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

• Published in: ESMO open 2022-04, Vol.7 (2), p.100416-100416, Article 100416
• Main Authors: Beije, N., de Kruijff, I.E., de Jong, J.J., Klaver, S.O., de Vries, P., Jacobs, R.A.L., Somford, D.M., te Slaa, E., van der Heijden, A.G., Alfred Witjes, J., Fossion, L.M.C.L., Boevé, E.R., van der Hoeven, J., van Melick, H.H.E., Wijburg, C.J., Bickerstaffe, H., Martens, J.W.M., de Wit, R., Kraan, J., Sleijfer, S., Boormans, J.L.
• Format: Article
• Language: English
• Subjects: Aged; circulating tumour cells; CTCs; Female; Humans; liquid biopsy; Male; muscle-invasive bladder cancer; Muscles - pathology; neoadjuvant chemotherapy; Neoadjuvant Therapy; Neoplastic Cells, Circulating; Original Research; Recurrence; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100416

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 •Two-year OS in CTC-negative MIBC patients did not meet the criterion for trial success.•CTCs are prognostic for cancer-related mortality and relapse-free survival in MIBC.•CTC-positive MIBC patients survived longer when receiving NAC in explorative analyses.•The absence of CTCs alone is insufficient to withhold NAC in MIBC patients.