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

N. Beije*, I. E. de Kruijff, J. J. de Jong, S. O. Klaver, P. de Vries, R. A.L. Jacobs, D. M. Somford, E. te Slaa, A. G. van der Heijden, J. Alfred Witjes, L. M.C.L. Fossion, E. R. Boevé, J. van der Hoeven, H. H.E. van Melick, C. J. Wijburg, H. Bickerstaffe, J. W.M. Martens, R. de Wit, J. Kraan, S. SleijferJ. L. Boormans

*Corresponding author for this work

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Abstract

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. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC. Trial registration: Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954

Original languageEnglish
Article number100416
JournalESMO Open
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Apr 2022

Bibliographical note

Funding Information:
This work was supported by an Erasmus MC Research Grant (no grant number) and Cancer Genomics Netherlands (no grant number). JWMM and SS report a research agreement with Menarini, unrelated to the currently submitted manuscript. JLB reports consultancy work for MSD, Janssen, ISMAR Health Care, Eight Medical, BMS and AMBU (all paid to the Erasmus MC) and a research agreement with Decipher. All other authors declare no conflict of interest.

Funding Information:
This work was supported by an Erasmus MC Research Grant (no grant number) and Cancer Genomics Netherlands (no grant number).

Publisher Copyright:
© 2022 The Author(s)

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