Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG) 94-08

Bret Verhoven, Yan Yan, Mark Ritter, Li Yan Khor, Elizabeth Hammond, Christopher Jones, Mahul Amin, Jean Paul Bahary, Kenneth Zeitzer, Alan Pollack

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number2
DOIs
StatePublished - Jun 1 2013

Fingerprint

Radiation Oncology
mortality
International System of Units
metastasis
radiation therapy
Prostatic Neoplasms
Radiotherapy
cancer
deprivation
Neoplasm Metastasis
Androgens
Mortality
hazards
causes
predictions
stratification
Recurrence
quartiles
Random Allocation
staining

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG) 94-08. / Verhoven, Bret; Yan, Yan; Ritter, Mark; Khor, Li Yan; Hammond, Elizabeth; Jones, Christopher; Amin, Mahul; Bahary, Jean Paul; Zeitzer, Kenneth; Pollack, Alan.

In: International Journal of Radiation Oncology Biology Physics, Vol. 86, No. 2, 01.06.2013, p. 317-323.

Research output: Contribution to journalArticle

Verhoven, Bret ; Yan, Yan ; Ritter, Mark ; Khor, Li Yan ; Hammond, Elizabeth ; Jones, Christopher ; Amin, Mahul ; Bahary, Jean Paul ; Zeitzer, Kenneth ; Pollack, Alan. / Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG) 94-08. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 86, No. 2. pp. 317-323.
@article{96b85ca10a30426cbefc7c715da53177,
title = "Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG) 94-08",
abstract = "Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6{\%}) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.",
author = "Bret Verhoven and Yan Yan and Mark Ritter and Khor, {Li Yan} and Elizabeth Hammond and Christopher Jones and Mahul Amin and Bahary, {Jean Paul} and Kenneth Zeitzer and Alan Pollack",
year = "2013",
month = "6",
day = "1",
doi = "10.1016/j.ijrobp.2013.01.016",
language = "English (US)",
volume = "86",
pages = "317--323",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG) 94-08

AU - Verhoven, Bret

AU - Yan, Yan

AU - Ritter, Mark

AU - Khor, Li Yan

AU - Hammond, Elizabeth

AU - Jones, Christopher

AU - Amin, Mahul

AU - Bahary, Jean Paul

AU - Zeitzer, Kenneth

AU - Pollack, Alan

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

AB - Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

UR - http://www.scopus.com/inward/record.url?scp=84877585402&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877585402&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2013.01.016

DO - 10.1016/j.ijrobp.2013.01.016

M3 - Article

C2 - 23474109

AN - SCOPUS:84877585402

VL - 86

SP - 317

EP - 323

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 2

ER -