v2.1 Update

Full approval of nivolumab in this setting was granted in August, 2021 [Ref 6].

v2.2 Update

In August 2021, the indication for pembrolizumab for the treatment of patients with metastatic or locally advanced mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was converted to full approval and revised to no longer specify PD-L1 expression status for eligibility [Ref 3].

v2.1 Update

Recommendation modified to include information on the approval of nivolumab as adjuvant treatment for patients with surgically resected, high-risk MIBC, as noted below:

• For patients with MIBC at high risk for recurrence after radical resection (ypT2-ypT4a or ypN+ for patients who received neoadjuvant cisplatin-based chemotherapy or pT3-pT4a or pN+ for patients who did not receive neoadjuvant cisplatin-based chemotherapy and who also either were ineligible for or refused adjuvant cisplatin-based chemotherapy) adjuvant nivolumab extends DFS as demonstrated in CheckMate 274 (LE: 2). Neoadjuvant therapy with cisplatin-based combination chemotherapy remains the treatment paradigm for curative intent therapy when surgery is considered; the data of CheckMate 274 are insufficient to conclude that adjuvant immunotherapy alone can replace the current practice which is known to maximize survival. Active investigation is ongoing into various additional neoadjuvant and/or adjuvant strategies (and bladder preservation), either as single agents, or in combination with chemotherapy, radiotherapy, or novel agents.

v2.1 Update

Since guideline publication, the FDA approved nivolumab for the adjuvant treatment of patients with urothelial cancer (UC) who are at high risk of recurrence after undergoing radical resection in August 2021 [Ref 6].

Last Reviewed 10/19/2024 (v2.4 Update)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Urothelial Cancer Immunotherapy Guideline Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines.

v2.4 Update Summary

• The FDA granted accelerated approval of enfortumab vedotin in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer in December 2023 [Ref 3, 158].

• The FDA granted approval of nivolumab in combination with cisplatin and gemcitabine as first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma in March 2024 [Ref 6].

• Data have been reported indicating similar responses to ICI therapy regardless of FGFR3 mutation status for patients with metastatic urothelial cancer [Ref 159].

• The FDA granted approval of nogapendekin alfa inbakicept with BCG for adult patients with BCG-unreseponsive NMIBC with carcinoma in situ with or without papillary tumors in April 2024 [Ref 160].

v2.3 Update Summary

• Atezoluzimab for the treatment of cisplatin- and platinum-ineligible patients with mUC was voluntary withdrawn by the manufacturer in November, 2022 [Ref 161].

• The FDA granted approval of nadofaragene firadenovec for the treatment of BCG-unresponsive NMIBC with CIS with or without papillary tumors in December 2022 [Ref 162].

• The FDA granted accelerated approval of enfortumab vedotin with pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy in April 2023 [Ref 3, 158].

v2.2 Update Summary * The indication of pembrolizumab for the treatment of patients with mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was revised in August 2021 to no longer specify PD-L1 status for eligibility [Ref 3].

v2.1 Update Summary * The FDA granted approval of nivolumab for the treatment of patients with urothelial cancer who are at high risk of recurrence after undergoing radical resection in August 2021 [Ref 6].

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Update 8-1-2023

The mUC treatment algorithm has been updated based on the label change for pembrolizumab, the voluntary withdrawal of the atezolizumab indication, and the approval of pembrolizumab plus enfortumab vedotin for the treatment of patients with advanced mUC.

Updated mUC treatment algorithm