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UROSCAN
Year : 2012  |  Volume : 28  |  Issue : 3  |  Page : 371-372
 

Can detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma determine prognosis?


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Date of Web Publication19-Oct-2012

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How to cite this article:
Mandal S. Can detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma determine prognosis?. Indian J Urol 2012;28:371-2

How to cite this URL:
Mandal S. Can detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma determine prognosis?. Indian J Urol [serial online] 2012 [cited 2019 Sep 15];28:371-2. Available from: http://www.indianjurol.com/text.asp?2012/28/3/371/102736

Flaig TW, Wilson S, Bokhoven AV, Varella-Garcia M, Wolfe P, Maroni P, et al. Detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma. Urology. 2011 Oct;78(4):863-7.



   Summary Top


The presence of circulating tumor cells (CTCs) has been known since long but their role in routine clinical decision making has recently been realized due to wide availability of commercial products for its detection. The presence of significant levels of CTCs has been inversely associated with progression-free and overall survival. [1] In addition, isolated cells can be used to assess for the presence of tumor-specific targets of therapy. It has also been demonstrated that the serial assessment of CTCs gives ongoing information about an individual patient's response to therapy. [2] Although the existence of CTCs in patients with bladder cancer has previously been reported with the detection of epithelial markers in the peripheral circulation using reverse transcriptase-polymerase chain reaction, [3] few reports have used the newer method of immunomagnetic capture of CTCs in patients with urothelial cancer (UC).

Forty-four patients with either localized, muscle-invasive or metastatic UC were included in the study. Blood samples (7.5 mL) were collected from the patients and baseline CTC levels were obtained using the CellSearch System (Veridex, Raritan, NJ). It uses magnetic isolation of CTC from peripheral blood by identifying epithelial cell adhesion molecule. The CTCs were isolated and analyzed using a standard protocol. Cells identified as CTCs by immunomagnetic separation were validated by FISH analysis to demonstrate a chromosomal aneusomy, which is consistent with neoplastic transformation in UC.

Of the 44 subjects, detectable CTCs were observed in 12 (27%) patients. Of the 14 with metastatic disease, 7 (50%) had detectable CTCs (range 1-177) and 5 (36%) had ≥5 CTCs in the blood sample. Of the 28 preoperative subjects, all with clinically localized UC, 5 (18%) had detectable CTCs (range 1-6) and only 1 had ≥5 CTCs in the sample. Neither of the two postoperative subjects had detectable CTCs.

The survival of subjects was assessed according to the CTC status. All patients (n = 7) with metastatic UC and detectable CTCs died. In contrast, only 3 (43%) of 7 patients with metastatic UC and without CTCs died during the same period. The median survival time of metastatic UC was 156 versus 337 days for the detectable and undetectable groups, respectively. Of the patients with metastatic UC, 5 had ≥5 CTCs, and the CTC level was followed up every 2 months during chemotherapy until they had decreased to ≤5. The two patients with the greatest CTC levels (99 and 177) had rapidly progressive disease and died before their first reassessment point. Two other patients with a baseline CTC level of 27 and 34 did not have any detectable CTCs at the 2-month reassessment point. Thus, the survival analysis for the patients with metastatic disease suggests a prognostic role of CTCs.


   Comments Top


The immunomagnetic assessment method of CTCs is currently used for several cancer types, including breast, [2] colon, [4] and prostate cancer. [1] The results of the present trial have demonstrated that CTCs are frequently detected in patients with UC and metastatic disease using a commercially available assay.

The role of the CTC as a preoperative marker has been assessed in a limited manner in bladder cancer. In the study by Rink et al, [5] out of 50 preoperative patients with clinically localized, bladder cancer, CTCs were detected in 15 (30%) patients, while the present study has demonstrated CTCs in 5 (18%) of 28 preoperative patients with UC. Taken together, these findings suggest that CTCs can be observed frequently enough to merit additional study of CTCs as a risk stratifying factor in the preoperative setting for patients with UC scheduled to undergo radical cystectomy, and future neoadjuvant treatment studies should incorporate CTC into their design. Considering the significant "targetable" markers in bladder cancer and the need to assess new biologic therapies for UC, the assessment of CTCs in UC is a promising method to increase the speed of therapeutic development in this area. Larger cohorts of patients with UC are needed to better define a meaningful CTC level in terms of the clinical outcome; however, the data from the present study suggest that even the identification of a single CTC could be meaningful. The data presented in the study are hypothesis generating, and future metastatic bladder cancer studies should be designed to incorporate CTC enumeration as both a prognostic and a predictive marker.

 
   References Top

1.de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration- resistant prostate cancer. Clin Cancer Res 2008;14:6302-9.  Back to cited text no. 1
    
2.Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 2006;12:4218-24.  Back to cited text no. 2
    
3.Osman I, Kang M, Lee A, Deng FM, Polsky D, Mikhail M, et al. Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor inbladder cancer patients. Int J Cancer 2004;111:934-9.  Back to cited text no. 3
    
4.Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:3213-21.  Back to cited text no. 4
    
5.Rink M, Chun FK, Minner S, Friedrich M, Mauermann O, Heinzer H, et al. Detection of circulating tumour cells in peripheral blood of patients with advanced non-metastaticbladder cancer. BJU Int 2011;107:1668-75.  Back to cited text no. 5
    




 

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