- CTCs can be measured in blood, which is easy, cheap, have relatively little pain and risks associated with them.
- CTCs can be used as a biomarker; once isolated, viable CTCs can be processed and analyzed to identify:
- the type of CTC in circulation
- aggressiveness of the cancer
- potential response to specific treatments (like chemotherapy)
- CTCs can be measured over time, adding a new dimension to the ability to measure resistance or responsiveness to therapies.
CTCs as a BiomarkerThrough a variety of techniques, prostate cancer CTCs have been analyzed for a variety of markers that can define the aggressiveness of the prostate cancer and have the potential to predict clinical outcomes. These markers encompass a number of established protein and genetic markers of prostate cancer aggressiveness including: chromosomal abnormalities, epidermal growth factor receptor (EGFR) expression, androgen receptor (AR) gene amplification, telomerase activity and TMPRSS2-ERG status.[1-6]
CTCs as Predictors of Oncologic OutcomesHigh CTC counts are associated with more advanced disease including higher PSA levels, bone metastases (compared to soft tissue metastases), volume of bone metastases by imaging and laboratory markers (lactate dehydrogenase and alkaline phosphatase).[7,8]
High CTC counts predict men who develop castrate-resistant prostate cancer, and the relative length of survival and response to chemotherapy for men who have already developed castrate-resistant prostate cancer.[7-10] In one study of men receiving chemotherapy for metastatic, castrate-resistant prostate cancer, low CTC counts (<5) were associated with a longer survival prior to initiating chemotherapy. In the same study and others, men who's CTC counts dropped to <5 while on additional therapy also had a longer survival compared to men who had no response in CTC count.[9-11]
The best cutoff value for CTC has yet to be established, with most studies reporting the clinically important cutoff to be between 3-5 CTC.[8,9]
CTCs have demonstrated prognostic abilities in hormone-sensitive disease, in mCRPC treated with a variety of first-line therapies,[9,11] and in mCRPC treated with second-line hormonal therapy.
A recent, large, prospectively phase III trial was completed by SWOG (Southwest Oncology Group) evaluating CTCs in men with metastatic, castrate-resistant prostate cancer receiving docetaxel chemotherapy (standard first-line chemotherapy). This study validated 5 CTC as a valuable cut-point in this population as men with <5 CTCs at enrollment had an improved overall survival (26 vs. 13 months) and that a rising CTC count while on chemotherapy was associated with worse overall survival.
- CTCs have the opportunity to change the way we manage advanced prostate cancer and other malignancies.
- CTCs can serve as biomarkers to indicate the aggressiveness of prostate cancer cells.
- Increasing CTC counts are associated with worse oncologic outcomes in a number of trials for men with advanced prostate cancer - however the exact cutoff point for CTCs has yet to be determined.
- Future studies will help define the role of CTCs in prostate cancer.
 Shaffer DR, Leversha MA, Danila DC, et al. (2007) Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res 13:2023–2029.
 Goodman OB Jr, Symanowski JT, Loudyi A, et al. (2011) Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer 9:31–38.
 Scher HI, Heller G, Molina A, et al. (2011) Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): Planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel. J Clin Oncol 29(suppl):293s, abstr LBA4517.