Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer

Karim Fizazi, Christophe Massard, Matthew Smith, Michael Rader, Janet Brown, Piotr Milecki, Neal Shore, Stephane Oudard, Lawrence Karsh, Michael A Carducci, Ronaldo Damiaõ, Huei Wang, Wendy Ying, Carsten Goessl

Research output: Contribution to journalArticle

Abstract

Background: Previous studies have reported on prognostic factors for castrationresistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≥143 U/l ( p <0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p <0.0001); corrected urinary N-telopeptide (uNTx) ≥50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory- Short Form [BPI-SF] score ≥4) (p <0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p <0.0001); and longer time from first bone metastasis to randomization (p <0.0001). Other significant predictors of improved survival included prostatespecific antigen (PSA) level <10 ng/ml (p <0.0001), hemoglobin >128 g/l (p <0.0001), absence of visceral metastases (p <0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalEuropean Urology
Volume68
Issue number1
DOIs
StatePublished - 2015

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Castration
Prostatic Neoplasms
Neoplasm Metastasis
Bone and Bones
Survival
Nomograms
docetaxel
L-Lactate Dehydrogenase
Proportional Hazards Models
Alkaline Phosphatase
Outcome Assessment (Health Care)
Confidence Intervals
Drug Therapy

Keywords

  • Bone metastases
  • Castration-resistant prostate cancer
  • Nomogram
  • Prognostic factors
  • Survival

ASJC Scopus subject areas

  • Urology

Cite this

Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer. / Fizazi, Karim; Massard, Christophe; Smith, Matthew; Rader, Michael; Brown, Janet; Milecki, Piotr; Shore, Neal; Oudard, Stephane; Karsh, Lawrence; Carducci, Michael A; Damiaõ, Ronaldo; Wang, Huei; Ying, Wendy; Goessl, Carsten.

In: European Urology, Vol. 68, No. 1, 2015, p. 42-50.

Research output: Contribution to journalArticle

Fizazi, K, Massard, C, Smith, M, Rader, M, Brown, J, Milecki, P, Shore, N, Oudard, S, Karsh, L, Carducci, MA, Damiaõ, R, Wang, H, Ying, W & Goessl, C 2015, 'Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer', European Urology, vol. 68, no. 1, pp. 42-50. https://doi.org/10.1016/j.eururo.2014.10.001
Fizazi, Karim ; Massard, Christophe ; Smith, Matthew ; Rader, Michael ; Brown, Janet ; Milecki, Piotr ; Shore, Neal ; Oudard, Stephane ; Karsh, Lawrence ; Carducci, Michael A ; Damiaõ, Ronaldo ; Wang, Huei ; Ying, Wendy ; Goessl, Carsten. / Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer. In: European Urology. 2015 ; Vol. 68, No. 1. pp. 42-50.
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T1 - Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer

AU - Fizazi, Karim

AU - Massard, Christophe

AU - Smith, Matthew

AU - Rader, Michael

AU - Brown, Janet

AU - Milecki, Piotr

AU - Shore, Neal

AU - Oudard, Stephane

AU - Karsh, Lawrence

AU - Carducci, Michael A

AU - Damiaõ, Ronaldo

AU - Wang, Huei

AU - Ying, Wendy

AU - Goessl, Carsten

PY - 2015

Y1 - 2015

N2 - Background: Previous studies have reported on prognostic factors for castrationresistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≥143 U/l ( p <0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p <0.0001); corrected urinary N-telopeptide (uNTx) ≥50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory- Short Form [BPI-SF] score ≥4) (p <0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p <0.0001); and longer time from first bone metastasis to randomization (p <0.0001). Other significant predictors of improved survival included prostatespecific antigen (PSA) level <10 ng/ml (p <0.0001), hemoglobin >128 g/l (p <0.0001), absence of visceral metastases (p <0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

AB - Background: Previous studies have reported on prognostic factors for castrationresistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≥143 U/l ( p <0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p <0.0001); corrected urinary N-telopeptide (uNTx) ≥50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory- Short Form [BPI-SF] score ≥4) (p <0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p <0.0001); and longer time from first bone metastasis to randomization (p <0.0001). Other significant predictors of improved survival included prostatespecific antigen (PSA) level <10 ng/ml (p <0.0001), hemoglobin >128 g/l (p <0.0001), absence of visceral metastases (p <0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KW - Bone metastases

KW - Castration-resistant prostate cancer

KW - Nomogram

KW - Prognostic factors

KW - Survival

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