Johan Abrahamsson1, Kristina Aaltonen2, Helgi Engilbertsson3, Fredrik Liedberg3, Oliver Patschan3, Lisa Rydén4, Gottfrid Sjödahl3, Sigurdur Gudjonsson5. 1. Department of Urology, Skåne University Hospital, Lund, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden. Electronic address: Johan.F.Abrahamsson@skane.se. 2. Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. 3. Department of Urology, Skåne University Hospital, Lund, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden. 4. Department of Surgery, Skåne University Hospital, Lund, Sweden; Division of Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden. 5. Department of Urology, Landspitali University Hospital, Reykjavik, Iceland.
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.
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.
Authors: Panagiotis J Vlachostergios; Christopher D Jakubowski; Muhammad J Niaz; Aileen Lee; Charlene Thomas; Amy L Hackett; Priyanka Patel; Naureen Rashid; Scott T Tagawa Journal: Bladder Cancer Date: 2018-07-30