Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder: Association with tumor stage, lymph node metastases, FDG-PET findings, and survival

Johan Abrahamsson*, Kristina Aaltonen, Helgi Engilbertsson, Fredrik Liedberg, Oliver Patschan, Lisa Rydén, Gottfrid Sjödahl, Sigurdur Gudjonsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells. Objective To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer. Design, setting, and participants Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients. Outcome measurements and statistical analysis Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival. Results CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6–21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005–7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM. Conclusions CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen–based CTC detection methods.

Original languageEnglish
Pages (from-to)606.e9-606.e16
JournalUrologic Oncology: Seminars and Original Investigations
Volume35
Issue number10
DOIs
Publication statusPublished - Oct 2017

Bibliographical note

Funding Information:
This research was supported by grants from the Swedish Cancer Society (CAN 2014/448), Hillevi Fries Research Fund, G?sta J?nsson Research Fund, Gunnar Nilsson Research Fund, Sk?ne University Hospital Research Funds, Maud and Birger Gustavsson Research Fund, and Lund University Medical Faculty Foundation, Sweden (ALF).

Publisher Copyright:
© 2017 Elsevier Inc.

Other keywords

  • Bladder cancer
  • Circulating tumor cells
  • EpCAM
  • FDG-PET-CT
  • Urothelial carcinoma of the bladder

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