February 2016, Vol. 5, No. 1

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Liquid Biopsy Characterizing CTCs Can Aid in Treatment Selection

Howard Scher, MD

Genitourinary Cancers Symposium

Howard,Scher98pxA “liquid biopsy” using phlebotomy blood samples can identify phenotypes and genomic characteristics of circulating tumor cells (CTCs) that may help personalize treatment selection for men with advanced prostate cancer.

“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 androgen receptor-directed therapy. We need biomarkers that can be used each time a treatment decision is needed,” explained Howard Scher, MD, Chief, Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center, New York City.

The liquid biopsy was obtained from phlebotomy samples and characterized the heterogeneity of CTCs on a cell-by-cell basis at 3 key decision points—before initiating treatment with enzalutamide, abiraterone acetate, or docetaxel (taxane).

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

Fifteen mathematically defined CTC phenotypes were identified. The frequency of these phenotypes differed by sample and line of therapy. Heterogeneity was measured by the Shannon Index score. Higher heterogeneity scores were seen with each subsequent line of therapy. The CTCs were also analyzed for genetic abnormalities.

The study was based on 221 blood samples from 179 patients with castrate-resistant prostate cancer 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 androgen receptor–directed therapy with enzalutamide or abiraterone acetate.

In patients treated with enzalutamide or abiraterone acetate, 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 reached, respectively (P <.0001).

No association was seen between Shannon Index score and 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 using either enzalutamide or abiraterone acetate.

Isolated CTCs (n = 741 cells isolated from 31 patients) were then analyzed for genotypic heterogeneity by gene amplification studies. “Type K” had a large nucleus, high nuclear entropy, and frequent nucleoli and was associated with poorer outcomes, but this finding needs further study, Scher said.

Comment on Study

“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 Sumanta Pal, MD, ASCO spokesperson and moderator of a press conference where this research was featured. Pal is a medical oncologist at City of Hope in Duarte, CA.

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