Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Urology, M. D. Anderson Cancer Center, Houston, Texas.
J Urol. 2018 Jun;199(6):1452-1458. doi: 10.1016/j.juro.2017.12.062. Epub 2018 Jan 9.
Level I evidence supports the usefulness of neoadjuvant cisplatin based chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced traditional MVAC, we compared pathological response and survival rates in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy with dose dense MVAC vs gemcitabine and cisplatin.
We retrospectively reviewed the records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total of 20 contributing institutions from 2000 to 2015. Patients with cT3-4aN0M0 disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less were compared between the gemcitabine and cisplatin, and dose dense MVAC regimens. Two multivariable Cox proportional hazards regression models of overall mortality were generated using preoperative and postoperative data.
Of the patients who underwent neoadjuvant chemotherapy and radical cystectomy during the study period 319 met our inclusion criteria. A significantly lower rate of ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The mean Kaplan-Meier estimates of overall survival in the gemcitabine and cisplatin, and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On multivariable cox regression analysis based on preoperative data patients who received gemcitabine and cisplatin were at higher risk for death than patients who received dose dense MVAC (HR 2.07, 95% CI 1.25-3.42, p = 0.003). Lymph node invasion (HR 1.97, 95% CI 1.15-3.36, p = 0.01) and hydronephrosis (HR 2.18, 95% CI 1.43-3.30, p <0.001) were also associated with higher risk of death.
In our retrospective cohort of patients with locally advanced bladder cancer dose dense MVAC was associated with higher complete pathological response and improved survival rates compared to gemcitabine and cisplatin. A clinical trial is warranted to validate these hypothesis generating results to test the superiority of neoadjuvant dose dense MVAC in patients with locally advanced bladder cancer.
I 级证据支持新辅助顺铂为基础的化疗对肌层浸润性膀胱癌的有效性。由于剂量密集型 MVAC（甲氨蝶呤、长春碱、多柔比星和顺铂）已基本取代传统 MVAC，我们比较了接受新辅助化疗的局部晚期膀胱癌患者接受剂量密集型 MVAC 与吉西他滨和顺铂治疗的病理反应和生存率。
我们回顾性分析了 2000 年至 2015 年期间在 20 个合作机构接受新辅助化疗和膀胱切除术的尿路上皮癌患者的记录。选择 cT3-4aN0M0 疾病患者进行这项分析。比较吉西他滨和顺铂与剂量密集型 MVAC 方案的 ypT0N0 和 ypT1N0 或更低的比率。使用术前和术后数据生成了两个总体死亡率的多变量 Cox 比例风险回归模型。
在研究期间接受新辅助化疗和根治性膀胱切除术的患者中，有 319 名符合我们的纳入标准。吉西他滨和顺铂组 ypT0N0 的比例明显低于剂量密集型 MVAC 组（14.6%对 28.0%，p=0.005）。吉西他滨和顺铂组 ypT1N0 或更低的比例为 30.1%，而剂量密集型 MVAC 组为 41.0%（p=0.07）。吉西他滨和顺铂组和剂量密集型 MVAC 组的平均 Kaplan-Meier 总生存估计分别为 4.2 年和 7.0 年（p=0.001）。基于术前数据的多变量 Cox 回归分析显示，接受吉西他滨和顺铂治疗的患者死亡风险高于接受剂量密集型 MVAC 治疗的患者（HR 2.07，95%CI 1.25-3.42，p=0.003）。淋巴结侵犯（HR 1.97，95%CI 1.15-3.36，p=0.01）和肾积水（HR 2.18，95%CI 1.43-3.30，p<0.001）也与死亡风险增加相关。
在我们回顾性的局部晚期膀胱癌患者队列中，与吉西他滨和顺铂相比，剂量密集型 MVAC 与更高的完全病理缓解率和生存率改善相关。需要进行临床试验来验证这些产生假设的结果，以测试局部晚期膀胱癌患者新辅助剂量密集型 MVAC 的优越性。
