Circulating tumour cells to drive the use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer

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N. Beije¹  I.E. de Kruijff¹  J.J. de Jong²  S.O. Klaver³  P. de Vries⁴  R.A.L. Jacobs⁴  D.M. Somford⁵  E. te Slaa⁶  A.G. van der Heijden⁷  J. Alfred Witjes⁷  L.M.C.L. Fossion⁸  E.R. Boevé⁸  J. van der Hoeven⁸  H.H.E. van Melick⁹  C.J. Wijburg^1,10  H. Bickerstaffe^1,11  J.W.M. Martens¹  R. de Wit¹  J. Kraan¹  S. Sleijfer¹  J.L. Boormans² 

[1] Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center;Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center;Department of Urology, Maasstad Hospital;Department of Urology, Zuyderland Medical Center;Department of Urology, Canisius-Wilhelmina Hospital;Department of Urology, Isala Hospital;Department of Urology, Radboud University Medical Center;Department of Urology;Department of Urology, St. Antonius Hospital;Department of Urology, Rijnstate Hospital;Department of Urology, Bravis Hospital

关键词: circulating tumour cells;    neoadjuvant chemotherapy;    muscle-invasive bladder cancer;    CTCs;    liquid biopsy;   

DOI  :  10.1016/j.esmoop.2022.100416

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld.Patients and methods The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%).Results A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48).Conclusion The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC.

【 授权许可】

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