From the Guidelines
The prognosis of invasive high-grade urothelial carcinoma is generally poor, with five-year survival rates varying significantly based on stage at diagnosis, and treatment typically involves radical cystectomy with pelvic lymph node dissection for localized disease, often combined with neoadjuvant cisplatin-based chemotherapy regimens. For muscle-invasive disease (stages T2-T4), five-year survival ranges from 30-50%, while metastatic disease has a much lower survival rate of approximately 5-15% 1. The most recent guidelines from the European Association of Urology recommend first-line treatment for platinum-fit patients with cisplatin-containing combination chemotherapy with GC or HD-MVAC, and maintenance treatment with the PD-L1 inhibitor avelumab for patients achieving stable disease or better after first-line platinum-based chemotherapy 1.
Factors Influencing Prognosis
The prognosis is influenced by several factors including:
- Tumor stage
- Lymph node involvement
- Presence of distant metastases
- Patient age
- Performance status
- Response to treatment
Treatment Approaches
Treatment approaches for invasive high-grade urothelial carcinoma include:
- Radical cystectomy with pelvic lymph node dissection for localized disease
- Neoadjuvant cisplatin-based chemotherapy regimens such as dose-dense MVAC or gemcitabine plus cisplatin
- Platinum-based combination chemotherapy with methotrexate–vinblastine–doxorubicin–cisplatinum or gemcitabine–cisplatinum for metastatic disease
- Immunotherapy with PD-1/PD-L1 inhibitors like pembrolizumab or atezolizumab for those who are cisplatin-ineligible or as second-line therapy
Surveillance and Follow-Up
The current guideline recommends a CT scan every 6 mo until the third year, with annual imaging thereafter, including the upper urinary tract (UUT) 1. The time schedule for surveillance is based on low-level evidence, although most recurrences tend to occur in the first years after definitive treatment.
Quality of Life
Treatment of muscle-invasive and metastatic bladder cancer has an impact on health-related quality of life (HRQoL), which should be assessed at baseline and after treatment using a validated questionnaire for bladder cancer 1.
From the FDA Drug Label
The major efficacy outcome measures were OS and PFS as assessed by BICR according to RECIST v1. 1. The trial demonstrated statistically significant improvements in OS, PFS, and ORR for patients randomized to KEYTRUDA in combination with enfortumab vedotin as compared to platinum-based chemotherapy. Efficacy results were consistent across all stratified patient subgroups Table 75 and Figures 16 and 17 summarize the efficacy results for KEYNOTE-A39 OS Number (%) of patients with event133 (30%)226 (51%) Median in months (95% CI)31.5 (25.4, NR)16.1 (13.9,18. 3) Hazard ratio* (95% CI)0.47 (0.38,0.58) p-Value†<0.0001 PFS Number (%) of patients with event223 (50%)307 (69%) Median in months (95% CI)12.5 (10.4,16.6)6.3 (6.2,6.5) Hazard ratio* (95% CI)0.45 (0.38,0.54) p-Value†<0.0001 Confirmed Objective Response Rate‡ ORR§ % (95% CI)68% (63,72)44% (40,49) p-Value¶<0. 0001 Complete response29%12% Partial response39%32%
The prognosis of invasive high-grade urothelial carcinoma is poor without treatment.
- Overall Survival (OS): The median OS was 16.1 months for patients treated with platinum-based chemotherapy and 31.5 months for patients treated with KEYTRUDA in combination with enfortumab vedotin.
- Progression-Free Survival (PFS): The median PFS was 6.3 months for patients treated with platinum-based chemotherapy and 12.5 months for patients treated with KEYTRUDA in combination with enfortumab vedotin.
- Objective Response Rate (ORR): The ORR was 44% for patients treated with platinum-based chemotherapy and 68% for patients treated with KEYTRUDA in combination with enfortumab vedotin. 2
From the Research
Prognosis of Invasive High-Grade Urothelial Carcinoma
The prognosis of invasive high-grade urothelial carcinoma varies depending on several factors, including the site of metastatic recurrence, lymphovascular invasion, tumor grade, and nodal stage.
- The 5-year overall survival (OS) rate for patients with muscle-invasive urothelial bladder cancer was 61.8% 3.
- Lymphovascular invasion, high tumor grade, and high nodal stage are independent predictors of recurrence in patients with muscle-invasive urothelial carcinoma 4.
- The site of metastatic recurrence also impacts prognosis, with recurrences in the liver, bone, and multiple sites having a worse prognosis than those in lymph nodes 5.
- Upper tract urothelial carcinoma (UTUC) has a better prognosis than bladder cancer (BC) when stage and grade are considered simultaneously, with a 5-year cancer-specific survival (CSS) rate of 61.0% for UTUC and 49.8% for BC 6.
- The management of high-grade T1 urothelial carcinoma is complex, with a high rate of recurrence, progression, and cancer-specific mortality, and recent data have described expanding options for salvage intravesical therapy and bladder preservation 7.
Factors Affecting Prognosis
Several factors affect the prognosis of invasive high-grade urothelial carcinoma, including:
- Lymphovascular invasion: presence of lymphovascular invasion is a predictor of metastatic recurrence and poor prognosis 5, 4.
- Tumor grade: high tumor grade is an independent predictor of recurrence and poor prognosis 4.
- Nodal stage: high nodal stage is an independent predictor of recurrence and poor prognosis 4.
- Site of metastatic recurrence: recurrences in the liver, bone, and multiple sites have a worse prognosis than those in lymph nodes 5.