The role of overall treatment time in the outcome of radiotherapy of prostate cancer: an analysis of biochemical failure in 4839 men treated between 1987 and 1995.
OBJECTIVE
Assess the importance of overall time (OT) and dose for biochemical failure (BF) after external-beam radiotherapy of prostate cancer in a retrospective analysis of a nine-institution database with 4839 patients.


METHODS
Relevant baseline factors (T stage, Gleason score, initial PSA) were available for 4338 men. Cox models were used to estimate the effects of dose and OT corrected for baseline factors, treatment year, institution and interactions, and differences in post-treatment PSA-measurement intervals. After exclusion of very short and long intervals, patient numbers were 1445 events/3426 at risk (endpoint all BFs), and 1177 events/3354 at risk (endpoint exclusion of BFs that were likely distant failures). Separate analyses were carried out by risk group for men who received <70 Gy and > or = 70 Gy.


RESULTS
Neither dose nor OT was significant when the analysis was restricted to doses <70 Gy, while for patients treated to 70 Gy or higher there were significant influences of both dose and OT on outcome in low- and intermediate-risk patients. These effects were quantified as a relative increase after 5 years followup of 6% in BFs for a 1-week increase in OT, a relative decrease of 15% in BFs for a 6-Gy increase in dose, and a dose equivalent of proliferation of 0.24 Gy/day. As the dose per fraction was nearly constant, the data contain no information on the alpha/beta ratio.


CONCLUSIONS
The results show that OT and dose are significant determinants of outcome of radiotherapy in low- and intermediate-risk patients treated to 70 Gy or higher, and suggest that meaningful improvements in outcome may be targeted by modest increases in total dose and decreases in OT.
Thames
Howard D
HD
Division of Quantitative Sciences, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. hdt@wotan.mdacc.tmc.edu
Kuban
Deborah
D
Levy
Larry B
LB
Horwitz
Eric M
EM
Kupelian
Patrick
P
Martinez
Alvaro
A
Michalski
Jeffrey
J
Pisansky
Thomas
T
Sandler
Howard
H
Shipley
William
W
Zelefsky
Michael
M
Zietman
Anthony
A
D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D017430:Prostate-Specific Antigen