within six months of completing adjuvant ICI, singleagent EV is a reasonable next option.
STATEMENT 4 In cases where progression occurs more than six months after completing adjuvant ICI therapy, the treatment options may include EV + P, GC + Nivo, or CUAJ • DECEMBER 2024 • VOLUME 18, ISSUE 12 if EV + P not available and patient is cisplatin-ineligible, GCa followed by maintenance avelumab. othEr first-linE options
STATEMENT 5 In platinum-eligible patients, treatment with either GC or GCa followed by maintenance avelumab in those without disease progression remains a reasonable alternative treatment. For platinum-ineligible patients, treatment with pembrolizumab, single-agent chemotherapy, or EV may be discussed.
STATEMENT 6 Although ICIs have been traditionally contraindicated in patients with active autoimmune disorders, chronic immunosuppression, organ dysfunction, and patients who underwent solid organ or hematopoietic stem cell transplant, ICI treatment in these challenging populations may still be possible following a multidisciplinary discussion and careful ongoing assessments for toxicity.
STATEMENT 7 For patients with disease progression after treatment with EV + P in the 1L setting, options for second and later lines of systemic therapy include PBC, erdafitinib, or taxanes.
STATEMENT 8 For patients presenting with disease progression after PBC and immunotherapy — either concurrent cisplatin, gemcitabine and nivolumab or platinum, gemcitabine and maintenance avelumab — treatment options for second and later lines include EV, erdafinitib if FGFR2/3 alteration is found, and taxane singleagent and platinum rechallenge in selected cases.
STATEMENT 9 For patients who did not receive immunotherapy in 1L/maintenance, pembrolizumab is the preferred 2L treatment.
STATEMENT 10 Patients with locally advanced/unresectable disease (cT4b and/or cN1–3) represent a unique subset that can be managed with either purely palliative or potentially curative-intent therapy, depending on the extent of disease, patient fitness, goals of care, and response to 1L chemotherapy. Discussion of such cases in a multidisciplinary tumor board should always be considered to optimize patient outcomes.
STATEMENT 11 For patients who have significant tumor regression and/or low-volume residual metastatic disease after starting systemic palliative 1L treatment, we encourage multidisciplinary discussion to determine whether definitive local management or treatment of oligometastatic disease is warranted.
STATEMENT 12 In patients with OPD on systemic therapy, a multidisciplinary discussion with radiation and surgical oncology may be needed to determine whether local management can be employed so the current line of systemic therapy can be continued.

Document Overview

Document Title: Management of Unresectable Locally Advanced and Metastatic Urothelial Carcinoma

Authoring Society: Canadian Urological Association

Document Publication Date: Dec 18, 2024

Page Last Reviewed/Updated: May 6, 2026

Document Type: Consensus Statement

Country of Publication: Canada

Full Text Freely Available: Yes

Full Text Guideline: www.cua.org/system/files/Guideline-Files/8946v2.pdf

Source Citation: Stecca CE, Chowdhury D, Blais N, Alimohamed N, Wood L, Canil CM, Eigl B, Kulkarni GS, Black PC, Kassouf W, Chung P, North S, Jiang DM, Sridhar SS. 2024 CUA-GUMOC Expert Report: Management of unresectable locally advanced and metastatic urothelial carcinoma. Can Urol Assoc J. 2024 Dec;18(12):379-390. doi: 10.5489/cuaj.8946. PMID: 39641956; PMCID: PMC11623328.

Document Scope, Criteria, and Use Cases

Document Objectives: Since the 2019 publication of the previous consensus statement on the management of metastatic urothelial cancer (mUC), the field has witnessed significant therapeutic advances, marked by the introduction of several new treatment modalities, including immunotherapy (IO), novel antibody drug conjugates (ADC), and targeted therapies. This updated Expert Report aims to incorporate recent data from randomized controlled trials (RCTs) into evidence-based recommendations to guide management of patients with mUC.

Scope: Management, Treatment

Diseases/Conditions (MeSH)

D001749 - Urinary Bladder Neoplasms

D019459 - Urothelium

D001749 - Urinary Bladder Neoplasms

D019459 - Urothelium

Keywords: metastatic, urothelial carcinoma

Target Provider Population: Urologist, medical oncologist, radiation oncologist, pathologist, surgical oncologist, primary care physician, internist

Inclusion Criteria: Male, Female, Adult, Older Adult

Health Care Settings: Ambulatory

Intended Users: Nurse, Nurse Practitioner, Physician, Physician Assistant