Patients with stage IV disease with involvement of pelvic organs by direct extension or metastases to regional lymph nodes may undergo radical cystectomy with pelvic lymph node dissection.[30,31,32] The extent of lymph node dissection during cystectomy is controversial  because there are no data from prospective trials demonstrating improved outcomes with lymph node dissection. Because T4b tumors cannot generally be completely resected and because lymph node metastases usually signal distant micrometastases, patients with locally advanced bladder cancer are usually given chemotherapy before surgery with the goal of facilitating resection and eliminating micrometastatic disease. While there are data supporting preoperative chemotherapy for clinical stage II and stage III disease, patients with stage IV disease were excluded from most clinical trials investigating the role or preoperative chemotherapy.
External-beam radiation therapy (EBRT) with or without concomitant chemotherapy
Definitive radiation therapy with or without concurrent chemotherapy, evaluated mainly in patients with locally advanced (T2–T4) disease, appears to have minimal curative potential in patients with regional lymph node metastases.[33,34] Patients with evidence of lymph node metastases have therefore generally been excluded from phase III trials of radiation therapy.[35,36]
Urinary diversion or cystectomy for palliation
Urinary diversion may be indicated, not only for palliation of urinary symptoms but also for preservation of renal function in candidates for chemotherapy.
Standard treatment options for patients with any T, any N, M1 disease
Standard treatment options for patients with any T, any N, M1 disease include the following:
- Chemotherapy alone or as an adjunct to local treatment.
- EBRT for palliation.
- Urinary diversion or cystectomy for palliation.
Chemotherapy alone or as an adjunct to local treatment
Cisplatin-based combination chemotherapy regimens are the standard of care for stage IV bladder cancer.[2,3,4,5,6] The only chemotherapy regimens that have been shown to result in longer survival in randomized controlled trials are MVAC, high-dose MVAC, and CMV. GC was compared with MVAC in a randomized controlled trial and no difference in response rate or survival was reported. Of note, patients with good performance status and lymph node-only disease have a low but significant rate of achieving a durable complete remission with MVAC or GC. In the large randomized controlled trial comparing MVAC with GC, for example, 5-year OS in patients with lymph node-only disease was 20.9%.