Liquid Biopsy Characterizing Circulating Tumor Cells Can Aid Treatment Selection

A liquid biopsy using phlebotomy blood samples can identify phenotypes and genomic characteristics of circulating tumor cells that may personalize treatment selection for men with advanced prostate cancer, according to the results of a study presented by Howard I. Scher, MD, Chief, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, NY, at the 2016 ASCO Genitourinary Cancers Symposium.

“Hormonal agents prolong the lives of men with castrate-resistant prostate cancer. The optimal sequence of agents to maximize survival is unknown. It is not known if a taxane would be more beneficial after an AR [androgen receptor]-directed therapy. We need biomarkers that can be used each time a treatment decision is needed,” explained Dr Scher.

Liquid Biopsy

The liquid biopsy was obtained from phlebotomy samples, and it characterized the heterogeneity of circulating tumor cells on a cell-by-cell basis at 3 key decision points, including before initiating treatment with enzalutamide (Xtandi), abiraterone acetate (Zytiga), or the taxane docetaxel (Taxotere).

The test was based on a phlebotomy blood sample that was stained with dye to identify circulating tumor cells and distinguish them from normal cells. The cells were scanned for morphologic features, “much like facial recognition software used at airports,” Dr Scher said.

A total of 15 mathematically defined circulating tumor cell phenotypes were identified. The frequency of these phenotypes differed by sample and by line of therapy. Heterogeneity was measured by the Shannon index score. Higher heterogeneity scores were seen with each subsequent line of therapy. The circulating tumor cells were also analyzed for genetic abnormalities.

Study Details

The study was based on 221 blood samples from 179 patients with castration-resistant prostate cancer who were about to undergo treatment with enzalutamide, abiraterone acetate, or docetaxel. A higher Shannon index score (ie, greater heterogeneity or diversity) was associated with a poor response to AR-directed therapy with enzalutamide or abiraterone acetate.

In patients treated with enzalutamide or abiraterone acetate, the median progression-free survival was 5 months for those with a high Shannon index score versus 17 months for those with a low Shannon index score. Overall survival was 9 months versus not yet being reached in the groups, respectively (P <.001). By contrast, no association was seen between the Shannon index score and the response to taxane therapy.

These results suggest that initiating therapy with a taxane in patients with a high Shannon index score could lead to a better outcome than starting with enzalutamide or with abiraterone acetate.

Isolated circulating tumor cells (741 cells isolated from 31 patients) were then analyzed for genotypic heterogeneity by gene amplification studies.

Type K circulating tumor cells had a large nucleus, high nuclear entropy, and frequent nucleoli, and was associated with poorer outcomes, but this finding needs further study, Dr Scher noted.

Personalized Medicine Tool

“Prostate cancer tumors change and become more complex over time, suggesting that the cancer cell has machinery to evade treatment. A test such as this would be of incredible value [if validated] and allow us to offer the right treatment to the right patient. This is a personalized selection tool,” said ASCO spokesperson Sumanta K. Pal, MD, Assistant Clinical Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, who moderated the presentation at the meeting.

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