Diagnostic tests and biomarkers for urothelial cancer immunotherapy
- Currently, the evidence does not support routine use of biomarkers to guide BCG therapy in NMIBC. Cystoscopy (with biopsy/transurethral resection (TUR) of bladder tumor as needed), urine cytology, and periodic upper tract imaging should be used to detect recurrence.
- PD-L1 expression by IHC should be used to guide therapy in patients with mUC who are cisplatin-ineligible but eligible for carboplatin. Patients with PD-L1 negative tumors should receive carboplatin-based combination chemotherapy in this setting, while those with PD-L1 positive tumors can receive either immune checkpoint blockade or carboplatin-based chemotherapy.
- MSI-H/dMMR testing should be considered in patients with upper tract and bladder urothelial cancer, especially for patients of younger age and/or with relevant personal or family history to rule out Lynch syndrome, which has implications for genetic counseling.
Non-muscle-invasive bladder cancer
- BCG is recommended for all eligible patients with high-risk NMIBC (including cases with CIS or papillary tumors).
- BCG is also recommended for patients with intermediate-risk NMIBC. However, due to global shortages of BCG, and when BCG is unavailable, the panel recommends intravesical chemotherapy as the first-line therapy for intermediate-risk NMIBC.
- If patients experience recurrence of intermediate-risk NMIBC after a course of intravesical chemotherapy, the panel recommends BCG as second-line intravesical therapy.
- BCG is not recommended for the treatment of patients with low-risk NMIBC.
- BCG should not be administered to patients with active infection or gross hematuria, but BCG may be administered to patients experiencing asymptomatic bacteriuria.
- Best supportive measures should be employed to ensure that patients receive a full, adequate course of BCG.
- Pembrolizumab is approved for the treatment of high-risk BCG-unresponsive CIS with or without papillary tumors.
Muscle-invasive bladder cancer
- The full results of CheckMate 274 are eagerly awaited to guide the potential use of immunotherapy in the adjuvant setting. Active investigation is ongoing into various neoadjuvant and adjuvant strategies, either as single agents or in combination with chemotherapy, radiotherapy, or novel agents.
Advanced/Metastatic Urothelial Carcinoma
- The first-line SOC for mUC is platinum-based chemotherapy. Atezolizumab or pembrolizumab can also be considered as first-line therapy for cisplatin-ineligible patients harboring PD-L1-positive tumors based on a companion assay, or for patients who cannot receive carboplatin (the latter in US only).
- In patients with with locally advanced or mUC that has not progressed with first-line platinum-containing chemotherapy, avelumab maintenance therapy improves OS.
- Pembrolizumab is recommended for the treatment of patients with platinum-refractory mUC based on a significant OS benefit in a randomized phase III trial.
Immunotherapies in development for urothelial cancer
- Participation in clinical trials should be discussed with all patients at any stage of bladder cancer.
Recognition and management of irAEs
- SITC’s guidelines for the management of ICI-related AEs should be consulted for the treatment of irAEs in patients with bladder cancer.
Patient support and QOL
- Patient navigation and PRO tools can help eliminate barriers to oncologic care, enhance patient decision-making, and improve the patient experience during their cancer care. This has been demonstrated in screening outcomes for a variety of malignancies and confirmed in recent studies of NMIBC and MIBC. Combining patient-focused information and educational resources with comprehensive patient-provider conversations can contribute to improved QOL both during treatment and surveillance.
- Comprehensive conversations with patients about all aspects of medical treatment, including financial obligations, could involve multiple clinical and institutional providers. Conversations should continue throughout patient-provider relationships that reflect the evolving nature of treatment timing, options, and patient concerns.
- Urothelial cancer-specific outcome measures for BCG and ICI treatments should be developed, validated, and utilized as tools for patient navigation.
- ICI-specific measures should address a range of treatment protocols and QOL, including ICI alone, combinations with chemotherapy and/or radiation, or any other combination of therapies. Such measures should recognize the often-lengthy nature of bladder cancer treatment and surveillance, along with the potential for adverse effects to occur after the period of initial treatment.
- Practical patient information and education resources are needed for both BCG and ICI treatment. As more patients are treated with ICIs, written and digital educational materials are needed. Patient information resources in written and digital formats are available from bladder cancer and medical education organizations, in addition to materials provided by the providing clinic.
- There is now an opportunity to develop, study, and deploy digital/mobile technologies to increase patient awareness and reporting of BCG- and ICI-related AEs. Innovation in patient-provider communication and application of technology to PRO/QOL communication could affect patient care for initial and follow-up of patients with urothelial cancer.
May 24, 2021
Last Updated Month/Year
August 15, 2023
Supplemental Implementation Tools
External Publication Status
Country of Publication
Female, Male, Adult, Older adult
Health Care Settings
Ambulatory, Home health, Hospital
Physician, nurse practitioner, nurse, physician assistant
D019459 - Urothelium
immunotherapy, chemotherapy, radiotherapy, Clinical Practice Guideline, Urothelial Cancer, intravesical Bacillus Calmette Guerin