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Published April 15, 2015 | public
Journal Article Open

Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial


Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p = 0.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6–54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p = 0.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step towards molecular CTC-based precision cancer management.

Additional Information

© 2014 UICC. Received 21 May 2014; Accepted 15 Aug 2014; Online 13 Sep 2014. Article first published online: 8 Oct 2014. C.S.H.: Potential personal COI: Husband founded CTI Bio Pharma; Potential financial COI: Abbott (Abbvie) and Sanofi-Aventis (honorarium/travel); Research funding from Sanofi, Amgen, Aragon, AstraZeneca, Dendreon, Genentech, Medivation, Millennium, Teva Pharmaceuticals. M.H.: Potential personal COI: PI on CTEP-sponsored trial using ABT888. A.G.: Potential personal COI: Co-inventor of patent jointly held by University of Southern California and Caltech for the microfilter used in the experiments described in this article. D.I.Q.: Potential personal COI: Scientific advisory board participation and honoraria from Jannsen, Astellas, Bayer, Dendreon, Genentech, Medivation and Novartis; Research funding from Millennium-Takeda. R.J.C.: Potential personal COI: One of the inventors of microfilters used in this study to capture circulating tumors cells (CTC). Potential financial COI: Equity owner in Filtini, Inc., licensee of the intellectual property company used in this study. Y.-C.T.: Potential financial COI: Co-inventor of U.S. Patent 7,846,393. This study uses filters described in this U.S. patent Grant sponsors: PHS Cooperative Agreement grants by the National Cancer Institute at the National Institutes of Health and DHHS; Grant numbers: CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433, CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844, CA11083, CA63845, CA76447, CA35128, CA13612, CA35431, CA76448, CA35178, CA35176, CA35119, CA35421, CA128567, CA04919, CA68183, CA45560, CA37981, CA58723, CA21115, CA31946, CA16116, CA31949, CA014089-38, CCSRI 015469 and CA141077; Grant sponsors: Hope Foundation and Abbott Laboratories and Sanofi-Aventis

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Supplemental Material - ijc29212-sup-0002-suppinfotab02.docx


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August 20, 2023
August 20, 2023