Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy

Prognostic value of a time-and-PSA threshold model

Sean X. Cavanaugh, Patrick A. Kupelian, Clifton D. Fuller, Chandana Reddy, Patrick Bradshaw, Bradley H Pollock, Martin Fuss

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

BACKGROUND. The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma. METHODS. The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up. RESULTS. During a median follow-up of 74 months (range, 24-189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained BRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001). CONCLUSIONS. Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and-PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and-PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace.

Original languageEnglish (US)
Pages (from-to)96-105
Number of pages10
JournalCancer
Volume101
Issue number1
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

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Prostate-Specific Antigen
Prostate
Radiotherapy
Carcinoma

Keywords

  • Biochemical recurrence-free survival
  • Outcome
  • Prognostic factor
  • Prostate carcinoma
  • Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy : Prognostic value of a time-and-PSA threshold model. / Cavanaugh, Sean X.; Kupelian, Patrick A.; Fuller, Clifton D.; Reddy, Chandana; Bradshaw, Patrick; Pollock, Bradley H; Fuss, Martin.

In: Cancer, Vol. 101, No. 1, 01.07.2004, p. 96-105.

Research output: Contribution to journalReview article

Cavanaugh, Sean X. ; Kupelian, Patrick A. ; Fuller, Clifton D. ; Reddy, Chandana ; Bradshaw, Patrick ; Pollock, Bradley H ; Fuss, Martin. / Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy : Prognostic value of a time-and-PSA threshold model. In: Cancer. 2004 ; Vol. 101, No. 1. pp. 96-105.
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title = "Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy: Prognostic value of a time-and-PSA threshold model",
abstract = "BACKGROUND. The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma. METHODS. The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up. RESULTS. During a median follow-up of 74 months (range, 24-189 months), 540 patients (64.4{\%}) maintained bRFS, whereas 299 patients (35.6{\%}) did not maintain bRFS. The median nadir among patients with sustained BRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001). CONCLUSIONS. Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and-PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and-PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace.",
keywords = "Biochemical recurrence-free survival, Outcome, Prognostic factor, Prostate carcinoma, Radiotherapy",
author = "Cavanaugh, {Sean X.} and Kupelian, {Patrick A.} and Fuller, {Clifton D.} and Chandana Reddy and Patrick Bradshaw and Pollock, {Bradley H} and Martin Fuss",
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T1 - Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy

T2 - Prognostic value of a time-and-PSA threshold model

AU - Cavanaugh, Sean X.

AU - Kupelian, Patrick A.

AU - Fuller, Clifton D.

AU - Reddy, Chandana

AU - Bradshaw, Patrick

AU - Pollock, Bradley H

AU - Fuss, Martin

PY - 2004/7/1

Y1 - 2004/7/1

N2 - BACKGROUND. The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma. METHODS. The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up. RESULTS. During a median follow-up of 74 months (range, 24-189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained BRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001). CONCLUSIONS. Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and-PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and-PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace.

AB - BACKGROUND. The goal of the current study was to analyze the prognostic value of early prostate-specific antigen (PSA) kinetics, with PSA assessed as reaching or failing to reach discrete threshold values at fixed time points during follow-up after external-beam radiotherapy (EBRT) for prostate carcinoma. METHODS. The authors conducted a retrospective review of PSA follow-up for 839 patients treated between May 1987 and December 2000 at the Cleveland Clinic Foundation (Cleveland, OH). They also assessed the impact on bRFS of PSA levels lower than defined threshold values at given time points during follow-up. RESULTS. During a median follow-up of 74 months (range, 24-189 months), 540 patients (64.4%) maintained bRFS, whereas 299 patients (35.6%) did not maintain bRFS. The median nadir among patients with sustained BRFS was 0.4 ng/mL, with a median time to nadir of 28.9 months. Patients who did not maintain bRFS reached a median nadir of 1.3 ng/mL at a median of 15 months (P < 0.0001 for both nadir level and time to nadir). Reaching PSA thresholds of 3.0, 2.0, 1.0, 0.5, and 0.2 ng/mL at any time during follow-up was correlated with improved bRFS (P < 0.0001, each threshold). Patients whose PSA levels crossed the appropriate thresholds within 3 and 6 months of follow-up, irrespective of the time or level of eventual nadir, exhibited significantly improved bRFS when compared with patients whose PSA levels reached those thresholds at any time during follow-up and patients whose PSA levels never reached those thresholds (all thresholds: P < 0.0001). CONCLUSIONS. Despite previous conclusions that early PSA assessment may lack prognostic value, the data obtained in the current study suggest that the kinetics of early PSA decline is predictive of long-term bRFS when assessed using a time-and-PSA threshold model. After EBRT for prostate carcinoma, PSA levels below various discrete PSA thresholds were indicative of statistically meaningful long-term outcome differences between experimental arms as early as 90 days after radiotherapy. If the time-and-PSA threshold model is shown to be predictive of prostate carcinoma mortality as well, then it may allow the scientific community to evaluate promising treatment concepts and technologies at a highly accelerated pace.

KW - Biochemical recurrence-free survival

KW - Outcome

KW - Prognostic factor

KW - Prostate carcinoma

KW - Radiotherapy

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DO - 10.1002/cncr.20328

M3 - Review article

VL - 101

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