A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel

Kim N Chi, T Kheoh, Charles James Ryan, Arturo Molina, Joaquim Bellmunt, Nicholas J Vogelzang, Dana E Rathkopf, Karim Fizazi, Philip W Kantoff, Jun Li, Arun A Azad, Bernhard J Eigl, Daniel Y C Heng, Anthony M Joshua, Johann S De Bono, Howard I Scher

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Abstract

Background Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. Patients and methods Baseline data were available from 762 patients treated with abiraterone–prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. Results Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286). Conclusion This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. Trial registration numbers NCT00638690.
Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number3
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • castration-resistant prostate cancer
  • abiraterone acetate
  • prognostic
  • risk
  • survival

Cite this

Chi, Kim N ; Kheoh, T ; Ryan, Charles James ; Molina, Arturo ; Bellmunt, Joaquim ; Vogelzang, Nicholas J ; Rathkopf, Dana E ; Fizazi, Karim ; Kantoff, Philip W ; Li, Jun ; Azad, Arun A ; Eigl, Bernhard J ; Heng, Daniel Y C ; Joshua, Anthony M ; De Bono, Johann S ; Scher, Howard I. / A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. In: Annals of Oncology. 2016 ; Vol. 27, No. 3. pp. 454-460.
@article{b483612b8acd4ac5945fff66b039d1fa,
title = "A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel",
abstract = "Background Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. Patients and methods Baseline data were available from 762 patients treated with abiraterone–prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. Results Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46{\%}), intermediate (n = 321, 40{\%}) and poor (n = 107, 13{\%}) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286). Conclusion This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. Trial registration numbers NCT00638690.",
keywords = "castration-resistant prostate cancer, abiraterone acetate, prognostic, risk, survival",
author = "Chi, {Kim N} and T Kheoh and Ryan, {Charles James} and Arturo Molina and Joaquim Bellmunt and Vogelzang, {Nicholas J} and Rathkopf, {Dana E} and Karim Fizazi and Kantoff, {Philip W} and Jun Li and Azad, {Arun A} and Eigl, {Bernhard J} and Heng, {Daniel Y C} and Joshua, {Anthony M} and {De Bono}, {Johann S} and Scher, {Howard I}",
year = "2016",
doi = "10.1093/annonc/mdv594",
language = "English",
volume = "27",
pages = "454--460",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
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Chi, KN, Kheoh, T, Ryan, CJ, Molina, A, Bellmunt, J, Vogelzang, NJ, Rathkopf, DE, Fizazi, K, Kantoff, PW, Li, J, Azad, AA, Eigl, BJ, Heng, DYC, Joshua, AM, De Bono, JS & Scher, HI 2016, 'A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel' Annals of Oncology, vol. 27, no. 3, pp. 454-460. https://doi.org/10.1093/annonc/mdv594

A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. / Chi, Kim N; Kheoh, T; Ryan, Charles James; Molina, Arturo; Bellmunt, Joaquim; Vogelzang, Nicholas J; Rathkopf, Dana E; Fizazi, Karim; Kantoff, Philip W; Li, Jun; Azad, Arun A; Eigl, Bernhard J; Heng, Daniel Y C; Joshua, Anthony M; De Bono, Johann S; Scher, Howard I.

In: Annals of Oncology, Vol. 27, No. 3, 2016, p. 454-460.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel

AU - Chi, Kim N

AU - Kheoh, T

AU - Ryan, Charles James

AU - Molina, Arturo

AU - Bellmunt, Joaquim

AU - Vogelzang, Nicholas J

AU - Rathkopf, Dana E

AU - Fizazi, Karim

AU - Kantoff, Philip W

AU - Li, Jun

AU - Azad, Arun A

AU - Eigl, Bernhard J

AU - Heng, Daniel Y C

AU - Joshua, Anthony M

AU - De Bono, Johann S

AU - Scher, Howard I

PY - 2016

Y1 - 2016

N2 - Background Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. Patients and methods Baseline data were available from 762 patients treated with abiraterone–prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. Results Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286). Conclusion This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. Trial registration numbers NCT00638690.

AB - Background Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC. Patients and methods Baseline data were available from 762 patients treated with abiraterone–prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort. Results Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286). Conclusion This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design. Trial registration numbers NCT00638690.

KW - castration-resistant prostate cancer

KW - abiraterone acetate

KW - prognostic

KW - risk

KW - survival

UR - http://annonc.oxfordjournals.org/content/early/2015/12/17/annonc.mdv594.full.pdf+html

U2 - 10.1093/annonc/mdv594

DO - 10.1093/annonc/mdv594

M3 - Article

VL - 27

SP - 454

EP - 460

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -