Neoadjuvant combination chemotherapy followed by radical cystectomy

A controlled trial of preoperative chemotherapy conducted by the Medical Research Council and the European Organisation for Research and Treatment of Cancer included 976 patients with locally advanced (T3 or T4a) or high-grade muscle-invasive (T2) bladder cancer. Patients were randomly assigned to undergo either definitive treatment immediately or definitive treatment preceded by three cycles of neoadjuvant cisplatin, vinblastine, and methotrexate.[20,21] 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).

A controlled trial of preoperative chemotherapy conducted by the Medical Research Council and the European Organisation for Research and Treatment of Cancer included 976 patients with locally advanced (T3 or T4a) or high-grade muscle-invasive (T2) bladder cancer. Patients were randomly assigned to undergo either definitive treatment immediately or definitive treatment preceded by three cycles of neoadjuvant cisplatin, vinblastine, and methotrexate.[20,21] 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 (HR, 0.84; 95% CI, 0.72–0.99; P = .037). The survival benefit from neoadjuvant chemotherapy compared with definitive treatment alone 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%).[21][Level of evidence A1]

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.[22]

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.[22]

The study showed that the 5-year survival rate was 57% in the group that received neoadjuvant chemotherapy and 43% in the group treated with cystectomy alone. This difference was of borderline statistical significance (two-sided P value = .06 by stratified log-rank test).

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.[22]

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.

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.[22]

Thirty-eight percent of patients who received neoadjuvant chemotherapy had a pathological complete response at the time of surgery, and 85% of those who achieved a pathological complete response were alive at 5 years.

A meta-analysis of ten randomized trials of neoadjuvant chemotherapy included updated data for 2,688 individual patients.[2]

A meta-analysis of ten randomized trials of neoadjuvant chemotherapy included updated data for 2,688 individual patients.[2]

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 rates from 45% to 50% (P = .016).

A meta-analysis of ten randomized trials of neoadjuvant chemotherapy included updated data for 2,688 individual patients.[2]

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 compared with cystectomy alone was associated with a 6.5% absolute benefit in the 5-year OS rate (56.5% vs. 50%; P = .006).[4]