The results of this study demonstrate that NNS with antioxidant activity do not interfere with the effectiveness of radiation therapy as a definitive treatment for limited-stage prostate cancer. Using PSA level as a surrogate for clinical tumor response and control, there were no differences between +NNS and −NNS patients with respect to the magnitude, kinetics, or durability of the PSA response. This was true for patients who did not receive hormonal therapy wherein the PSA response is an excellent surrogate for the direct tumor killing effects of the radiation therapy. It was also true in patients who received hormone ablation therapy wherein the PSA response in the early post-treatment interval is a reflection of the effects of androgen deprivation, but the long-term follow-up PSA level is an excellent surrogate for continued tumor control. Finally, the results also demonstrate that NNS with antioxidant activity do not negatively impact the incidence of biochemical failures in patients with limited-stage prostate cancer for at least 24 months post-treatment.
An exploratory analysis of treatment related-morbidities using the AUA self-assessment showed equivalent effects of radiation treatment in the NNS-treated and nontreated groups with respect to urinary performance. With respect to sexual potency, both groups showed a decline in the relative numbers of patients with adequate function at 12 and 24 months following the end of treatment, with the incidence of patients with adequate sexual function declining significantly in the −NNS cohort but not in the +NNS cohort. Taken together, the results demonstrate that NNS, integrated into radiation therapy treatment programs for early-stage prostate cancer, are clinically safe and appropriate.
This study differs from other studies in the literature in several important ways. First, the study elucidates the impact of NNS treatment with antioxidant activity on the direct tumor response to radiation therapy rather than overall effects on survival. While overall and disease-free survival are the most important benchmarks for any cancer therapy program, the tumor treatment response is a more immediate and quantifiable measure that would be expected to indicate untoward effects, if any, of antioxidant supplements on the effectiveness of radiation therapy. This study, given its retrospective uncontrolled design, provides preliminary evidence that NNS with antioxidant activity do not interfere with the capacity of radiation therapy to kill prostate cancer in vivo in patients.
The fact that complementary and alternative medicine (CAM) supplements had no effect on either the magnitude or the velocity of the PSA response to radiation treatment, in both hormone-treated and nontreated patients with prostate cancer indicates that antioxidants do not alter the sensitivity of tumor tissues to radiation therapy. This in turn suggests that supplements neither inhibited nor amplified the generation of ROS or the effectiveness of ROS-mediated oxidation reactions on the growth and survival of prostate cancer tissues in vivo. While this result may not validate the use of supplements as an adjunct to radiation therapy in prostate cancer, it does provide support and reassurance for their use in patients who wish to take them.
Another important distinction between the current study and most others is the heterogeneity of the NNS provided to the patients in this investigation. Supplements taken by patients in this study were not consistent across the population with respect to either their chemical nature or their mechanism of action. Thus, their in vivo effects are expected to be complex, with multiple physiologic processes affected. Nevertheless, all patients were treated with at least one supplement with significant antioxidant activity, while the majority received two or more antioxidants continuously during the course of their radiation therapy and 2+ years of follow-up. However, it is possible that different supplements might demonstrate different trends toward tumor response, which might be lost when data showing opposing effects are aggregated. As a result, future studies with larger sample sizes and a detailed description of the number and type of NNS used by patients are needed to unravel such trends.
The use of NNS in patients with cancer has been advocated by proponents as a means of diminishing the toxic effects of treatment. In the current study, it is relevant to note that sexual potency was diminished following treatment in both supplement-treated and nontreated patients. Although the decline reached statistical significance only in the non-supplement-treated population, analysis of the variance in levels of potency at equivalent points post-therapy failed to reveal a significant difference between the populations. The same was found for urinary performance based on the AUA score. Thus, it was not possible to demonstrate a beneficial effect of supplements on urinary or sexual morbidities associated with prostate cancer and its treatment in the current study.
Most studies suggesting differential sensitivity of malignant and normal cells to supplement-mediated oxidative metabolic changes have been conducted with squamous epithelial cells of the skin and of the oral cavity.15–17
Comparable studies have not been performed with malignant glandular epithelium of the prostate as yet. The principal finding of the current study does not address this question directly, although the results would be consistent with differential effects. This issue warrants investigation, given the prevalence of cancers of the glandular epithelium and the likelihood that patients afflicted with these malignant diseases may choose to employ NNS with antioxidant activity. Indeed, several recent studies have found a significant increase in vitamin and mineral supplement use in patients following a diagnosis of cancer, with little to no supervision in most cases.1,18,19
While the current study suggests that this is not likely to hamper their tumor response to radiation therapy, the use of such therapies without the knowledge and consent of the attending physician, and where possible, a naturopathic physician, should be discouraged.