Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer

Bono, Johann S. de; Scher, Howard I.; Montgomery, Robert B.; Parker, Christopher; Miller, Michael Craig; Tissing, H.; Doyle, Gerald V.; Terstappen, Leon W.M.M.; Pienta, Kenneth J.; Raghavan, Derek

doi:10.1158/1078-0432.ccr-08-0872

Cited by 1,989 publications

(1,711 citation statements)

References 25 publications

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“…Assessment of CTC using CellSearch has been cleared by the Food and Drug Administration as a prognostic indicator, in conjunction with other clinical methods, for patients with metastatic breast, prostate, and colorectal cancers. Studies in metastatic breast, colorectal, and prostate cancer showed that patients about to start new lines of chemotherapy could be divided into groups with favourable and unfavourable prognosis on the basis of the number of CTCs measured with the analytically valid CellSearch system(Veridex, Raritan, NJ, USA) [3,[5][6][7][8][9][10][11][12][13]20]. When studying the association between the number of CTCs and evolution of the disease, researchers generally use a single cutpoint to identify favorable and unfavorable response groups, such as 5 CTCs for MBC [3,4,14], three for metastatic colorectal cancer [11], and five for castration resistant prostate cancer [7].…”

Section: Discussionmentioning

confidence: 99%

“…Circulating tumor cells (CTCs) have been shown to be an independent prognostic factor in metastatic breast cancer (MBC) [3][4][5][6], in metastatic prostate cancer [7][8][9][10] and in metastatic colorectal cancer [11,12]. They represent a promising tool for therapeutic monitoring: an elevated number of CTCs measured at any time in the clinical course were associated with a high likelihood of a very short time to progression.…”

Section: Introductionmentioning

confidence: 99%

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Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Botteri

Sandri

Bagnardi

et al. 2009

Breast Cancer Res Treat

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Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2009, 122 (1), pp.211-217. <10.1007/s10549-009-0668-7>. EPIDEMIOLOGYModeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer Abstract Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (Pvalue \ 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Botteri

Sandri

Bagnardi

et al. 2009

Breast Cancer Res Treat

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“…[7][8][9][10][11][12][13][14] However, the magnitude of the benefit provided by each factor has varied among studies, and the value of these factors in predicting overall survival (OS) for Chinese patients is still unclear. In the present study, we retrospectively analysed the data from 115 mCRPC patients treated with docetaxel to explore the prognostic factors of survival outcomes in Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

Qu¹,

Dai²,

Kong³

et al. 2012

Asian J Androl

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This study aims to evaluate the potential value of patient characteristics in predicting overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time (PSADT), baseline haemoglobin (Hb) concentration, alkaline phosphatase (ALP) concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT ,46.3 days and baseline ALP o110 IU l 21 , all patients were divided into three risk groups: low-risk group (no risk factors), intermediate-risk group (one risk factor) and high-risk group (two risk factors). Median OSs for patients in low-, intermediate-and high-risk groups were 28.0 months (95% CI: 23.8-32.2), 21.0 months (95% CI: 18.9-23.1) and 11.0 months (95% CI: 7.6-14.4), respectively (P,0.001). In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

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“…Moreover, using the Food and Drug Administration's approved CellSearch platform, the CTC number is a prognostic biomarker in metastatic breast, prostate, and colorectal cancer patients. [7][8][9][10][11] The phenomenon of "partial" or "incomplete" EMT is also purported, in which metastasizing cells adopt some mesenchymal features (eg, expression of vimentin and neural cadherin) but retain some epithelial characteristics (eg, cytokeratin and membrane E-cadherin). 12 An alternative model for metastasis involving tumor cell co-operativity has also been postulated based on a rodent model that demonstrated mesenchymal cells provided invasive capability to allow "passenger" noninvasive epithelial cells access to the blood stream where they survived and were responsible for metastasis.…”

mentioning

confidence: 99%

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Hou

Krebs

Ward

et al. 2011

The American Journal of Pathology

392

369

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Circulating tumor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homo- Metastasis usually portends a dismal prognosis for cancer patients and effective therapeutic intervention in the metastatic process remains elusive. This is the case despite decades of research after Paget's "seed and soil" hypothesis in 1889 to explain why primary tumors within one particular organ give rise to secondary tumors at nonrandom sites 1 and Ewing's suggestion in 1929 that mechanical factors associated with the anatomy of human vasculature also determine the final destination of metastasizing tumor cells. 2 It is now apparent that tumor cell invasion and formation of distant metastasis can progress via three major routes: i) via the bloodstream, ii) via lymphatic vessels, and iii) via transcoelomic spread into the pleural, pericardial, and abdominal cavities. 3 The hematogenous system is thought to be the primary and most common route for the formation of distant metastases. Disseminating tumor cells can also circulate to and lie dormant in the bone marrow, potentially for a number of years, and then re-enter the bloodstream en route to secondary metastatic sites. 4 According to the widely espoused epithelial-to-mesenchymal transition (EMT) paradigm, suggested by some as essential for metastasis, 5,6 invading mesenchymal tumor cells lose cell-cell adhesion. Consistent with this concept, there are increasing reports enumerating individual circulating tumor cells (CTCs) in cancer patients' blood samples. Moreover, using the Food and Drug Administration's approved CellSearch platform, the CTC number is a prognostic biomarker in metastatic breast,

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Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer

Cited by 1,989 publications

References 25 publications

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

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