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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Pollack
A
A
Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111-2497, USA. A_Pollack@fccc.edu
DeSilvio
M
M
Khor
L-Y
LY
Li
R
R
Al-Saleem
T I
TI
Hammond
M E
ME
Venkatesan
V
V
Lawton
C A
CA
Roach
M
M
Shipley
W U
WU
Hanks
G E
GE
Sandler
H M
HM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000532:radiotherapy; D016019:Survival Analysis
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen