Circulating Tumor Cells Predict Survival Benefit From Treatment In Metastatic Castration-Resistant Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 10 Nov 2008 - 4:00 PDT

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UroToday.com - In the October 1, 2008 issue of Clinical Cancer Research, Dr. Johann de Bono and colleagues presented exciting data indicating that circulating tumor cells (CTC) predict overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). CTC using the commercially available CellSearch is approved by the FDA as a prognostic indicator for patients with metastatic breast, prostate, and colorectal cancer. CTC have been reported to correlate with clinical outcomes in patients with CRPC.

The authors hypothesized that CTC enumeration pre-initiation and post-initiation of a new cytotoxic treatment could predict OS. A total of 65 clinical centers participated in the study. CTC measurement was performed after cell labeling, and CTC was defined as nucleated cells lacking CD45 and expressing cytokeratin. Numerous study data was collected and assessment of CTC and PSA were repeated before each course of cytotoxic therapy - until disease progression or up to 18 months. Patients were prospectively categorized as having either unfavorable (>5CTC/7.5ml) or favorable (<5CTC/7.5ml) CTC counts. The primary objective was to demonstrate that the median OS for patients with unfavorable counts 2 to 5 weeks after the initiation of a new line of chemotherapy was half the median OS of patients with favorable CTC counts at this same time point.

A total of 276 patients with CRPC were enrolled between October 2004 and February 2006. Of these, 45 were ineligible. At time of analysis, 119 of the 231 evaluable patients had died, resulting in a median OS of 17.2 months. At the time of analysis, 28 of 94 favorable patients (30%) and 83 of 125 unfavorable patients (66%) were alive with a median OS of 21.7 months and 11.5 months, respectively (p<0.0001).

The median OS of patients with favorable CTC at 2 to 5 weeks after treatment was 20.7 months, compared with 9.5 months for unfavorable patients (p<0.0001). In longer follow-up, the median OS differences between patients with favorable and unfavorable CTC at 6 to 8, 9 to 12, and 13 to 20 weeks after the initiation of therapy were similar to differences in OS at 2 to 5 weeks. In univariate and multivariate analysis, baseline and post-treatment CTC counts were highly prognostic and independent of the number of lines of cytotoxic chemotherapy and established prognostic markers. Some patients converted groups (from favorable to unfavorable or visa versa).

Those with continual unfavorable counts had the shortest median OS (6.8 months), compared to those who converted from unfavorable to favorable after treatment (median OS 21.3 months) and those who had favorable CTC counts throughout (median OS >26 months). Those converting from favorable to unfavorable after treatment had a median OS of 9.3 months. Compared to a PSA decline of either 30% or 50%, differences between favorable and unfavorable CTC counts were statistically significant after 6 to 8 weeks and most significant at 13 to 20 weeks. Furthermore, CTC counts 9 to 12 weeks after treatment had superior predictive power compared with post-treatment PSA changes to predict death within 12 months of the baseline blood draw.

de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D
Clin Cancer Res. 2008 Oct 1;14(19):6302-9.
doi:10.1158/1078-0432.CCR-08-0872

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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