The differences among therapies were more prominent at higher levels of cancer risk, and suggest, the researchers say, that in many cases surgery should play a greater role in treatment strategies for patients with prostate cancer that is likely to recur or spread.
The study is available online in the journal “Cancer,” the journal of the American Cancer Society, at http://www3.interscience.wiley.com/journal/123630095/abstract
Most previous reports comparing treatment outcomes among different treatment options have looked only at PSA responses to treatment, rather than at the more important long-term survival outcomes, according to the researchers. Measuring levels of PSA, or prostate-specific antigen, in the blood, is intended to help determine whether prostate cancer has recurred or spread, although in many cases a rising PSA level does not necessarily mean the cancer will progress.
Roughly one man in six will be diagnosed with prostate cancer, which is the second leading cause of cancer death in American men, according to the American Cancer Society.
“Despite the high incidence of prostate cancer, there is relatively little high-quality evidence on which to base current treatments for localized disease,” said Matthew R. Cooperberg, MD, MPH, lead investigator of the study and a prostate cancer specialist in the UCSF Department of Urology and the UCSF Helen Diller Family Comprehensive Cancer Center.
“These therapies can all have significant side effects, so it’s important to understand which treatment alternatives are most effective. In current practice, likelihood of undergoing surgery falls progressively with increasing levels of risk, which may be exactly contrary to what the treatment pattern should be,” he said.
Researchers found that the risk for cancer-specific mortality was more than three times higher in patients who received hormone therapy versus radical prostatectomy (surgical removal of the prostate) and more than twice as high in patients who received external-beam radiation therapy versus prostatectomy.
For men at low levels of risk, prostate cancer mortality was very uncommon, and differences among the treatment options were small. The survival differences increased substantially for men at intermediate and high risk, according to the analysis, with the greatest relative benefit for surgery seen for men at higher levels of risk.
The American Urological Association’s clinical practice guidelines for localized prostate cancer treatments include active surveillance, radical prostatectomy, external-beam radiation therapy, and brachytherapy (radiotherapy delivered via radioactive seeds), but draw no conclusions about the relative efficacy of each.
Androgen-deprivation therapy, which suppresses the production of male sex hormones, is not endorsed by the American Urological Association clinical practice guidelines for localized prostate cancer, due to inadequate evidence regarding outcomes, yet it is commonly used in practice, the researchers state.
“This is a clear signal to the physician community that prostatectomy should be considered for men with higher-risk prostate cancer. In many cases, surgery would be part of a multimodal treatment approach, including adjuvant radiation or systemic treatments based on the pathology and early PSA response,” added Peter R. Carroll, MD, MPH, chair of the UCSF Department of Urology and leader of the Prostate Program at the UCSF Helen Diller Family Comprehensive Cancer Center. Carroll is senior author on the paper.
Because no adequate randomized trials have compared active treatments for localized prostate cancer, the authors analyzed risk-adjusted, cancer-specific mortality outcomes among men who underwent radical prostatectomy, external-beam radiation therapy, or primary androgen deprivation.
The research team analyzed data from 7,538 men with localized disease from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry, a national disease registry comprising men from 40 urologic practice sites from across the country. The team then compared outcomes across treatments after adjusting for risk and age. In total, 266 men died of prostate cancer during follow-up.
Co-authors of the paper are Andrew J. Vickers, PhD, of the Memorial Sloan-Kettering Cancer Center; Jeanette M. Broering, RN, MS, MPH, of the UCSF Department of Urology and the UCSF Helen Diller Family Comprehensive Cancer Center; and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) Investigators.
CaPSURE is supported in part by Abbott Laboratories and also is funded internally by the UCSF Departments of Urology. This work also was supported by the National Institutes of Health.
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