From the Guidelines
Stage four urothelial carcinoma is generally not considered curable, but it is treatable with therapies that can extend life and improve quality of life. Treatment typically involves systemic therapies such as platinum-based chemotherapy regimens (like gemcitabine with cisplatin or carboplatin), immunotherapy agents (such as pembrolizumab, atezolizumab, or nivolumab), and targeted therapies (like erdafitinib for FGFR mutations or enfortumab vedotin) 1. These treatments aim to control the cancer's spread and manage symptoms. The five-year survival rate for stage four urothelial carcinoma is approximately 5-15%, though individual outcomes vary based on factors like overall health, specific cancer characteristics, and response to treatment 1. Some patients may achieve long-term disease control or remission, even if complete cure is rare.
Key Considerations
- The advanced stage indicates that cancer has spread beyond the bladder to distant organs or lymph nodes, making complete surgical removal impossible.
- Patients should work closely with oncologists to develop personalized treatment plans that balance extending life with maintaining quality of life, potentially including clinical trials of newer therapies.
- According to the latest guidelines, cisplatin-based chemotherapy is recommended as first-line treatment for eligible patients, while carboplatin-based regimens are recommended for those unfit to receive cisplatin 1.
- Immunotherapy agents, such as atezolizumab or pembrolizumab, may be considered as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1 1.
- Treatment should continue for 2 years for pembrolizumab and until progression for atezolizumab, with maintenance avelumab being a preferential option compared to upfront ICIs in PD-L1 positive patients 1.
Treatment Options
- Platinum-based chemotherapy regimens
- Immunotherapy agents (e.g. pembrolizumab, atezolizumab, or nivolumab)
- Targeted therapies (e.g. erdafitinib for FGFR mutations or enfortumab vedotin)
- Maintenance avelumab for patients with PD-L1 positive tumors 1
From the FDA Drug Label
The efficacy of KEYTRUDA in combination with enfortumab vedotin was evaluated in KEYNOTE-869 (NCT03288545), an open-label, multi-cohort (dose escalation cohort, Cohort A, Cohort K) study in patients with locally advanced or metastatic urothelial cancer who were ineligible for cisplatin-containing chemotherapy and received no prior systemic therapy for locally advanced or metastatic disease
The major efficacy outcome measures were ORR and DoR as assessed by BICR according to RECIST v1. 1.
Efficacy results are presented in Table 76 below.
Table 76: Efficacy Results in KEYNOTE-869, Combined Dose Escalation Cohort, Cohort A, and Cohort K
EndpointKEYTRUDA in combinationwith Enfortumab Vedotinn=121
Confirmed ORR (95% CI)68% (58. 7,76.0)
Complete response rate12%
Partial response rate55%
The FDA drug label does not provide information on whether stage four urothelial carcinoma is curable. While the label reports response rates and durations of response for patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin, cure is not mentioned as an outcome. Therefore, no conclusion can be drawn about the curability of stage four urothelial carcinoma based on this information 2.
From the Research
Treatment Options for Stage Four Urothelial Carcinoma
- The treatment for stage four urothelial carcinoma (UC) depends on various factors, including the patient's overall health, kidney function, and the presence of specific biomarkers such as PD-L1 3.
- Platinum-based chemotherapy, including gemcitabine and cisplatin, is a standard treatment option for cisplatin-fit patients 3.
- For cisplatin-unfit patients, the combination of gemcitabine and carboplatin has shown clinical activity, although it is associated with considerable toxicity 4, 5.
- Immune checkpoint inhibitors, such as atezolizumab and pembrolizumab, have been approved for use in patients with advanced UC, including those who are cisplatin-ineligible or have high PD-L1 expression 6, 3.
Curability of Stage Four Urothelial Carcinoma
- Unfortunately, stage four UC is generally considered incurable, with current treatments focusing on improving symptoms, slowing disease progression, and extending overall survival 7.
- While some patients may experience durable responses to treatment, the disease often develops resistance to therapy, making it challenging to achieve long-term remission 7.
- Ongoing research is exploring new treatment strategies, including combination therapies and targeted agents, to improve outcomes for patients with advanced UC 6, 3, 7.
Prognosis and Survival
- The prognosis for stage four UC is generally poor, with a median overall survival of around 8-16 months, depending on the treatment and patient characteristics 4, 5.
- However, some patients may experience longer survival times, and individual outcomes can vary significantly depending on various factors, including the effectiveness of treatment and the patient's overall health 4, 5.