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.

• Authors: A Pollack, M DeSilvio, L-Y Khor, R Li, T I Al-Saleem, M E Hammond, V Venkatesan, C A Lawton, M Roach 3rd, W U Shipley, G E Hanks, H M Sandler
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 11 Pg. 2133-40 (Jun 01 2004) ISSN: 0732-183X [Print] United States
• PMID: 15169799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Ki-67 Antigen

Topics

• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Antineoplastic Agents, Hormonal (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Combined Modality Therapy
• Follow-Up Studies
• Humans
• Ki-67 Antigen (metabolism)
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Proportional Hazards Models
• Prostatic Neoplasms (diagnosis, mortality, radiotherapy)
• Survival Analysis