British Journal of Urology (1998), 81, 730–734 Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial L.C. CLARK 1 , B. DALKIN 2 , A. KRONGRAD 2 , G.F. COMBS Jr 3 , B.W. TURNBULL 4 , E.H. SLATE 4 , R. WITHERINGTON 5 , J.H. HERLONG 6 , E. JANOSKO 7 , D. CARPENTER 8 , C. BOROSSO 9 , S. FALK 10 and J. ROUNDER 1 1Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, 2Departments of Urology and Medicine, University of Miami School of Medicine and Geriatric Research, Education, and Clinical Center, VA Medical Center, Miami, FL, 3Division of Nutritional Sciences, Cornell University, Ithaca, NY, 4Statistics Center, Cornell University, Ithaca, NY, 5Medical College of Georgia, Augusta, GA, 6College of Medicine, University of South Carolina, Columbia, SC, 7School of Medicine, East Carolina University, Greenville, NC, 8Macon GA, 9Warner Robbins GA, 10Veterans Administration Hospital, University of Connecticut, Newington, CT, USA Objective To test if supplemental dietary selenium is treatment lag, (RR=0.26 P=0.009). There were sig- nificant health benefits also for the other secondary associated with changes in the incidence of prostate cancer. endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no Patients and method A total of 974 men with a history of either a basal cell or squamous cell carcinoma were significant change in incidence for the primary endpo- ints of basal and squamous cell carcinoma of the skin. randomized to either a daily supplement of 200 mg of selenium or a placebo. Patients were treated for a In light of these results, the ‘blinded’ phase of this trial was stopped early. mean of 4.5 years and followed for a mean of 6.5 years. Results Selenium treatment was associated with a sig- Conclusions Although selenium shows no protective eCects against the primary endpoint of squamous and nificant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983–93. There basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, prostate cancer, and total cancer incidence and mor- tality that demand further evaluation in well- RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate- controlled prevention trials. Keywords Prostate cancer, selenium, chemoprevention, specific antigen (∏4 ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases cancer screening, diet, trace minerals, nutrition, epi- demiology, clinical trials were diagnosed in the placebo group after a 2 year products [6], protease inhibitors [7], retinol [8], vitamin E Introduction [9] and the essential trace element selenium (Se) [10,11]. The introduction of PSA screening for prostate cancer Prostate cancer is the most common cancer and the second leading cause of cancer death in American men coincided with a dramatic increase in incidence in the late 1980s and early 1990s, presumably because of the [1]. It is estimated that in 1997, there will be 209 000 new prostate cancer cases and 41 800 deaths from earlier diagnosis of prevalent cases of cancer. The inci- dence doubled from 1984 to 163/100 000 in 1993 in prostate cancer. The epidemiology of prostate cancer is complex, with few established risk factors; those most the USA. This dramatic increase in incidence in the past decade underscores the importance of enhancing pri- established are family history, age, country, race and testosterone deficiency [2]. Interest in the role of diet in mary and secondary prevention eCorts, although the benefits of PSA screening are still controversial. the aetiology of prostate cancer is increasing with several proposed associations [3]. Dietary factors which have The largest current phase III prostate cancer preven- tion trial [12] uses a prevention strategy based on been investigated include dietary fat [4,5], lycopene, soy antiandrogen therapy with a 5a-reductase inhibitor which prevents the formation of 5a-dihydrotestosterone, Accepted for publication 12 January 1998 730 © 1998 British Journal of Urology