Issue: June 25, 2014
April 03, 2014
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Increased circulating tumor cells predicted shorter OS in prostate cancer

Issue: June 25, 2014
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Higher circulating tumor cell count at baseline and an increasing count thereafter were associated with shorter OS among men with metastatic, castration-resistant prostate cancer treated with first-line docetaxel, according to a subanalysis of a phase 3 trial.

The analysis included men enrolled in the SWOG S0421 trial who were treated with docetaxel plus atrasentan (AbbVie) or docetaxel alone. Researcher evaluated samples at baseline and before the start of the second treatment cycle (day 21).

Overall, the median baseline circulating tumor cell count was five cells per 7.5 mL. Circulating tumor cell counts of at least five were associated with worse bone pain, higher PSA, more liver disease, lower hemoglobin and higher alkaline phosphatase.

A significantly higher percentage of patients with a median baseline circulating tumor cell count of fewer than five cells per 7.5 mL achieved PSA response than those with at least five cells per 7.5 mL (63% vs. 44%; P=.01).

Patients with fewer than five circulating tumor cells per 7.5 mL also experienced longer median OS (26 months vs. 13 months; HR=2.74; 95% CI, 1.72-4.37).

Researchers noted the area under the curve of receiver operator characteristic curves was higher for circulating tumor cells than for PSA at baseline. Results of integrated discrimination improvement analyses indicated adding day-0 circulating tumor cell data to PSA and other covariates resulted in an 8% to 10% increase in survival prognosis accuracy.

An increase in circulating tumor cell count from baseline to day 21 was associated with shorter OS (HR=2.55; P=.041).

Although circulating tumor cell counts are only prognostic of survival outcomes and not treatment responses, future research may improve their value, Terence W. Friedlander, MD, and Lawrence Fong, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California at San Francisco, wrote in an accompanying editorial.

“Circulating tumor cells are entirely different from almost all other biomarkers because they represent a sampling of a patient’s tumor,” Friedlander and Fong wrote. “The molecular and genomic profiling of circulating tumor cells may therefore identify novel mutations, shed light on mechanisms of resistance to therapy, and aid in the selection of appropriate therapies in real time. Thus, although the analysis by Goldkorn et al is not practice changing, it again shows that circulating tumor cells can tell us, in a limited way, about prognosis. If we ask the right questions going forward, circulating tumor cells may be able to tell us much more.”

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Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.