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

Goldkorn, Amir and Ely, Benjamin and Tangen, Catherine M. and Tai, Yu-Chong and Xu, Tong and Liu, Hongli and Twardowski, Przemyslaw and Van Velhuizen, Peter J. and Agarwal, Neeraj and Carducci, Michael A. and Monk, J. Paul, III and Garzotto, Mark and Mack, Philip C. and Lara, Primo, Jr. and Higano, Celestia S. and Hussain, Maha and Vogelzang, Nicholas J. and Thompson, Ian M., Jr. and Cote, Richard J. and Quinn, David I. (2015) Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial. International Journal of Cancer, 136 (8). pp. 1856-1862. ISSN 0020-7136. PMCID PMC4323674.

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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.

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Tai, Yu-Chong0000-0001-8529-106X
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
Funding AgencyGrant Number
National Cancer InstituteCA32102
National Cancer InstituteCA38926
National Cancer InstituteCA46368
National Cancer InstituteCA46441
National Cancer InstituteCA58882
National Cancer InstituteCA58861
National Cancer InstituteCA12644
National Cancer InstituteCA22433
National Cancer InstituteCA46282
National Cancer InstituteCA27057
National Cancer InstituteCA58416
National Cancer InstituteCA45807
National Cancer InstituteCA45808
National Cancer InstituteCA45450
National Cancer InstituteCA42777
National Cancer InstituteCA35281
National Cancer InstituteCA20319
National Cancer InstituteCA35090
National Cancer InstituteCA76429
National Cancer InstituteCA14028
National Cancer InstituteCA67575
National Cancer InstituteCA35377
National Cancer InstituteCA68183
National Cancer InstituteCA63848
National Cancer InstituteCA74647
National Cancer InstituteCA16385
National Cancer InstituteCA35192
National Cancer InstituteCA63844
National Cancer InstituteCA11083
National Cancer InstituteCA63845
National Cancer InstituteCA76447
National Cancer InstituteCA35128
National Cancer InstituteCA13612
National Cancer InstituteCA35431
National Cancer InstituteCA76448
National Cancer InstituteCA35178
National Cancer InstituteCA35176
National Cancer InstituteCA35119
National Cancer InstituteCA35421
National Cancer InstituteCA128567
National Cancer InstituteCA04919
National Cancer InstituteCA68183
National Cancer InstituteCA45560
National Cancer InstituteCA37981
National Cancer InstituteCA58723
National Cancer InstituteCA21115
National Cancer InstituteCA31946
National Cancer InstituteCA16116
National Cancer InstituteCA31949
National Cancer InstituteCA014089-38
Canadian Cancer Society Research Institute (CCSR)I015469
Hope FoundationCA141077
Abbott LaboratoriesUNSPECIFIED
Subject Keywords:circulating tumor cells, telomerase activity, prostate cancer, prognosis, biomarker
Issue or Number:8
PubMed Central ID:PMC4323674
Record Number:CaltechAUTHORS:20150327-064036652
Persistent URL:
Official Citation:Goldkorn, A., Ely, B., Tangen, C. M., Tai, Y.-C., Xu, T., Li, H., Twardowski, P., Veldhuizen, P. J. V., Agarwal, N., Carducci, M. A., Monk, J. P., Garzotto, M., Mack, P. C., Lara, P., Higano, C. S., Hussain, M., Vogelzang, N. J., Thompson, I. M., Cote, R. J. and Quinn, D. I. (2015), Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial. Int. J. Cancer, 136: 1856–1862. doi: 10.1002/ijc.29212
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56154
Deposited By: Ruth Sustaita
Deposited On:27 Mar 2015 16:44
Last Modified:03 Oct 2019 08:11

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