Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups?
OBJECTIVE
To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-naïve men with localized prostate cancer.


METHODS
A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-naïve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used.


RESULTS
Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-naïve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy.


CONCLUSIONS
The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.
Galalae
Razvan M
RM
Clinic for Radiation Therapy, University Hospital Schleswig Holstein, Campus Kiel, Germany. galalae@onco.uni-kiel.de
Martinez
Alvaro
A
Nuernberg
Nils
N
Edmundson
Gregory
G
Gustafson
Gary
G
Gonzalez
Jose
J
Kimming
Bernhard
B
D000206:Actuarial Analysis; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D008297:Male; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016019:Survival Analysis
D017430:Prostate-Specific Antigen