Pathologic Downstaging Is a Surrogate Marker for Efficacy and Increased Survival Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Urothelial Bladder Cancer

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• 作者：Robert Rosenblatt^a ; ^&dagger ; ; Amir Sherif^b ; ^&dagger ; ; ^{amir.sherif-abdel-hadi@karolinska.se} ; ^{amir.m.sherif@gmail.com} ; Erkki Rintala^c ; Rolf Wahlqvist^d ; Anders Ullé ; n^e ; Sten Nilsson^e ; Per-Uno Malmströ ; m^f ; the Nordic Urothelial Cancer Group
• 关键词：Urinary bladder neoplasms ; Neoadjuvant therapy
• 刊名：European Urology
• 出版年：2012
• 期刊代码：289_03022838
• 类别：med
• 出版时间：June, 2012
• 卷：61
• 期：6
• 页码：1229-1238
• 文件大小：1779 K

摘要

Background

Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer.

Objective

To assess the effect of NAC on tumour downstaging and overall survival.

Design, setting, and participants

A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2-T4aNXM0 preoperatively and pT0-pT4aN0鈭扤 + M0 postoperatively. The median follow-up time was 5 yr.

Intervention

The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only.

Measurements

The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (鈮T3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC.

Results and limitations

Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1%in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging.

Conclusions

Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.