Prostate cancer DNA ploidy and response to salvage hormone therapy after radiotherapy with or without short-term total androgen blockade: an analysis of RTOG 8610.
OBJECTIVE
DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (approximately 4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB).


METHODS
The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival.


RESULTS
DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation.


CONCLUSIONS
Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.
Pollack
A
A
Department of Radiation Oncology, Fox Chase Cancer Center, and Radiation Therapy Oncology Group, Philadelphia, PA 19111, USA. A_Pollack@FCCC.edu
Grignon
D J
DJ
Heydon
K H
KH
Hammond
E H
EH
Lawton
C A
CA
Mesic
J B
JB
Fu
K K
KK
Porter
A T
AT
Abrams
R A
RA
Shipley
W U
WU
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D005485:Flutamide / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate
D000726:Androgen Antagonists; D004273:DNA, Neoplasm; D017273:Goserelin; D005485:Flutamide