Cochrane Database Syst Rev. 2006 Apr 19;2006(2):CD006018. doi: 10.1002/14651858.CD006018.
Controversy exists as to whether adjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite a number of randomised controlled trials.
To evaluate the effect of adjuvant chemotherapy in invasive bladder cancer. We conducted a systematic review and meta-analysis of updated individual patient data from all available randomised controlled trials comparing local treatment plus adjuvant chemotherapy versus the same local treatment alone.
MEDLINE and Cancerlit searches were supplemented with information from registers and hand searching meeting proceedings and also by discussion with relevant trialists and organisations. They have been regularly updated until September 2004.
Trials that aimed to randomise patients with biopsy proven invasive (i.e. clinical stage T2-T4a) transitional cell carcinoma of the bladder to receive local definitive treatment with or without adjuvant chemotherapy were eligible for inclusion.
We collected, validated and re-analysed updated data on all randomised patients from all available randomised trials, including 491 patients from 6 RCTs. For all outcomes, we obtained overall pooled hazard ratios using the fixed effects model. To explore the potential impact of trial design, we pre-planned analyses that grouped trials by important aspects of their design that might influence the treatment effect. To investigate any differences in effect by pre-defined patient sub-groups, we used a stratified logrank analysis on the primary endpoint of survival.
Analyses were based on 491 patients from six trials, representing 90% of all patients randomised in cisplatin-based combination chemotherapy trials and 66% of patients from all eligible trials. The power of this meta-analysis is clearly limited. The overall hazard ratio for survival of 0.75 (95%CI 0.60-0.96, p=0.019) suggests a 25% relative reduction in the risk of death for chemotherapy compared to that on control. Cox regression suggests that small imbalances in patient characteristics do not bias the results in favour of chemotherapy. However, the impact of trials that stopped early, of patients not receiving allocated treatments or not receiving salvage chemotherapy is less clear.
AUTHORS' CONCLUSIONS: This IPD meta-analysis provides the best evidence currently available on the role of adjuvant chemotherapy for invasive bladder cancer. However, at present there is insufficient evidence on which to reliably base treatment decisions. These results highlight the urgent need for further research into the use of adjuvant chemotherapy. The results of appropriately sized randomised trials, such as the ongoing EORTC-30994 trial are needed before any definitive conclusions can be drawn.
尽管有多项随机对照试验，但对于辅助化疗是否能提高浸润性膀胱癌患者的生存率仍存在争议。
评估辅助化疗对浸润性膀胱癌的疗效。我们对所有可用随机对照试验中更新的个体患者数据进行了系统评价和荟萃分析，比较局部治疗加辅助化疗与单纯相同局部治疗的效果。
通过检索MEDLINE和Cancerlit，并补充来自注册库的信息、手工检索会议记录，以及与相关试验人员和组织进行讨论。这些检索工作定期更新至2004年9月。
旨在将经活检证实为浸润性（即临床分期为T2 - T4a）膀胱移行细胞癌的患者随机分组，接受有或无辅助化疗的局部确定性治疗的试验符合纳入标准。
我们收集、验证并重新分析了所有可用随机试验中所有随机分组患者的更新数据，包括来自6项随机对照试验的491例患者。对于所有结局指标，我们使用固定效应模型获得总体合并风险比。为了探讨试验设计的潜在影响，我们预先计划了按试验设计中可能影响治疗效果的重要方面对试验进行分组的分析。为了研究预定义患者亚组中效应的任何差异，我们对生存的主要终点进行了分层对数秩分析。
分析基于来自6项试验的491例患者，占基于顺铂的联合化疗试验中所有随机分组患者的90%，以及所有符合条件试验中患者的66%。该荟萃分析的效能明显有限。生存的总体风险比为0.75（95%CI 0.60 - 0.96，p = 0.019），表明与对照组相比，化疗使死亡风险相对降低了25%。Cox回归分析表明患者特征的微小不平衡不会使结果偏向化疗。然而，早期终止的试验、未接受分配治疗或未接受挽救性化疗的患者的影响尚不清楚。
这项个体患者数据荟萃分析提供了目前关于辅助化疗在浸润性膀胱癌中作用的最佳证据。然而，目前尚无足够证据可靠地为治疗决策提供依据。这些结果凸显了对辅助化疗应用进行进一步研究的迫切需求。在得出任何明确结论之前，需要如正在进行的EORTC - 30994试验等适当规模随机试验的结果。
