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Study Shows Reduction in Death for Men With Intermediate-Grade Prostate Cancer

Short-term hormone therapy given in combination with radiation therapy to men with early-stage prostate cancer increased their chances of living longer compared with radiation therapy alone, according to a clinical trial supported by the National Cancer Institute (NCI), part of the National Institutes of Health. Benefits of the combined treatment were limited mainly to patients with intermediate-risk disease and were not seen in men with low-risk prostate cancer, researchers say. The results appeared in the New England Journal of Medicine. The Radiation Therapy Oncology Group conducted the trial.

The study, the largest randomized trial of its kind, enrolled nearly 2,000 men with low- and intermediate-risk prostate cancer and followed their health status for more than nine years at 212 centers in the United States and Canada. All study participants had localized, or nonmetastatic, prostate cancer and serum prostate-specific antigen (PSA) levels of less than 20 ng/mL. PSA levels of less than 20, along with normal blood tests and a normal bone scan, indicate that the cancer is low or intermediate risk. Patients were randomly assigned to treatment with radiation alone or radiation plus short-term androgen deprivation therapy (ADT) using drugs that drastically lowered their natural production of testosterone, a hormone that feeds prostate cancer growth.

In addition to investigating whether the participants lived longer on one therapy compared with another, the researchers also looked at whether deaths occurred due to prostate cancer or some other cause, whether the prostate cancer spread, and several other outcomes. Study results were further analyzed on the basis of whether patients had low-risk or intermediate-risk disease. Risk was assessed using several parameters, including Gleason score (the grade of the tumor assigned by a pathologist based on an analysis of tissue samples from a biopsy), PSA level, and clinical stage of disease. Intermediate-risk men had higher Gleason, PSA, and clinical stage values than low-risk men.

The researchers reported a statistically significant improvement in the overall survival after 10 years on the trial for participants who received the short-term ADT and radiation compared with those who received radiation therapy alone (62% vs. 57% overall survival). Radiation therapy plus short-term ADT was also associated with fewer prostate cancer-related deaths compared with radiation therapy alone (8% vs. 4% for the entire study population).

“This study has important significance for clinical care,” says the lead author Christopher U. Jones, MD, with Radiological Associates of Sacramento, Calif. “We now have strong scientific evidence about which patients with early-stage prostate cancer benefit from short-term ADT. This is important both for improved clinical care and the utilization of healthcare resources.”

Prostate cancer rates are higher among black men than other racial/ethnic groups. Therefore, this trial recruited nearly 400 black men, allowing evaluation by racial subgroups. Similar benefits from short-term ADT were seen in white and black populations for 10-year overall survival, disease-specific mortality, and climbing PSA levels after initially lowered levels due to ADT. The strong minority representation in this study will permit additional in-depth analyses of the effects of these therapies in different populations in the future.

Among men with low-risk disease, short-term ADT produced little improvement in 10-year overall or disease-specific survival. It is possible that for patients with low-risk disease, longer follow-up is required to reveal a benefit. However, given that short-term ADT has substantial quality-of-life consequences, including hot flashes and higher rates of erectile dysfunction, and the 10-year disease-specific mortality in the radiation-alone arm for men with low-risk disease was 1%, the researchers noted that these findings do not support adding short-term ADT for low-risk prostate cancer. Newer high-dose radiation treatments may also lessen the need for use of ADT in low-risk patients.

“This type of trial is the gold standard for proving one therapy, or combination of therapies, is more effective than another, and NCI is strongly committed to sponsoring and conducting even more of these types of trials in the future,” says Jeff Abrams, MD, associate director of NCI’s Cancer Therapy Evaluation Program. “Enrolling enough patients in clinical trials is always a challenge, and we owe a great deal of gratitude to the men who participated in this trial because these results will bring benefits to many men facing prostate cancer.”

— Source: National Institutes of Health