Lancet. 1999 Aug 14;354(9178):533-40.
Several non-randomised trials have shown that transitional-cell carcinoma of the bladder is a moderately chemosensitive tumour. We investigated whether the addition of neoadjuvant cisplatin-based chemotherapy to radical surgery or radiotherapy would improve survival.
Patients with T2 G3, T3, T4a, N0-NX, or M0 transitional-cell carcinoma of the bladder undergoing curative cystectomy or full-dose external-beam radiotherapy were randomly assigned three cycles of neoadjuvant chemotherapy (cisplatin, methotrexate, and vinblastine, with folinic acid rescue, n=491) or no chemotherapy (n=485). When possible, clinical tumour response was assessed cytoscopically after completion of chemotherapy but before cystectomy or radiotherapy; histopathologically assessed response was on cystectomy samples. We recorded every 6 months locoregional persistence or relapse of tumour, appearance of distant metastases, survival, and cause of death.
Median follow-up of patients still alive was 4.0 years. 485 patients died, and 78.6% of deaths were due to transitional-cell carcinoma. Chemotherapy mortality was 1% and operative (cystectomy) mortality was 3.7%. Kaplan-Meier curves compared by means of the log-rank test gave a calculated absolute difference between groups in 3-year survival of 5.5% (95% CI -0.5 to 11.0, p=0.075; 55.5% for chemotherapy, 50.0% for no chemotherapy). Median survival in the chemotherapy group was 44 months compared with 37.5 months for the no-chemotherapy group. 32.5% of cystectomy samples contained no tumour after neoadjuvant chemotherapy.
Three cycles of neoadjuvant chemotherapy before cystectomy or radiotherapy did not give the 10% improvement in 3-year survival that was judged to be necessary for introduction into routine use. The chemotherapy regimen was associated with a higher pathological complete-response rate in primary tumours, but there was no clear evidence that it would increase survival.
多项非随机试验表明，膀胱移行细胞癌是一种中度化疗敏感肿瘤。我们研究了在根治性手术或放疗基础上加用新辅助顺铂化疗是否能提高生存率。
对接受根治性膀胱切除术或全剂量外照射放疗的T2 G3、T3、T4a、N0 - NX或M0期膀胱移行细胞癌患者，随机分配接受三个周期的新辅助化疗（顺铂、甲氨蝶呤和长春碱，用亚叶酸解救，n = 491）或不接受化疗（n = 485）。可能的话，在化疗完成后但在膀胱切除术或放疗前通过膀胱镜评估临床肿瘤反应；组织病理学评估的反应基于膀胱切除标本。我们每6个月记录一次肿瘤的局部区域持续存在或复发、远处转移的出现、生存情况及死亡原因。
仍存活患者的中位随访时间为4.0年。485例患者死亡，78.6%的死亡归因于膀胱移行细胞癌。化疗死亡率为1%，手术（膀胱切除术）死亡率为3.7%。通过对数秩检验比较的Kaplan - Meier曲线显示，两组3年生存率的计算绝对差异为5.5%（95%可信区间 - 0.5至11.0，p = 0.075；化疗组为55.5%，未化疗组为50.0%）。化疗组的中位生存期为44个月，未化疗组为37.5个月。新辅助化疗后32.5%的膀胱切除标本中无肿瘤。
在膀胱切除术或放疗前进行三个周期的新辅助化疗未能使3年生存率提高10%，而这一提高被认为是引入常规使用所必需的。该化疗方案与原发肿瘤更高的病理完全缓解率相关，但没有明确证据表明它会提高生存率。
