BERKELEY, CA (UroToday.com) - In our recent article, we present the results of a chemoprevention clinical aimed at investigating the effect of selenium on preventing prostate cancer. Prostate cancer is the most common non-skin cancer and the second-most common cause of cancer-related deaths among US men. The American Cancer Society estimates there will be 241 740 new cases and 28 170 deaths due to prostate cancer in 2012. Hence it is important that efforts be made to not only prevent this disease but also to prevent its progression and its associated morbidity and mortality.
| "Concluding that selenium is ineffective will allow us to divert our efforts and resources away from selenium in directions more likely to yield promising results towards preventing this disease and its associated morbidity and mortality." |
Research studies were carried out at our institution during the 1990s to investigate the association between selenium and skin cancer. Although selenium did not indicate an effect on skin cancer, secondary analysis of data from these studies indicated towards a negative association between selenium and prostate cancer. As a result, clinical trials were initiated to investigate the effect of selenium supplementation on various stages of prostate cancer. Three such trials were initiated at our institution. The first trial investigated the effect of selenium supplementation in men diagnosed with prostate cancer who underwent prostatectomy, whereas the second trial investigated the effect of selenium supplementation on preventing cancer progression in men diagnosed with prostate cancer. Although we were able to demonstrate that there is dose-dependent increase in selenium levels within the prostate, selenium did not show any benefit in preventing cancer progression. The third trial, known as the Negative Biopsy Trial (NBT), results of which are reported in the above mentioned article, was carried out to determine if selenium supplementation prevents prostate cancer in men at high risk for this disease. Results of this trial did not demonstrate any benefit of selenium supplementation towards preventing prostate cancer and were in agreement with the results of another large clinical trial (SELECT) conducted to investigate the effect of selenium supplementation in average-risk men.
Although the results of the NBT were negative, it provided us with valuable information about the disease, methods used to diagnose it, and also the difficulties faced in conducting a clinical trial in this population. As part of conducting this trial, detailed patient data consisting of demographic data, lifestyle data (dietary habits, smoking and other substance use habits), and biological data (in the form of blood and prostate tissue samples) were collected. Analyses of these data are currently ongoing and will provide us with valuable insight into the disease process and help us identify targets for future research. For example, we are currently investigating various biomarkers to determine if any of them could be used to improve diagnostic methods for prostate cancer. Another avenue we are examining is whether lifestyle factors increase or decrease likelihood of being diagnosed with prostate cancer, and could modification of these lifestyle factors affect cancer detection.
The field of prostate cancer is constantly evolving. During the time period that the NBT was conducted, prostate biopsy technique has changed considerably. Initially, the routine procedure was to collect six cores during a biopsy. This number has gradually increased, and the current number is around 12-13 cores at our institution, although numbers as high as 23 to 31 cores have also been reported during NBT. This considerably changed the false-negative rates from 20-23% to 11%, adversely affecting the ability of this trial to detect differences between the three treatment groups. In an experiment, one would ideally like the conditions to remain the same during the entire duration of the experiment. However, in reality, it may not be possible in a large long-term multicenter clinical trial such as the NBT -- and in a dynamic and constantly evolving field such as prostate cancer -- and hence factors such as this should be taken into account while designing long-term trials. In a population of elderly men (mean age 65 years, maximum age 80) targeted for NBT, the ability of the participants to adhere to the trial protocol and the effect of associated morbidities on patient recruitment and their interactions with study medications should be thoroughly considered before initiating a trial. Results of SELECT have indicated increased risk of diabetes among men taking selenium during the trial. Interactions such as these need to be carefully considered while planning the next generation of clinical trials.
Results from the NBT provide the valuable last piece in understanding the relationship of selenium with prostate cancer. Concluding that selenium is ineffective will allow us to divert our efforts and resources away from selenium in directions more likely to yield promising results towards preventing this disease and its associated morbidity and mortality.
Written by:
Amit Algotar, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Assistant Research Scientist
The University of Arizona Cancer Center
Tucson, Arizona USA
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