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

Purpose. The Ki-67 staining index (Ki67-Sl) has been associated with prostate cancer patient outcome, however, few studies have involved radiotherapy (RT) -treated patients, The association of Ki67-Sl 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 (STAID) + 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-Sl analysis. Median follow-up was 96.3 months. Ki67-Sl 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-Sl 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), DIM (P < .0001), CSD (P < .0001), and CD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-Sl cut point was not significant. The 7.1 % cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-Sl was the most significant correlate of DIM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAID + RT that did not require LTAD. Conclusion. Ki67-Sl was the most significant determinant of DM and CSD and was also associated with CID. The Ki67-SI should be considered for the stratification of patients in future trials. (C) 2004 by American Society of Clinical Oncology.