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Worsening Anemia Signals Poorer Outcomes In Men Treated For Advanced Prostate Cancer

OHSU Cancer Institute researcher presented first study demonstrating relationship between hemoglobin change during treatment and survival for men with advanced prostate cancer

Researchers from the Oregon Health & Science University Cancer Institute and Southwest Oncology Group have identified a new method of determining how men with advanced prostate cancer will respond to treatment. They found that worsening anemia during the first three months of hormonal therapy for prostate cancer that has spread predicts shorter survival and earlier relapse.

"These results suggest that by monitoring anemia during the first three months of treatment, we can provide men with a better idea of how well they will fare," said principal investigator Tomasz Beer, M.D., director of the prostate cancer research program in the OHSU Cancer Institute. Beer presented results of this study at the 101st Annual Meeting of the American Urological Association in Atlanta on Tues., May 23.

Researchers also found that race alone was not a strong predictor of survival or disease progression. However, they found that men with the same hemoglobin levels before treatment experienced significantly different overall and progression-free survival depending on whether they were black or white. Hemoglobin levels in the blood are measured to monitor anemia. Lower levels of hemoglobin are considered anemic.

"Outcomes for prostate cancer have always been worse for black men than their white counterparts and the reasons behind this have not been fully understood," Beer said. "Differences in anemia could help us understand why blacks do worse and maybe make it possible to do something about it."

Overall, researchers found that anemic blacks fare worse than anemic whites and that blacks with high baseline hemoglobin fare better than whites with similar hemoglobin levels.

"Our study was not designed to answer questions about this complex and novel finding, but we are examining a number of hypotheses," Beer said.

Anemia is common among newly diagnosed prostate cancer  patients with metastatic disease. Approximately one-fourth of these men are anemic. Previous studies have shown that men who are anemic prior to treatment experience shorter survival and are prone to early relapse. One recent study has shown that a decrease in hemoglobin after one month of treatment predicts early relapse in men with high-risk prostate cancer that has not spread.

 "Relatively little was known about hemoglobin change after the beginning of hormonal therapy for advanced prostate cancer," Beer said. "We were interested in learning how changes in anemia during early treatment impact survival for these men because there are ways of treating anemia. There may be opportunities to study whether treating anemia would improve survival, making it a modifiable risk factor."

Androgen deprivation, or hormonal therapy, is the standard treatment for prostate cancer that has spread beyond the gland. It blocks the production of male hormones that can promote prostate cancer growth. This common treatment for advanced prostate cancer wipes out most male hormones found in the body. It also is known to reduce red cell production, making anemia one of its adverse effects.

 "We believed that different men would respond to hormonal therapy differently and that these different responses in hemoglobin could be an independent prognostic factor for men with advanced prostate cancer," Beer said. "We also believed that the effect of anemia on outcomes may vary by race."

Beer and his colleagues tested this hypothesis in a retrospective analysis of SWOG 8894, a randomized study of orchiectomy versus orchiectomy plus flutamide in previously untreated metastatic prostate cancer.

Of the 1,286 subjects enrolled in SWOG 8894, data from 817 subjects were available for this analysis, which included a number of other traditional risk factors beyond hemoglobin, including performance status, Gleason score and disease extent.

The median pretreatment hemoglobin was 13.7 g/dL before treatment and 12.8 g/dL after treatment. Overall, the mean change in hemoglobin between the baseline measurement and three-month follow-up was a decrease of 0.54 g/dL. Subjects whose hemoglobin dropped by 1.6 g/dL or more had a 31 percent higher risk of death than those whose hemoglobin increased by more than .3 g/dL.

 "We now know that baseline hemoglobin and three-month hemoglobin change are prognostic, even after taking into account these other risk factors," Beer said. "Further study is needed to fully understand the underlying biology of this affect and to determine if reversing anemia can improve survival in patients with advanced prostate cancer."
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Particulars: AUA Annual Meeting Abstract No. 1197, "Prognostic Value of Hemoglobin Change After Initiation of Androgen Deprivation Therapy for Newly Diagnosed Metastatic Prostate Cancer: A Multivariate Analysis of SWOG 8894."

This study was funded by the National Cancer Institute.

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