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Radiation plus hormone therapy benefited older men with prostate cancer

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January 21, 2015

The addition of radiation therapy to androgen deprivation therapy improved survival among elderly men with locally advanced prostate cancer, according to an observational study.

The combination of radiation therapy and ADT reduced cancer-related deaths by nearly 50% in men aged 76 to 85 years compared with ADT alone, results showed.

Justin E. Bekelman, MD

Justin E. Bekelman

That finding is particularly striking given that about 40% of men aged older than 75 years diagnosed with locally advanced or high-risk screen-detected prostate cancers only undergo ADT, according to researchers.

“Too many elderly men with potentially curable locally advanced prostate cancer receive hormone therapy alone,” Justin E. Bekelman, MD, assistant professor of radiation oncology at Abramson Cancer Center at the University of Pennsylvania, told HemOnc Today. “But hormone therapy is not a curative treatment. So, men and their doctors need to carefully consider the proven survival benefits of options like radiation and hormone therapy as they make treatment decisions. Age alone should not preclude a man with aggressive prostate cancer from receiving effective care treatment.”

Bekelman and colleagues used data from the SEER–Medicare database to conduct nonrandomized effectiveness studies in three groups of patients diagnosed between 1995 and 2007 and observed through 2009.

The first group was a randomized clinical trial cohort that consisted of men aged 65 to 75 years. The second group, considered the “elderly” group, consisted of men older than 75 years. The final cohort included men aged at least 65 years with screen-detected high-risk prostate cancer.

In total, the analyses consisted of 31,541 men.

In the randomized clinical trial group, the combination of ADT and radiation therapy was associated with reduced cause-specific mortality (HR=0.39; 95% CI, 0.34-0.45) and all-cause mortality (HR=0.57; 95% CI, 0.54-0.61) compared with ADT alone.

In the elderly cohort, the combination of ADT and radiation therapy was associated with reduced cause-specific mortality (HR=0.51; 95% CI, 0.44-0.59) and all-cause mortality (HR=0.63; 95% CI, 0.59-0.67) compared with ADT alone.

In the screen-detected cohort, the combination of ADT and radiation therapy also was associated with reduced cause-specific mortality (HR=0.25; 95% CI, 0.19-0.33) and all-cause mortality (HR=0.5; 95% CI, 0.45-0.55).

“This study is important because it brings needed attention to the effectiveness of cancer treatments for the elderly,” Bekelman said. “Men with aggressive prostate cancer regardless of age — whether they are in their 50s, 60s, 70s, or 80s — should know that radiation with hormone therapy saves lives and is tolerable.”

The findings highlight “the prevalent age bias against the use of radiation therapy” among older men with high-risk prostate cancer, Dean A. Shumway, MD, and Daniel A. Hamstra, MD, PhD, both from the department of radiation oncology at the University of Michigan, wrote in an accompanying editorial.

“Much of the public discourse relating to prostate cancer emphasizes the overtreatment of low-risk prostate cancer in men who are least likely to die as a result of prostate cancer,” Shumway and Hamstra wrote. “Given the weight of the evidence favoring the addition of radiation therapy to ADT for high-risk disease, one must question why — in the population [in this study] — 49% of men older than age 65 years … were treated with ADT monotherapy, a rate that increased to 61% in those age 75 years and older.”

It is possible that the prevalence of ADT monotherapy could be explained by financial incentives that “favor discretionary use in scenarios of uncertain clinical benefit,” and that the benefits of definitive local therapy were unknown at the time many of the patients in this study were treated, Shumway and Hamstra wrote.

“However, it is also critical to note that the use of primary ADT has been found to be highly related to which practitioners a patient sees rather than to patient or tumor characteristics,” they wrote. “In elderly men who are sufficiently healthy to tolerate ADT, careful consideration should be given to also treating with radiation therapy, which is associated with substantial improvements in disease-specific [survival] and OS and can be delivered with minimal morbidity using modern treatment techniques.” – by Anthony SanFilippo

For more information:

Justin E. Bekelman, MD, can be reached at the Hospital of the University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104; email: mailto:justin.bekelman@uphs.upenn.edu.

Disclosure: The researchers report speakers’ bureau payment and research funding from Pfizer, as well as speakers’ bureau payment from Janssen.

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PERSPECTIVE
Padraig Warde

Padraig Warde

Approximately 220,000 men will be diagnosed with prostate cancer in the United States in 2015. Of these, 10% to 20% will present with locally advanced disease, or extension of the tumor beyond the confines of the prostate gland (clinical T3 disease). For many years, there was considerable uncertainty whether the addition of radiation therapy to the prostate in addition to androgen deprivation therapy improved outcome in this group of patients. Two landmark randomized clinical trials (RCTs) published in the past 2 to 3 years have clearly demonstrated that there is a significant improvement in OS and disease-specific survival with combined-modality therapy (ADT plus radiation therapy) compared with ADT alone.
This study by Bekelman and colleagues set out to see if the survival benefit of combined-modality therapy seen in both RCTs holds true in real-world clinical practice. Their analysis of 31,451 patients identified through the SEER–Medicare database showed patients treated with ADT plus radiation therapy had a significant improvement in cause-specific survival and OS. Patients treated with ADT plus radiation therapy were more than 50% less likely to die of prostate cancer than patients treated with ADT alone. Interestingly, the magnitude of benefit seen in this study was similar to that seen in both RCTs. Similar benefits were seen in elderly patients and screen-detected patients, two groups that were under-represented in the RCTs.
ADT alone is a non-curative, common (used in approximately 40% cases) treatment for locally advanced prostate cancer in the United States, particularly in the elderly. This study, along with the two RCTs, suggests that prostate radiation therapy should be considered in all cases to improve OS and cause-specific survival.

Padraig Warde, MB, ChB, BAO, FRCPC
Princess Margaret Cancer Centre

Disclosure: Warde reports no relevant financial disclosures.