Short-term ADT with RT improves survival in intermediate-risk prostate cancer
MedWire News: A short-term course of androgen-deprivation therapy (ADT) in combination with radiotherapy (RT) significantly reduces disease-specific mortality rates among patients with intermediate-risk prostate cancer compared with radiotherapy alone, report US researchers.
The study results show that the use of ADT for 4 months before and during RT also increased overall survival modestly, but significantly, without incurring more toxic effects.
"These findings have tremendous significance for improving both clinical care and the utilization of health care resources," said lead author Christopher Jones, from the Radiological Associates of Sacramento in California.
Jones and co-investigators randomly assigned 1979 men with stage T1b, T2c, T2a, or T2b prostate cancer and a prostate-specific antigen (PSA) level of 20 ng/ml or less to a total dose of 66.6 Gy RT alone (n=992), or the same dose of RT with 4 months of ADT (n=987; flutamide at 250 mg orally three times per day with either subcutaneous goserelin or intramuscular leuprolide), beginning 2 months before RT initiation.
The overall 10.0-year survival rate after a median 9.1-year follow-up was 62% among patients receiving RT plus ADT, and 57% among patients receiving RT alone. The disease-specific mortality during this time period was significantly less among men treated with combined therapy than among those treated only with RT, at 8% versus 4%.
Having a Gleason score of 7 or higher was the only significant independent negative predictor of all outcomes, including; overall survival, disease-specific mortality, distant metastasis, and biochemical failure (a rising PSA after treatment).
Rates of acute and late hepatic and gastrointestinal toxic effects were similar between the two treatment groups, and the incidence of grade 3 or higher ADT-related effects was less than 5%, report the researchers. There was a mild increase in erectile dysfunction among ADT plus RT patients at one year post-treatment, but the between-group difference was not significant, they add.
Jones and team conducted a subanalysis of treatment efficacy according to disease stratification (low, intermediate, or high) and found that the addition of ADT showed the greatest clinical benefit in patients with intermediate-risk cancer, defined as Gleason score 7, or Gleason score 6 or less with a PSA level of 10-20 ng/ml, or stage T2b.
For these intermediate-stage patients, the overall survival rate with addition of ADT was 61%, compared with 54% for RT treatment alone, and disease-specific mortality reduced from 10% to 3% during this period. No significant survival benefit was seen for additional ADT among low-risk patients, nor among high-risk men, however, there was only a small number in the latter group available for analysis, the researchers report in NEJM.
Commenting on the research, Anthony D'Amico (Brigham and Women's Hospital, Boston, Massachusetts) questions whether longer durations of hormonal therapy would reduce mortality rates further.
"Whether 4 or 6 months of hormonal therapy for intermediate-risk disease is best requires further study," he suggested.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Sarah Guy