Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer

Lauren E. Howard, Daniel Moreira, Amanda De Hoedt, William J. Aronson, Christopher J. Kane, Christopher Amling, Matthew R. Cooperberg, Martha K. Terris, Stephen J. Freedland

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). Materials and Methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

Original languageEnglish (US)
JournalBJU International
DOIs
StateAccepted/In press - 2017

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Castration
Prostate-Specific Antigen
Prostatic Neoplasms
Mortality
Neoplasm Metastasis
Veterans Hospitals
Proportional Hazards Models

Keywords

  • #ProstateCancer
  • Castration-resistant prostate cancer
  • Metastasis
  • PSA doubling time
  • Risk stratification

ASJC Scopus subject areas

  • Urology

Cite this

Howard, L. E., Moreira, D., De Hoedt, A., Aronson, W. J., Kane, C. J., Amling, C., ... Freedland, S. J. (Accepted/In press). Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU International. https://doi.org/10.1111/bju.13856

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. / Howard, Lauren E.; Moreira, Daniel; De Hoedt, Amanda; Aronson, William J.; Kane, Christopher J.; Amling, Christopher; Cooperberg, Matthew R.; Terris, Martha K.; Freedland, Stephen J.

In: BJU International, 2017.

Research output: Contribution to journalArticle

Howard, LE, Moreira, D, De Hoedt, A, Aronson, WJ, Kane, CJ, Amling, C, Cooperberg, MR, Terris, MK & Freedland, SJ 2017, 'Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer', BJU International. https://doi.org/10.1111/bju.13856
Howard, Lauren E. ; Moreira, Daniel ; De Hoedt, Amanda ; Aronson, William J. ; Kane, Christopher J. ; Amling, Christopher ; Cooperberg, Matthew R. ; Terris, Martha K. ; Freedland, Stephen J. / Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. In: BJU International. 2017.
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title = "Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer",
abstract = "Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). Materials and Methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95{\%} CI 5.07-14.7) and PCSM (HR 9.29, 95{\%} CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95{\%} CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.",
keywords = "#ProstateCancer, Castration-resistant prostate cancer, Metastasis, PSA doubling time, Risk stratification",
author = "Howard, {Lauren E.} and Daniel Moreira and {De Hoedt}, Amanda and Aronson, {William J.} and Kane, {Christopher J.} and Christopher Amling and Cooperberg, {Matthew R.} and Terris, {Martha K.} and Freedland, {Stephen J.}",
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T1 - Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer

AU - Howard, Lauren E.

AU - Moreira, Daniel

AU - De Hoedt, Amanda

AU - Aronson, William J.

AU - Kane, Christopher J.

AU - Amling, Christopher

AU - Cooperberg, Matthew R.

AU - Terris, Martha K.

AU - Freedland, Stephen J.

PY - 2017

Y1 - 2017

N2 - Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). Materials and Methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

AB - Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). Materials and Methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

KW - #ProstateCancer

KW - Castration-resistant prostate cancer

KW - Metastasis

KW - PSA doubling time

KW - Risk stratification

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