SELECT at 25: Still Driving Discovery

Twenty-five years ago this month, SWOG activated what would be the largest prostate cancer prevention trial ever conducted – the SELECT Selenium and Vitamin E Cancer Prevention Trial (S0000).

Following earlier research that had suggested the antioxidants vitamin E and selenium could reduce men’s risk of prostate cancer, the National Cancer Institute sponsored a definitive prevention study. SWOG designed and led that study – a four-arm, randomized, placebo-controlled trial that tested the supplements alone and in combination.

SELECT opened in late July of 2001, enrollment was brisk, and by June 2004 – two years ahead of schedule – it closed to accrual, having enrolled 35,533 men at 427 centers across the U.S. and Canada.

Although it was expected that these men would take supplements for up to 12 years, a planned futility analysis just seven years in concluded none of the arms would see the 25 percent reduction in prostate cancer incidence the trial was designed to detect.

In fall of 2008, the intervention was stopped, and the publication of primary results in JAMA reported that none of the arms had seen a reduction in prostate cancer incidence. In fact, the data hinted at a possible increase in prostate cancer risk for those on the vitamin E arm. 

To continue collecting data on long-term effects of SELECT’s interventions, the trial moved to centralized follow-up, and roughly one half of the original participants agreed to be monitored by mail and online, work which continued until spring of 2014.

In 2011, again in a publication in JAMA, the SELECT researchers reported that, with a median follow-up time of seven years, men on the vitamin E arm had a 17 percent higher risk of developing prostate cancer than those on the placebo arm.

Although the trial’s unexpected findings helped change the way we think about the cancer prevention potential of supplements, it may have since had an even greater impact in the large number of follow-on studies that have generated new insights from SELECT’s biorepository of blood, tissue, and toenail samples, coupled with its library of data amassed over 13 years of intervention and follow-up.

Among the many secondary analyses of those data that have been published, several recent ones have linked SELECT records to external data sources in innovative ways to ask and answer questions well beyond the trial’s original objectives. 

One 2024 analysis linked trial records to Medicare claims data to characterize the long-term treatment-related side effects and complications faced by men who had undergone prostate cancer therapy years earlier.

Another queried the National Death Index to learn whether the four-plus years of antioxidant supplements taken by most SELECT participants had altered their lifespans (the answer – overall survival was nearly identical across SELECT’s four arms).

If you’re interested in using the SELECT biorepository’s resources or data in your own research, here’s what’s available and how to submit a proposal. These resources may offer particularly attractive opportunities for early-career investigators.

The SELECT bibliography now exceeds 200 publications, almost all of which you can find listed on the SWOG website – go to the S0000 trial page and scroll down to expand the “Publications” section of the page (note that you can follow these steps to generate a bibliography for any SWOG study).

Among the most influential trials SWOG has conducted, SELECT continues to offer opportunities for important research. And many of those who led or worked on the trial are still pushing the envelope within SWOG or are still caring for patients – and enrolling them to SWOG trials – at our member sites.

SELECT’s history is still being written, and its contributions are still being published. So, while technically a negative trial, it’s also a huge, continuing success!