Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group trial 92-02

Alan Pollack, M. Desilvio, L. Y. Khor, R. Li, T. I. Al-Saleem, M. E. Hammond, V. Venkatesan, C. A. Lawton, M. Roach, W. U. Shipley, G. E. Hanks, H. M. Sandler

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Purpose: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT)-treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001 ), CSD (P < .0001 ), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

Original languageEnglish
Pages (from-to)2133-2140
Number of pages8
JournalJournal of Clinical Oncology
Volume22
Issue number11
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Radiation Oncology
Androgens
Prostatic Neoplasms
Radiotherapy
Staining and Labeling
Neoplasm Metastasis
Mortality
Cause of Death
Random Allocation
Cohort Studies
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation : Radiation Therapy Oncology Group trial 92-02. / Pollack, Alan; Desilvio, M.; Khor, L. Y.; Li, R.; Al-Saleem, T. I.; Hammond, M. E.; Venkatesan, V.; Lawton, C. A.; Roach, M.; Shipley, W. U.; Hanks, G. E.; Sandler, H. M.

In: Journal of Clinical Oncology, Vol. 22, No. 11, 01.12.2004, p. 2133-2140.

Research output: Contribution to journalArticle

Pollack, Alan ; Desilvio, M. ; Khor, L. Y. ; Li, R. ; Al-Saleem, T. I. ; Hammond, M. E. ; Venkatesan, V. ; Lawton, C. A. ; Roach, M. ; Shipley, W. U. ; Hanks, G. E. ; Sandler, H. M. / Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation : Radiation Therapy Oncology Group trial 92-02. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 11. pp. 2133-2140.
@article{a967bcd0f4e24a15b164a6ac5acd5410,
title = "Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group trial 92-02",
abstract = "Purpose: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT)-treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods: There were 537 patients (35.5{\%}) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5{\%} and 7.1{\%} were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results: Median Ki67-SI was 6.5{\%} (range, 0{\%} to 58.2{\%}). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001 ), CSD (P < .0001 ), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5{\%} Ki67-SI cut point was not significant. The 7.1{\%} cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.",
author = "Alan Pollack and M. Desilvio and Khor, {L. Y.} and R. Li and Al-Saleem, {T. I.} and Hammond, {M. E.} and V. Venkatesan and Lawton, {C. A.} and M. Roach and Shipley, {W. U.} and Hanks, {G. E.} and Sandler, {H. M.}",
year = "2004",
month = "12",
day = "1",
doi = "10.1200/JCO.2004.09.150",
language = "English",
volume = "22",
pages = "2133--2140",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "11",

}

TY - JOUR

T1 - Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation

T2 - Radiation Therapy Oncology Group trial 92-02

AU - Pollack, Alan

AU - Desilvio, M.

AU - Khor, L. Y.

AU - Li, R.

AU - Al-Saleem, T. I.

AU - Hammond, M. E.

AU - Venkatesan, V.

AU - Lawton, C. A.

AU - Roach, M.

AU - Shipley, W. U.

AU - Hanks, G. E.

AU - Sandler, H. M.

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Purpose: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT)-treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001 ), CSD (P < .0001 ), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

AB - Purpose: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT)-treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DM (P < .0001 ), CSD (P < .0001 ), and OD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Conclusion: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

UR - http://www.scopus.com/inward/record.url?scp=2942644682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942644682&partnerID=8YFLogxK

U2 - 10.1200/JCO.2004.09.150

DO - 10.1200/JCO.2004.09.150

M3 - Article

C2 - 15169799

AN - SCOPUS:2942644682

VL - 22

SP - 2133

EP - 2140

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 11

ER -