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

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.

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%).

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).

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.

Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954.

ESMO open. 2022 Mar 02 [Epub ahead of print]

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 Sleijfer, J L Boormans

Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: ., Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Department of Urology, Maasstad Hospital, Rotterdam, The Netherlands., Department of Urology, Zuyderland Medical Center, Heerlen, The Netherlands., Department of Urology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands., Department of Urology, Isala Hospital, Zwolle, The Netherlands., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Urology, Maxima MC, Eindhoven, The Netherlands., Department of Urology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands., Department of Urology, Reinier de Graaf Gasthuis, Delft, The Netherlands., Department of Urology, St. Antonius Hospital, Nieuwegein, The Netherlands., Department of Urology, Rijnstate Hospital, Arnhem, The Netherlands., Department of Urology, Bravis Hospital, Roosendaal, The Netherlands.

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