Updated: April 2008

1. Radical Cystectomy

Radical cystectomy is the most frequent curative treatment option in North America with a five year survival range from 35% for patients with node-positive disease to up to 89% for T2 muscle-invasive disease. ⁽¹⁵⁾If a radical cystectomy is to be performed, ideally it should be initiated within 4-6 weeks, but no later than 3 months and should include an extended pelvic lymph node dissection.

2. External Beam Radiation Therapy

An alternative to cystectomy, external beam radiation therapy offers a potentially curative treatment approach with the possibility of bladder preservation. However, careful follow-up with cystectomy reserved for salvage is essential. It has been reported that between 15 and 25% of patients require salvage cystectomy for either recurrence or bladder contracture. ⁽¹⁶⁾ Single modality external beam radiation therapy is an option for patients whoa re interested in bladder preservation or who are unsuitable for surgery because of advanced age or concurrent medical problems. Five-year survival range for single modality external beam radiation therapy is 20-40% in large series.⁽¹⁷⁾ Some patients may be eligible for a combined modality approach (see below).

3. Combined Modality Therapy Including Chemotherapy

a) Neoadjuvant Chemotherapy

The rationale for giving chemotherapy before definitive treatment is to treat micrometastatic disease that may be present at diagnosis. In addition, chemotherapy is often better tolerated given before surgery or radical radiotherapy. A recent meta-analysis using updated data from 11 randomized controlled trials showed a 5% improvement in survival at five years (from 45% to 50%) with neoadjuvant platinum-based combination chemotherapy followed by surgery. ⁽¹⁸⁾ Appropriate patients have invasive urothelial carcinoma with no clinical evidence of nodal or metastatic disease who are to undergo a curative cystectomy, an ECOG performance status of 0 -1 and adequate renal function [stenting for hydronephrosis should be considered early] (see UGUNAJPG protocol).

b) Concurrent Chemotherapy and Radiotherapy

The role of concurrent chemo-radiotherapy is uncertain. The only randomized study of cisplatin concurrent chemotherapy was negative for survival, but did demonstrate improved local control. ⁽¹⁹⁾Multiple non-randomized studies demonstrate similar survival rates with tri-modality therapy to those found with radical cystectomy. This approach may be appropriate for selected patients who are interested in bladder preservation or who decline or are not suitable candidates for surgery. (see GUBPRT and GUBPWRT protocols)

c) Adjuvant Chemotherapy

A number of trials have been conducted comparing cystectomy alone to cystectomy with adjuvant chemotherapy. Many of these trials were underpowered, closed prematurely or used sub-optimal chemotherapy. An individual patient data meta-analysis has been done looking at the results of 491 patients from six trials.⁽²⁰⁾ The analysis showed a 25% relative risk reduction in death, however, the authors felt that the available data is too limited for a treatment decision to be based upon. Therefore, adjuvant chemotherapy is not routinely recommended. Patients should be enrolled in clinical trials whenever possible. Selected high risk patients (e.g. extravesical extension, node-positive) who are likely to tolerate platinum-based chemotherapy and who understand the limitations of the available data can be considered for treatment. (see UGUAJPG)

d) Tri-Modality Therapy

Bladder-sparing by means of 'tri-modality' therapy comprises aggressive TURBT followed by induction chemo-radiotherapy, cystoscopic reassessment with immediate cystectomy for those not in complete remission, and further chemoradiotherapy for those in remission.^{(21, 22)} Multiple non-randomized studies demonstrate similar survival rates with tri-modality therapy to those found with radical cystectomy. Patients considered for this approach must be compliant with frequent follow up visits. Individual cases should be presented at GU Conference for multi-modality consideration.

All superscript references in this chapter, refer to the list of References for Bladder.