Better prediction tools to predict treatment outcome in men with metastatic castration-resistant prostate cancer (mCRPC) should significantly improve treatment outcomes. Without good predictive measures we often don’t know when is the optimum time to stop a therapy and move to another. This means that we might maturely stop an effective treatment losing the effectiveness of the treatment. On the other hand without good measures we might continue a treatment which is not effective and allow the prostate cancer to flourish and grow stronger.
A new study from Dr. Otakar Apoun, of the Department of Urology at General Teaching Hospital Charles University in Prague, Czech Republic shows that in the prediction of a change in circulating tumour cells maybe be more accurate measure of a treatment than the change in prostate-specific antigen levels (PSA), the commonly used measure. The findings of this study were presented at the recent EAU 13th Central European Meeting in Prague.
“The research of the circulating tumour cells (CTC) is of utmost importance, because nowadays there is no reliable marker of both cancer-specific or overall survival in castration-resistant prostate cancer (CRPC) patients,” explained the lead author of the study. We also said that “The goal of this study is to assess the possibility of the individualisation of castration-resistant prostate cancer management. In cases with no favourable change in CTC detection during chemotherapy, the early switching to another therapy should be considered.”
The study involved the collection of peripheral blood from men with metastatic CRPC prior to docetaxel therapy and after the fourth cycle of chemotherapy (CTX). Circulating tumour cells were detected by using a method of immunomagnetic separation. In the course of the study multiplex-PCR was performed after cytolysis of CTC and the expression of tumour-associated antigens (PSA, PSMA and EGFR) was quantified.
The methodology of the study was based on verbal evaluation together with a report of the absolute values (ng/ml). The authors recorded the levels of serum PSA (sPSA) and the fragments of respective antigens before and in the course of CTX and compared the values. They also evaluated the correlation between the change of sPSA and expression of CTC antigens during CTX.
The study, which was small, included 26 men with both samples taken in 17. Median age was 72 years (54-82), mean sPSA level before and after CTX was 197.6 and 120.1ng/ml, respectively. Before CTX only 2 out of 26 patients were considered CTC negative, whereas during the CTX the CTC negativity was confirmed in 9 out of 17 cases.
Before CTX, positive detection of fragments of antigens for PSA, PSMA and EGFR was confirmed in 23, 16 and 2 patients, respectively, and during CTX in 8, 3 and 1 case, respectively. The sPSA level before CTX was associated with the level of fragments for PSA (p=0.0020) and PSMA (p=00.0147). During CTX the association was seen in all antigens. However neither a change in sPSA level nor a change in positive versus negative CTC statement correlated with a change of any of the tested antigens.
The study concludes that the sPSA level has the most accurate correlation with the level of gene fragment for PSA in CTC. A favourable change in CTC quantity will occur in more than a half of men during chemotherapy, however the change in CTC detection does not correlate with the change of the sPSA level.
“This research project is divided into several arms, among others, we are investigating the feasibility of CTC cultivation and genetic profiling,” commented Apoun referring to the possibility of follow-up research.
“This gene profile will be compared with primary tumour at the time of diagnosis. In the future, this CTC profiling might be useful for even more accurate and better tailored selection of treatment for castration-resistant prostate cancer.”
This is an area in great need for additional research. It offers us the possibility to better develop prognostic tools that will lead to more effective treatment protocols.
If you are interested in supporting additional, valuable research in the use of CTCs in advanced prostate cancer go to Malecare’s project, Start A Cure (www.StartACure.com) which is currently developing funding support for research at UCLA on CTCs in advanced prostate cancer.
Joel T. Nowak, M.A., M.S.W.