Knowns and Unknowns in the Clinical Application of CTC Testing for Prostate Cancer

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Cancer Therapy Advisor asked Dr David Graham (left) and Dr Alexander Kutikov (right) about the state of the science of circulating tumor cell testing in prostate cancer, as well as this emerging field
Cancer Therapy Advisor asked Dr David Graham (left) and Dr Alexander Kutikov (right) about the state of the science of circulating tumor cell testing in prostate cancer, as well as this emerging field

David Graham, MD, FASCO, is an American Society of Clinical Oncology (ASCO) expert and a physician-administrator at the Levine Cancer Institute of the Carolinas HealthCare System in Charlotte, North Carolina. An expert in genitourinary cancers, including prostate cancer, hematologic malignancies, and neuroendocrine tumors, Dr Graham serves on ASCO's Cancer Communications Committee and the Practice Guidelines Implementation Network (PGIN).

Alexander Kutikov, MD, FACS, is professor and chief of urologic oncology in the department of surgical oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania. Dr Kutikov is an expert in prostate, kidney, bladder, ureteral, testicular, and penile cancer.

Cancer Therapy Advisor asked Dr David Graham and Dr Alexander Kutikov about the state of the science of circulating tumor cell testing in prostate cancer, as well as this emerging field's potential clinical applications.

Dr Graham

Cancer Therapy Advisor: Are CTC tests likely to become diagnostic tools in prostate cancer — or do early-stage tumors shed too few CTCs for reliable detection?

Dr Graham: As the technology stands today, it is unlikely that CTCs will become a diagnostic tool. Beyond conforming a malignant diagnosis, the role of the prostate biopsy is to gauge the aggressiveness of the disease. The pattern of cell growth in the prostate gland itself is of prime importance in this. We do not get that information from CTCs.

Cancer Therapy Advisor: What are the most near-term clinical applications of CTC testing? (Identifying aggressive genomics or phenotypes? Monitoring tumor evolution and the emergence of drug resistance? Predicting or detecting metastasis?)

Dr Graham: Right now, there can be a few roles for CTC testing. We can use CTCs to identify the AR-V7 variant of the androgen receptor. This variant has a very poor response rate to abiraterone and enzalutamide. There are also data suggesting that treatment leading to CTC levels dropping from more than 5 to fewer than 5 or even dropping to zero can be a good prognostic indicator.

Cancer Therapy Advisor: What is the best CTC capture technology — or is there a clearly superior technology? Are cross-platform CTC tests a realistic goal?

Dr Graham: I do not wish to comment on technology comparisons.

Cancer Therapy Advisor: Many assays rely on CTC enumeration — counting tumor cells. But what are the emerging roles of phenotypic or morphologic — or genomic — analyses in CTC testing? 

Dr Graham: Detecting the AR-V7 variant of the androgen receptor can be clinically useful. Something that is hypothesized is that the AR-V7 variant may develop or be selected for with the use of abiraterone or enzalutamide.

[… T]he use of abiraterone or enzalutamide after the other has a fairly poor response rate. Subsequent treatment with docetaxel may diminish that clone. If the AR-V7 variant were seen before use of docetaxel and disappears after docetaxel, we may have a new window to use the other agent.

Cancer Therapy Advisor: What about the timing of CTC sampling? Is it ‘one size fits all' or should timing vary with the intensity of treatment or the stage or aggressiveness of a patient's cancer?

Dr Graham: This is all still be worked out. There is no set algorithm to the timing of these studies. They can be expensive so it would not be likely that they are frequently checked.

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