In a recent study published in JAMA Network Open, researchers investigated the use of vitamin E and selenium in preventing the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC).

Study: Selenium and Vitamin E for Prevention of Non–Muscle-Invasive Bladder Cancer Recurrence and Progression. Image Credit: Evan Lorne/Shutterstock.com

Background

Bladder cancers are the 12^th most prevalent form of cancer in the world. The most common form of bladder cancer in high-income countries is transitional cell carcinomas originating from urothelial tissue, and these often present as NMIBC. The initial treatment for NMIBC is transurethral resection of the tumor, along with adjuvant intravesical therapy. However, 80% of the patients experience recurrence of the cancer, and 45% of the NMIBC cases progress to invasive muscle bladder cancer.

Considering the chronic nature of NMIBC and the rate of recurrence and progression of the cancer, chemoprevention has been considered as a potential option to reduce the recurrence rates. Furthermore, while clinical trials investigating the use of vitamin E and selenium in the prevention of primary and secondary cancers have not reported beneficial effects, neither have the reported detrimental effects.

Therefore, vitamin E and selenium continue to be investigated as potential chemoprevention agents for various cancers such as NMIBC.

About the study

In the present study, the researchers reported on the placebo-controlled, double-blinded, randomized clinical trial known as the selenium and vitamin E as adjuvant therapies for NMIBC trial (SELENIB trial), which recruited newly diagnosed NMIBC patients above the age of 18 with urothelial NMIBC confirmed through pathological tests. The participants were randomized within one year of the initial transurethral resection of the tumor.

The participants were randomly assigned to one of four groups being treated with combinations of vitamin E, selenium, or placebos: selenium and placebo, vitamin E and placebo, selenium and vitamin E, and placebo and placebo.

A recurrence risk stratification was used to randomize the assignment of participants to the groups. The treatments were in the form of tablets or capsules, and follow-ups conducted every six months for five years assessed the treatment adherence, disease status, and adverse or toxic effects.

The primary outcome being measured was the recurrence-free interval, while the secondary outcomes consisted of overall survival and progression-free interval. The overall quality of life was also assessed at each of the follow-ups.

The recurrence-free intervals and progression-free intervals of the treatment groups were compared using Kaplan-Meier estimations, while hazard ratios were used to compare the adjusted and unadjusted treatments.

Results

The results reported that not only did selenium supplementation have no impact on cancer recurrence in NMIBC patients, but supplementation with vitamin E increased the risk of recurrence. Vitamin E and selenium supplementation also had no impact on the overall survival or progression of the cancer.

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The recurrence-free interval was not found to be different for the group that compared selenium treatment with placebo, while for the group comparing vitamin E supplementation with placebo, there was a significant decrease in the recurrence-free interval associated with vitamin E supplementation. Furthermore, even after adjusting for known prognostic factors, the Cox proportional hazard ratios indicated no change in findings.

While the adverse events reported were not different across treatment groups and were not considered related to the trial treatment, 85 of the 1957 adverse events reported were serious. Fatigue, cough or cold, and dermatitis were the most common adverse events reported.

In the selenium treatment group, there were 60 recurrences in the selenium arm, while the placebo arm had 62 recurrences. However, the recurrences for vitamin E and the placebo arms in the vitamin E treatment group were 72 and 50, respectively, and vitamin E was associated with a significant decrease in the recurrence-free interval.

Other studies have shown that dietary supplementation with vitamin E significantly increases prostate cancer risk in healthy men, and the present results added to those findings by highlighting the role of vitamin E supplementation in increasing the recurrence risk of NMIBC. Given the easy availability of over-the-counter vitamin E supplements, these results emphasize the need for caution in using such dietary supplements.

Conclusions

Overall, the findings reported that while selenium supplementation had no beneficial or detrimental effects on the recurrence of NMIBC, vitamin E supplements significantly increased the risk of recurrence in NMIBC patients.

The results highlighted the importance of caution while using dietary supplements and the need for further studies on the underlying biological mechanisms of the impact of vitamin E on cancer recurrence.

Journal reference:

• Bryan, R. T., Pirrie, S. J., Abbotts, B., Maycock, S., During, V., Lewis, C., Grant, M., Bird, D., Devall, A. J., Michael, W., D, James, N. D., Billingham, L. J., Zeegers, M. P., K, C. K., & SELENIB Investigators. (2023). Selenium and Vitamin E for Prevention of Non–MuscleInvasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial. JAMA Network Open, 6(10), e2337494–e2337494. doi: https://doi.org/10.1001/jamanetworkopen.2023.37494