DENVER-Dose escalation of high dose rate (HDR)
brachytherapy may improve long-term survival in men with intermediate- or
high-risk prostate cancer, according to findings of a study presented at the
47th Annual Meeting of the American Society for Therapeutic Radiology and
Oncology (abstract 63).
"A strong dose-response relationship has been seen for
prostate cancer patients in several randomized dose-escalation studies," said
lead author Carlos Vargas, MD. However, he added, a number of phase III trials
have not found any gain in disease-specific and overall survival with higher
radiation doses. Dr. Vargas was a radiation oncologist at William Beaumont
Hospital, Royal Oak, Michigan, at the time of the study, and now is at the
University of Florida, Gainesville.
Dr. Vargas and his colleagues analyzed data from a phase
I/II trial conducted between 1991 and 2003 of dose escalation achieved by an
HDR brachytherapy boost. The study included 197 men with prostate cancer who
had an intermediate or high risk for poor outcomes because of at least one
adverse feature: a Gleason score of 7 or higher (67% of men); a pretreatment
prostate-specific antigen (PSA) level of 10 ng/mL or higher (37%); or a T
stage of T2 or higher (80%). None received androgen deprivation therapy, he
All of the patients received pelvic external-beam radiation
therapy (46 Gy) in fractions delivered daily, 5 days per week, over 5 weeks.
In addition, they received HDR brachytherapy boosts during the first and third
weeks. The HDR dose used was progressively escalated during the study,
resulting in two treatment groups: a low-dose group of 67 patients (mean
prostate biologically equivalent dose [BED], 88.2 Gy) and a high-dose group of
130 patients (mean prostate BED, 116.8 Gy). Their corresponding median
durations of follow-up were 7 and 4.5 years, Dr. Vargas said.
In Kaplan-Meier analyses, compared with patients in the
low-dose group, those in the high-dose group had significantly lower 5-year
estimated rates of biochemical failure according to the ASTRO definition (14%
vs 33%); clinical failure, defined as local failure or distant metastases (6%
vs 16%); and cancer events (14% vs 36%). Further, the high-dose group had
significantly better 5-year estimated rates of clinical disease-free survival
(92% vs 76%), cause-specific survival (100% vs 95%), and overall survival (98%
Stepwise Cox multivariate analyses that accounted for a
variety of factors (T stage, Gleason score, pretreatment PSA level, age, and
HDR brachytherapy dose) further showed that a high dose of HDR brachytherapy
vs a low dose was independently associated with reduced risks of biochemical
failure (hazard ratio, 0.46), prostate-cancer-related events (0.41), clinical
disease (0.35), and death (0.14). "Higher doses were associated with larger
than twofold improvements for all outcomes measured," Dr. Vargas observed.
The investigators concluded that intermediate- and
high-risk prostate cancer shows a strong dose-response relationship. "High
radiation doses with a hypofractionated accelerated regime improved
biochemical and clinical control, ultimately leading to better cancer-specific
survival and overall survival," Dr. Vargas commented. "From this trial, it
appears that high radiation doses alone can improve survival in intermediate-
and high-risk patients." He noted that the results will have to be confirmed
in a prospective randomized trial.