BERKELEY, CA (UroToday.com) - While recent genomic signature-based diagnostics have improved our ability to determine which prostate cancer patients are at an increased risk for recurrence and development of metastases, we are still unable to provide adequate prediction for a large subset of patients. With such uncertainty, many patients opt for otherwise unnecessary intervention, with all the potential patient risks and costs to the health care system that entails. We hypothesized that analysis of circulating tumor cells (CTCs) could add to our ability to predict which patients would relapse, and therefore which would benefit most from interventional therapy.
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CTCs are cells that are shed into the bloodstream from primary or metastatic tumors and in metastatic prostate and other cancers; CTCs identified by the CellSearch platform have been shown to be prognostic for overall survival (OS). We thought that identification of CTCs in patients diagnosed with localized prostate cancer might portend the eventual occurrence of metastases. Therefore, we initiated a proof-of-concept clinical trial in men with ‘high-risk’ localized prostate cancer, those who would be more likely to have CTCs. Earlier reports suggested that few, if any, CTCs could be found in the localized cancer setting, so we adapted methodology originated by the scientists at Veridex to isolate CTCs from the buffy coat of 30mls of blood instead of directly from 7.5mls of blood. Using this method, we were able to detect CTCs in about half of the patient samples. Unfortunately, we were unable to detect high numbers of CTCs, which made correlative analyses difficult. Because CTC fragments had previously been shown to correlate with OS in metastatic prostate cancer just like intact CTCs, we were able to use CTC fragments for correlative analyses.
It likely isn’t simply the presence of CTCs that will correlate with development of metastases, because gaining the ability to invade through the basal membrane into a blood or lymphatic vessel and gaining the ability to colonize a metastatic site are two independent events. It is likely that a particular subset of CTCs is responsible for the development of metastases. We hypothesized that CTCs with features of stem cells or epithelial-mesenchymal transition would have greater metastatic potential. Indeed, it did appear that expression of the putative stem cell marker CD133 on CTC fragments might portend a worse outcome. A larger follow-up study will be necessary to test this possibility.
Such a trial may not be advisable with the current CellSearch platform because of its limited sensitivity. However, new CTC enumeration and isolation technologies are rapidly being developed. Several platforms are more sensitive and provide the opportunity to define a greater number of markers. Once these platforms are validated in clinical trials similar to those used for the validation of the CellSearch platform, they could be used in a trial to determine if CTCs can add to our ability to predict recurrence and development of metastases in localized prostate cancer patients.
Jeremy Jones, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Assistant Professor, Cancer Biology Beckman Research Institute, City of Hope, Duarte, CA USA