EAU 2017: Circulating Tumor Cells in Prostate Cancer: A Marker?

London, England (UroToday.com) In this session, biomarker monitoring of prostate cancer and its treatment were discussed. Importantly, there are difference in the cell mutation profile depending on the phase of disease. In late prostate cancer, for example, most metastatic cells are similar to the primary tumor. However, in early phase disease, many metastatic deposits are dissimilar from the primary tumor. This speaks towards marked tumor heterogeneity in the evolutionary history of prostate cancer. Metastases have large genetic diversity, which occurs by linear and branching patterns of spread (Gudem et al., Nature 2015). Nonetheless, these genetic differences may have large implications for treatment choices and response to treatment.

One major problem with getting this information is limited ability to garner tissue. Tissue is rarely obtained at the time of clinical decision-making. Further, if it is obtained, accessible tissue may not be completely representative of the tumor.

Circulating tumor cells (CTCs), on the other hand are readily accessible as they are shed by both primary and metastatic tumor cells. They convey real-time information about current disease state. Further, molecular pathway profiling in CTCs can be used for patient selection to stratify patients for targeted therapy or other proper systemic treatments.

CTC analysis has been shifting from enumerations to molecular characterization. Various methods are being used to find CTCs. Most commonly, the epithelial cellular adhesion molecule called EpCAM is targeted. A disadvantage of this strategy is that we only capture CTCs that express EpCAM. Other platforms such as EPIC and Pasortex make use of other antibodies and size, respectively, and may provide more actionable information.

Clinically speaking, most studies considering utility have been done in metastatic prostate cancer with high volume disease. Here, the number of CTCs in the blood stream can predict prognosis, and patients with < 5 CTCs have better survival outcomes than those with > 5CTCs. Furthermore, receiver operating characteristics curve demonstrates improved survival prognostication than PSA in these patients.

One of the most important distinctions available through CTC analysis is the presence of AR-V7 splice variants. Typically, AR-V7 variants emerge during AR-Targeted therapy and predict treatment resistance. For example, patients with few AR-V7 splice variants do much better on abiraterone or enzalutamide relative to high AR-V7. However, AR-V7 has little impact in patients on taxanes.

A natural question stemming from these explorations of CTCs in the metastatic seeting is whether we can extrapolate to localized and recurrent disease. To date, CTCs have been noted in these patients, but they fail to correlate with PSA levels, pT stage, gleason score, or BCR-free survival.

In summary, CTC analysis has promise to identify and stratify appropriate treatment recommendations in metastatic prostate cancer, but is not likely helpful in the localized setting.

Presented by: S. Osanto

Written by: Benjamin T. Ristau, MD, SUO Fellow, Fox Chase Cancer Center, Philadelphia, PA

at the #EAU17 -March 24-28, 2017- London, England

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