Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer

Alexander S. Parker, Michael G. Heckman, Kevin J. Wu, Julia E. Crook, Tracy W. Hilton, Thomas M. Pisansky, Johnny R. Bernard, Steven E. Schild, Li Yan Khor, Elizabeth H. Hammond, Alan Pollack, Steven J. Buskirk

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

Original languageEnglish
Pages (from-to)1364-1370
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume75
Issue number5
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Fingerprint

Salvage Therapy
biomarkers
staining
radiation therapy
Prostatic Neoplasms
Radiotherapy
Biomarkers
cancer
Staining and Labeling
Recurrence
scoring
evaluation
tumors
adjusting
Neoplasms
Tumor Biomarkers
antibodies
Proportional Hazards Models
hazards
confidence

Keywords

  • Ki-67 antigen
  • Prognosis
  • Prostatic neoplasms
  • Salvage radiation therapy
  • Tumor markers

ASJC Scopus subject areas

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

Cite this

Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer. / Parker, Alexander S.; Heckman, Michael G.; Wu, Kevin J.; Crook, Julia E.; Hilton, Tracy W.; Pisansky, Thomas M.; Bernard, Johnny R.; Schild, Steven E.; Khor, Li Yan; Hammond, Elizabeth H.; Pollack, Alan; Buskirk, Steven J.

In: International Journal of Radiation Oncology Biology Physics, Vol. 75, No. 5, 01.12.2009, p. 1364-1370.

Research output: Contribution to journalArticle

Parker, AS, Heckman, MG, Wu, KJ, Crook, JE, Hilton, TW, Pisansky, TM, Bernard, JR, Schild, SE, Khor, LY, Hammond, EH, Pollack, A & Buskirk, SJ 2009, 'Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer', International Journal of Radiation Oncology Biology Physics, vol. 75, no. 5, pp. 1364-1370. https://doi.org/10.1016/j.ijrobp.2008.12.061
Parker, Alexander S. ; Heckman, Michael G. ; Wu, Kevin J. ; Crook, Julia E. ; Hilton, Tracy W. ; Pisansky, Thomas M. ; Bernard, Johnny R. ; Schild, Steven E. ; Khor, Li Yan ; Hammond, Elizabeth H. ; Pollack, Alan ; Buskirk, Steven J. / Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer. In: International Journal of Radiation Oncology Biology Physics. 2009 ; Vol. 75, No. 5. pp. 1364-1370.
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abstract = "Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95{\%} confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.",
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AU - Parker, Alexander S.

AU - Heckman, Michael G.

AU - Wu, Kevin J.

AU - Crook, Julia E.

AU - Hilton, Tracy W.

AU - Pisansky, Thomas M.

AU - Bernard, Johnny R.

AU - Schild, Steven E.

AU - Khor, Li Yan

AU - Hammond, Elizabeth H.

AU - Pollack, Alan

AU - Buskirk, Steven J.

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N2 - Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

AB - Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

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KW - Tumor markers

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