Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes

Results from the SEARCH database

Christopher J. Keto, William J. Aronson, Martha Kennedy Terris, Joseph C. Presti, Christopher J. Kane, Christopher L. Amling, Stephen J. Freedland

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.

Original languageEnglish (US)
Pages (from-to)620-627
Number of pages8
JournalEuropean Urology
Volume65
Issue number3
DOIs
StatePublished - Mar 1 2014

Fingerprint

Prostate-Specific Antigen
Androgens
Prostatic Neoplasms
Databases
Therapeutics
Prostatectomy
Castration
Neoplasm Metastasis
Mortality
Proportional Hazards Models

Keywords

  • Androgen-deprivation therapy
  • Prostate cancer
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Urology

Cite this

Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes : Results from the SEARCH database. / Keto, Christopher J.; Aronson, William J.; Terris, Martha Kennedy; Presti, Joseph C.; Kane, Christopher J.; Amling, Christopher L.; Freedland, Stephen J.

In: European Urology, Vol. 65, No. 3, 01.03.2014, p. 620-627.

Research output: Contribution to journalArticle

Keto, Christopher J. ; Aronson, William J. ; Terris, Martha Kennedy ; Presti, Joseph C. ; Kane, Christopher J. ; Amling, Christopher L. ; Freedland, Stephen J. / Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes : Results from the SEARCH database. In: European Urology. 2014 ; Vol. 65, No. 3. pp. 620-627.
@article{8a8f0c6fe0aa4c0fadd179deb651034a,
title = "Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes: Results from the SEARCH database",
abstract = "Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76{\%}) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.",
keywords = "Androgen-deprivation therapy, Prostate cancer, Prostate-specific antigen",
author = "Keto, {Christopher J.} and Aronson, {William J.} and Terris, {Martha Kennedy} and Presti, {Joseph C.} and Kane, {Christopher J.} and Amling, {Christopher L.} and Freedland, {Stephen J.}",
year = "2014",
month = "3",
day = "1",
doi = "10.1016/j.eururo.2012.11.052",
language = "English (US)",
volume = "65",
pages = "620--627",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes

T2 - Results from the SEARCH database

AU - Keto, Christopher J.

AU - Aronson, William J.

AU - Terris, Martha Kennedy

AU - Presti, Joseph C.

AU - Kane, Christopher J.

AU - Amling, Christopher L.

AU - Freedland, Stephen J.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.

AB - Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.

KW - Androgen-deprivation therapy

KW - Prostate cancer

KW - Prostate-specific antigen

UR - http://www.scopus.com/inward/record.url?scp=84895061392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895061392&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2012.11.052

DO - 10.1016/j.eururo.2012.11.052

M3 - Article

VL - 65

SP - 620

EP - 627

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 3

ER -