Reviewed by: Neha Vapiwala, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 10, 2004
Authors: D'Amico, A. et al.
Affiliations: Dept. of Rad Onc, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA
Source: JAMA , August 18, 2004, Vol 292, No. 7
In addition to overall survival, disease-specific survival is a very useful endpoint in cancer epidemiology. The latter can be particularly instructive in older patient groups that generally have a high incidence of comorbidities and intercurrent deaths. While overall survival can reflect the impact of all competing causes of mortality, disease-specific survival can better reflect the efficacy of a given intervention in preventing a cancer-related death. In prostate cancer , it is well recognized that the proportion of deaths attributable to this diagnosis rises with the stage, PSA level, and Gleason score. As a result, these intermediate and high-risk subsets of patients continue to be the subjects of ongoing research for better treatment outcomes, including the study discussed here.
The current standard of care in the treatment of high-grade clinically localized prostate cancer is external beam radiation therapy (EBRT) to a dose of about 70 Gray (Gy). Pollack et al . have used higher radiation doses to achieve improved biochemical-disease-free survival rates, with PSA progression serving as a surrogate for disease progression. However, a relatively higher PSA level post-treatment does not reliably predict for death from prostate cancer in most cases, ie: it is not a consistent or linear relationship. To date, the survival data from the study of dose escalation in prostate cancer are not published, and so the standard dose remains 70 Gy. In contrast, an overall survival benefit has been shown with the addition of androgen suppression therapy (AST) for 3 years duration to 70 Gy EBRT (Bolla et al ).
However, the well-described adverse effects of long-term AST prompted this study by D'Amico et al . The goal was to evaluate whether the use of AST for six months duration with EBRT provides a survival benefit over EBRT alone. In other words, does decreasing the duration of AST from 36 months to 6 months eliminate the previously documented survival benefit?
Prospective, unblinded, randomized study of 206 patients enrolled between 1/1/95 and 4/15/01 from Harvard Outreach hospitals and medical centers
The results of this study suggest that the addition of 6 months of AST to 70 Gy 3-D conformal radiation therapy provides an overall survival benefit in patients with clinically localized prostate cancer. The benefit appears to be of the same magnitude as that provided by 3 years of AST as used in the Bolla trial. The authors point out several important issues that still remain, including whether a larger dose than 70 Gy, or alternatively larger-sized pelvic treatment fields, might have resulted in an even bigger survival benefit. Also, is total androgen suppression always necessary, or would partial blockade suffice still provide the survival advantage?
It is important to note in evaluating this study that there is no AST-only control arm. Finally, and perhaps most importantly, this study can not make any definitive conclusions about 6 months vs. 36 months of AST without actually testing them directly in a randomized study. However, the promising results of this trial certainly have significant clinical implications and suggest the need for further study in this area.