Bladder Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stages II and III Bladder Cancer Treatment
In a retrospective analysis from a single institution, elderly patients (≥70 years) in good general health were found to have clinical and functional results after radical cystectomy similar to younger patients.
After radical cystectomy, however, an approximate 30% to 40% risk of recurrence still exists for patients with muscle-invasive disease, even at centers of excellence.[6,7,8] Five-year overall survival (OS) has generally been reported to be in the range of 50% to 60% but varies by stage. The addition of preoperative radiation therapy to radical cystectomy did not result in any survival advantage when compared with radical cystectomy alone in a prospective randomized trial.
Neoadjuvant combination chemotherapy followed by radical cystectomy
Because bladder cancer commonly recurs with distant metastases, systemic chemotherapy administered before or after cystectomy has been evaluated as a means of improving outcome. Administration of chemotherapy before cystectomy (i.e., neoadjuvant chemotherapy) may be preferable to postoperative treatment because tumor downstaging from chemotherapy may enhance resectability; occult metastatic disease may be treated as early as possible; and chemotherapy may be better tolerated. Currently, the body of evidence supporting preoperative chemotherapy is much stronger than the evidence supporting postoperative chemotherapy.
Evidence (neoadjuvant combination chemotherapy followed by radical cystectomy):
- A controlled trial of preoperative chemotherapy conducted by the Medical Research Council and the European Organization for Research and Treatment of Cancer randomly assigned 976 patients with locally advanced (T3 or T4a) or high-grade muscle-invasive (T2) bladder cancer to undergo either definitive treatment immediately or definitive treatment preceded by three cycles of neoadjuvant cisplatin, vinblastine, and methotrexate.[19,20] In this study, definitive treatment consisted of radical cystectomy (n = 428), radiation therapy (n = 403), or preoperative radiation therapy followed by radical cystectomy (n = 66).
- At a median follow-up of 8.0 years for patients still alive, OS was significantly greater in the arm randomly assigned to receive neoadjuvant chemotherapy (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.72–0.99; P = .037). The survival benefit from neoadjuvant chemotherapy conferred a 6% absolute increase in the likelihood of being alive at 3 years (56% vs. 50%), 5 years (49% vs. 43%), and 10 years (36% vs. 30%).[Level of evidence: 1iiA]
- A randomized study conducted by the Southwest Oncology Group compared three cycles of neoadjuvant cisplatin, methotrexate, vinblastine, and doxorubicin administered before cystectomy with cystectomy alone in 317 patients with stage T2 to stage T4a bladder cancer.
- The study showed that 5-year survival was 57% in the group that received neoadjuvant chemotherapy and 43% in the group treated with cystectomy alone, which is a difference of borderline statistical significance (two-sided P value = .06 by stratified log-rank test).
- No deaths were associated with neoadjuvant chemotherapy, and there was no difference in the rate or severity of postoperative complications in patients who received immediate surgery and in those who received preoperative chemotherapy. Cystectomy was performed as planned for 82% of patients assigned to preoperative chemotherapy and 81% of those assigned to cystectomy alone. This study provided evidence that preoperative chemotherapy does not prevent patients from undergoing cystectomy and does not increase the risk of perioperative complications.
- Thirty-eight percent of patients who received neoadjuvant chemotherapy had a pathologic complete response at the time of surgery, and 85% of those achieving a pathologic complete response were alive at 5 years.
- A meta-analysis of ten randomized trials of neoadjuvant chemotherapy, including updated data for 2,688 individual patients, showed that cisplatin-based combination chemotherapy was associated with a significant 13% relative reduction in the risk of death and resulted in an improvement in 5-year survival from 45% to 50% (P = .016). Neoadjuvant single-agent cisplatin was not associated with any survival benefit in the meta-analysis.
- A subsequent meta-analysis evaluated a nearly identical body of data (11 randomized controlled trials enrolling a total of 2,605 patients) and reached similar conclusions. When the analysis was limited to the eight trials that used multiagent, cisplatin-based chemotherapy, neoadjuvant chemotherapy was associated with a 6.5% absolute benefit in 5-year OS (50% vs. 56.5%; P = .006).