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

Abrahamsson, Johan LU ; Aaltonen, Kristina LU ; Engilbertsson, Helgi LU ; Liedberg, Fredrik LU ; Patschan, Oliver LU ; Rydén, Lisa LU ; Sjödahl, Gottfrid LU and Gudjonsson, Sigurdur LU (2017) In Urologic Oncology
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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Bladder cancer, Circulating tumor cells, EpCAM, FDG-PET-CT, Urothelial carcinoma of the bladder
in
Urologic Oncology
publisher
Elsevier
external identifiers
  • scopus:85021403985
ISSN
1078-1439
DOI
10.1016/j.urolonc.2017.05.021
language
English
LU publication?
yes
id
ee97e228-54bb-41e5-a598-ab619b231a87
date added to LUP
2017-08-22 09:37:59
date last changed
2017-08-23 03:00:07
@article{ee97e228-54bb-41e5-a598-ab619b231a87,
  abstract     = {<p>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.</p>},
  author       = {Abrahamsson, Johan and Aaltonen, Kristina and Engilbertsson, Helgi and Liedberg, Fredrik and Patschan, Oliver and Rydén, Lisa and Sjödahl, Gottfrid and Gudjonsson, Sigurdur},
  issn         = {1078-1439},
  keyword      = {Bladder cancer,Circulating tumor cells,EpCAM,FDG-PET-CT,Urothelial carcinoma of the bladder},
  language     = {eng},
  month        = {07},
  publisher    = {Elsevier},
  series       = {Urologic Oncology},
  title        = {Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder : Association with tumor stage, lymph node metastases, FDG-PET findings, and survival},
  url          = {http://dx.doi.org/10.1016/j.urolonc.2017.05.021},
  year         = {2017},
}