Dose Escalation of HDR Brachytherapy May Up Survival

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 noted.

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.

Study Results

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% vs 86%).

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.