Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer

Amir Goldkorn, Benjamin Ely, David I. Quinn, Catherine M. Tangen, Louis M. Fink, Tong Xu, Przemyslaw Twardowski, Peter J. Van Veldhuizen, Neeraj Agarwal, Michael A. Carducci, J. Paul Monk, Ram Datar, Mark Garzotto, Philip C. Mack, Primo Lara, Celestia S. Higano, Maha Hussain, Ian Murchie Thompson, Richard J Cote, Nicholas J. Vogelzang

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Purpose: Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods: CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results: Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion: These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

Original languageEnglish
Pages (from-to)1136-1142
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number11
DOIs
StatePublished - Apr 10 2014

Fingerprint

docetaxel
bis(2,3,3,3-tetrachloropropyl) ether
Circulating Neoplastic Cells
Castration
Prostate-Specific Antigen
Prostatic Neoplasms
Cell Count
Survival
Prednisone
Area Under Curve
Alkaline Phosphatase
atrasentan
Liver Diseases
Hemoglobins
Regression Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Circulating tumor cell counts are prognostic of overall survival in SWOG S0421 : A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. / Goldkorn, Amir; Ely, Benjamin; Quinn, David I.; Tangen, Catherine M.; Fink, Louis M.; Xu, Tong; Twardowski, Przemyslaw; Van Veldhuizen, Peter J.; Agarwal, Neeraj; Carducci, Michael A.; Monk, J. Paul; Datar, Ram; Garzotto, Mark; Mack, Philip C.; Lara, Primo; Higano, Celestia S.; Hussain, Maha; Thompson, Ian Murchie; Cote, Richard J; Vogelzang, Nicholas J.

In: Journal of Clinical Oncology, Vol. 32, No. 11, 10.04.2014, p. 1136-1142.

Research output: Contribution to journalArticle

Goldkorn, A, Ely, B, Quinn, DI, Tangen, CM, Fink, LM, Xu, T, Twardowski, P, Van Veldhuizen, PJ, Agarwal, N, Carducci, MA, Monk, JP, Datar, R, Garzotto, M, Mack, PC, Lara, P, Higano, CS, Hussain, M, Thompson, IM, Cote, RJ & Vogelzang, NJ 2014, 'Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer', Journal of Clinical Oncology, vol. 32, no. 11, pp. 1136-1142. https://doi.org/10.1200/JCO.2013.51.7417
Goldkorn, Amir ; Ely, Benjamin ; Quinn, David I. ; Tangen, Catherine M. ; Fink, Louis M. ; Xu, Tong ; Twardowski, Przemyslaw ; Van Veldhuizen, Peter J. ; Agarwal, Neeraj ; Carducci, Michael A. ; Monk, J. Paul ; Datar, Ram ; Garzotto, Mark ; Mack, Philip C. ; Lara, Primo ; Higano, Celestia S. ; Hussain, Maha ; Thompson, Ian Murchie ; Cote, Richard J ; Vogelzang, Nicholas J. / Circulating tumor cell counts are prognostic of overall survival in SWOG S0421 : A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 11. pp. 1136-1142.
@article{40c1a274b1bc4d1cb7789e2308bdb29c,
title = "Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer",
abstract = "Purpose: Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods: CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results: Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8{\%} to 10{\%}. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion: These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.",
author = "Amir Goldkorn and Benjamin Ely and Quinn, {David I.} and Tangen, {Catherine M.} and Fink, {Louis M.} and Tong Xu and Przemyslaw Twardowski and {Van Veldhuizen}, {Peter J.} and Neeraj Agarwal and Carducci, {Michael A.} and Monk, {J. Paul} and Ram Datar and Mark Garzotto and Mack, {Philip C.} and Primo Lara and Higano, {Celestia S.} and Maha Hussain and Thompson, {Ian Murchie} and Cote, {Richard J} and Vogelzang, {Nicholas J.}",
year = "2014",
month = "4",
day = "10",
doi = "10.1200/JCO.2013.51.7417",
language = "English",
volume = "32",
pages = "1136--1142",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "11",

}

TY - JOUR

T1 - Circulating tumor cell counts are prognostic of overall survival in SWOG S0421

T2 - A phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer

AU - Goldkorn, Amir

AU - Ely, Benjamin

AU - Quinn, David I.

AU - Tangen, Catherine M.

AU - Fink, Louis M.

AU - Xu, Tong

AU - Twardowski, Przemyslaw

AU - Van Veldhuizen, Peter J.

AU - Agarwal, Neeraj

AU - Carducci, Michael A.

AU - Monk, J. Paul

AU - Datar, Ram

AU - Garzotto, Mark

AU - Mack, Philip C.

AU - Lara, Primo

AU - Higano, Celestia S.

AU - Hussain, Maha

AU - Thompson, Ian Murchie

AU - Cote, Richard J

AU - Vogelzang, Nicholas J.

PY - 2014/4/10

Y1 - 2014/4/10

N2 - Purpose: Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods: CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results: Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion: These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

AB - Purpose: Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods: CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results: Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion: These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

UR - http://www.scopus.com/inward/record.url?scp=84901951930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901951930&partnerID=8YFLogxK

U2 - 10.1200/JCO.2013.51.7417

DO - 10.1200/JCO.2013.51.7417

M3 - Article

C2 - 24616308

AN - SCOPUS:84901951930

VL - 32

SP - 1136

EP - 1142

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 11

ER -