What is the adjuvant therapy for muscle-invasive bladder cancer (MIBC)?

From the Guidelines

Adjuvant chemotherapy is recommended for patients with muscle-invasive bladder cancer (MIBC) following radical cystectomy, particularly for those with pathologic T3/T4 disease or node-positive disease, with the preferred regimen being cisplatin-based combination chemotherapy, specifically gemcitabine plus cisplatin (GC) or dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) 1.

Key Considerations

• The choice of adjuvant chemotherapy regimen should be based on the patient's overall health, renal function, and ability to tolerate cisplatin-based therapy.
• Neoadjuvant chemotherapy is preferred over adjuvant-based chemotherapy due to higher level of evidence data, with dose-dense MVAC being preferred over standard MVAC based on category 1 evidence showing improved tolerance and efficacy 1.
• For patients who are cisplatin-ineligible, carboplatin-based regimens may be considered, although they are less effective, and adjuvant immunotherapy with nivolumab may be an option for high-risk patients who received neoadjuvant cisplatin chemotherapy 1.

Treatment Regimens

• Gemcitabine plus cisplatin (GC): cisplatin 70 mg/m² on day 1 and gemcitabine 1000 mg/m² on days 1,8, and 15, repeated every 28 days for 4 cycles.
• Dose-dense MVAC: methotrexate 30 mg/m², vinblastine 3 mg/m², doxorubicin 30 mg/m², and cisplatin 70 mg/m² with G-CSF support, given every 14 days for 4 cycles.

Rationale for Adjuvant Therapy

• To eliminate micrometastatic disease that may be present after surgery, as approximately 50% of MIBC patients develop metastases despite radical surgery, with adjuvant chemotherapy showing a 30% reduction in the risk of death in appropriate candidates 1.
• To improve overall survival and disease-free survival in patients with high-risk disease, such as those with pathologic T3/T4 disease or node-positive disease 1.

From the Research

Adjuvant Therapy for Muscle Invasive Bladder Cancer

• Adjuvant chemotherapy may be considered in selected patients with muscle-invasive bladder cancer (MIBC) who have undergone radical cystectomy, particularly those with high-risk features such as pT3-T4 or N+ disease 2, 3, 4.
• The use of adjuvant chemotherapy has been shown to improve progression-free survival (PFS) and overall survival (OS) in patients with MIBC, with a significant reduction in the risk of recurrence and death 4.
• Various adjuvant chemotherapy regimens have been studied, including gemcitabine and cisplatin, and gemcitabine/cisplatin/paclitaxel (GCP) combination, with the GCP combination showing significant improvement in both PFS and OS 4.
• However, the optimal adjuvant chemotherapy regimen for MIBC remains unclear, and further studies are needed to establish the most effective approach 2, 4.
• Recent studies have also explored the use of immune checkpoint inhibitors in the adjuvant setting, with promising results, and their addition to neo-adjuvant chemotherapy and post-cystectomy adjuvant therapy may be beneficial 5.
• The choice of adjuvant therapy should be individualized based on patient factors, such as performance status, comorbidities, and tumor characteristics, as well as the presence of high-risk features such as lymph node invasion or hydronephrosis 2, 6, 3.

Neoadjuvant Chemotherapy

• Neoadjuvant chemotherapy with cisplatin-based regimens, such as dose-dense MVAC or gemcitabine and cisplatin, has been shown to improve overall survival in patients with MIBC, particularly those with cT2-T4N0 disease 2, 6.
• The use of neoadjuvant chemotherapy can also downstage the tumor, with a significant proportion of patients achieving a complete pathological response (pCR) 2, 6.
• However, the value of neoadjuvant treatment in node-positive MIBC is not clearly demonstrated, and further studies are needed to establish its benefit in this setting 2.

Future Directions

• Further research is needed to establish the optimal adjuvant chemotherapy regimen for MIBC, as well as the role of immune checkpoint inhibitors in the adjuvant setting 2, 4, 5.
• The development of molecular tumor subtyping may support the selection of novel agents for neoadjuvant or adjuvant strategies, and personalized medicine approaches may improve outcomes for patients with MIBC 2, 5.