Circulating Tumor Cell Number and Prognosis in Progressive Castration-Resistant Prostate Cancer

Abstract

Purpose: The development of tumor-specific markers to select targeted therapies and to assess clinical outcome remains a significant area of unmet need. We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies. Experimental Design: CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood from 120 patients with progressive clinical castrate metastatic disease. We estimated the probability of survival over time by the Kaplan-Meier method. The concordance probability estimate was used to gauge the discriminatory strength of the informative prognostic factors. Results: Sixty-nine (57%) patients had five or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were observed in patients with bone metastases relative to those with soft tissue disease and in patients who had received prior cytotoxic chemotherapy relative to those who had not. CTC counts were modestly correlated to measurements of tumor burden such as prostate-specific antigen and bone scan index, reflecting the percentage of boney skeleton involved with tumor. Baseline CTC number was strongly associated with survival, without a threshold effect, which increased further when baseline prostate-specific antigen and albumin were included. Conclusions: Baseline CTC was predictive of survival, with no threshold effect. The shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease, and provides unique information relative to prognosis.

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

“…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].…”

“…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.…”

Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

“…This suggests that AA interacts with adipogenic differentiation pathways, inducing a proportional increase in adipocyte numbers. Thus, in the presence of specific lipids, the number of BM-Ad will increase, potentially augmenting the chemoattractive stimulus of migrating cancer cells known to be in circulation in escalating numbers as cancer load increases (Danila et al, 2007) and increasing the statistical chance of 'proximity' encounters between migrating cancer cells and BM-Ad. Thus, in a 'Darwinian' sense, the 'fitness' of the cancer cell to survive and propagate in red BM is enhanced.…”

Phase II trial of Belagenpumatucel-L, a TGF-β2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients

“…Correlation with survival, using the Veridex technology, has been demonstrated in breast cancer 15,16 colorectal cancer 31 and castration resistant prostate cancer. 32 Animal studies have shown a correlation between the number of CTC's and the number of lung metastases and tumor burden 33 although this has not been confirmed in cancer patients where, in at least one study, a correlation between radiographic tumor volume and CTC's was not found. 34 If, with further studies, the number of CTC's proves not to be correlated with either the number of metastatic sites or the cumulative tumor burden, then other potential biological correlates will need to be explored including, but not limited to, adhesiveness, vascular permeability, and immune mediated interactions with both macroscopic tumor and circulating tumor cells.…”