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. 2023 Jan 20;21(1):e07704. doi: 10.2903/j.efsa.2023.7704

Reference

Study

Country

Design

N randomised/completed

Duration(a)

Recruitment criteria

Subject characteristics at baseline(b) Intervention(b) Outcomes assessed Results

Algotar et al. (2013b)

NBT

USA and New Zealand

RCT

G1, placebo: 232/0 G2, 200 μg Se/d: 234/0 G2, 400 μg Se/d: 233/0

Duration (median): 35 mo

High risk of prostate cancer, as evidenced by PSA > 4 ng/mL and/or suspicious DRE and/or PSA velocity > 0.75 ng/mL per yr; negative prostate biopsy for cancer within 12 mo of enrolment.

Sex: M

Age (yr) G1: 65.5 ± 7.4 G2: 65.2 ± 8.0 G3: 65.5 ± 7.7 BMI (kg/m 2 ): NR Ethnicity (Caucasians, %) G1: 84.2 G2: 83.7 G3: 82.6

Plasma Se (μg/L) G1: 124.5 ± 24.7 G2: 126.6 ± 26.9 G3: 127.2 ± 24.8

PSA (ng/mL)

G1: 6.4 (5.6) G2: 7.2 (6.2)

G3: 6.9 (4.5)

Se intake: NR

Selenised yeast (200 μg Se/d or 400 μg Se/d or) vs placebo

Adherence, pill counts (%) G1: 92.1 G2: 93.2

G3: 91.2

Incidence of prostate cancer, biopsy‐proven (primary endpoint). Tissue samples from the subject's qualifying biopsy requested from the subject's physician and compiled in a biospecimen repository.

HR for risk of prostate cancer (95% CI) (adjusted for age at baseline, race, baseline PSA, and baseline plasma Se concentration)

G1: 1 (ref) G2: 0.94 (0.52, 1.7)

G3: 0.90 (0.48, 1.66)

Lippman et al. (2009)

Klein et al. (2011)

SELECT

USA, Canada, Puerto Rico

RCT

G1, placebo: 8,856/8,696 G2, 200 μg Se/d: 8,910/8,752 Duration (median (min‐max)): 5.46 (4.17–7.33) yr (+ additional 3 yr of follow up)

Aged ≥ 50 yr (African American men) or 55 yr or older (all other men); serum PSA ≤4 ng/mL; DRE not suspicious for prostate cancer

Sex: M

Age (yr, median (IQR)) G1: 62.6 (58.1–67.8) G2: 62.6 (58.2–68.0)

BMI (kg/m 2 ): NR

Ethnicity (Caucasian, %): 79

Serum Se (μg/L, median (IQR)) G1: 137.6 (124.7–151.8) G2: 135.0 (123.4–145.9)

PSA (ng/mL, mean (IQR))

G1: 1.1 (0.6–1.9) G2: 1.1 (0.6–1.9)

Se intake: NR

L‐selenomethionine (200 μg Se/d) vs placebo

Adherence, pill counts (%) G1: 85% at yr 1; 69% at yr 5

G2: 84% at yr 1; 69% at yr 5

Serum Se at 4 yr, μg/L (median (IQR))

G1: 140.1 (124.3–150.8)

G2: 251.6 (218.7–275.0)

Incidence of prostate cancer determined by routine clinical management. Prostate cancer status was determined by self‐report at each 6‐mo study visit; pathology report and tissue forwarded to the central pathology laboratory for confirmation of diagnosis

N prostate cancer cases; HR for risk of prostate cancer (95% CI)

By end of intervention period:

G1: 416¦G2: 432; 1.04 (0.90, 1.18), p = 0.62

Intervention period + 3 yr of follow up:

G1: 529¦G2: 575; 1.09 (0.93, 1.27), p = 0.18

Of which, prostate cases with Gleason ≥7

G1: 133¦G2: 161; 1.21 (0.90, 1.63), p = 0.11

Marshall et al. (2011)

USA

RCT

G1, placebo: 225/134

G2, 200 μg Se/d: 227/135

Duration: 3 yr

Aged ≥ 40 yr; biopsy‐ confirmed diagnosis of high‐grade prostatic intraepithelial neoplasia with no evidence of cancer; PSA ≤ 10 ng/mL; AUA symptom score < 20; ambulatory and able to carry out work of a light or sedentary nature.

Sex: M

Age (yr): ≥ 40

BMI < 25¦> 30 kg/m 2 (%)

G1: 26.1¦27.5

G2: 21.7¦26.4

Ethnicity (White, %) G1: 76.8 G2: 83.5

Plasma Se, μg/L (median (IQR))

G1 (n = 51): 135.2 (113.3, 166.8) G2 (n = 46): 138.1 (104.7, 166.4)

PSA < 4 ng/mL¦4–10 ng/mL (%)

G1: 42.6¦57.4 G2: 38.2¦61.8

Se intake NR

Selenomethionine (200 μg Se/d) vs placebo

Adherence, pills count (%), at 1 yr; 3 yr

G1: 90.8; 81.3

G2: 90.5; 78.9

Plasma Se (median, μg/L), at 1 yr; 3 yr

G1 (n = 51): 145.7; 152.1

G2 (n = 46): 240.4; 261.2

Incidence of prostate cancer; biopsy proven. DRE every 6 mo. Tissue blocks and corresponding

pathology reports for all prostate procedures submitted to the central study pathologist for review (blinded to study assignment)

N prostate cancer cases; RR for prostate cancer (95% CI)

G1: 47¦G2: 45; 0.97 (0.68, 1.39)

By quartile of baseline plasma Se

< 106 μg/L

G1: 11¦G2: 9; 0.82 (0.40, 1.69)

106–132 μg/L

G1: 9¦G2: 12; 1.38 (0.68, 2.78)

132–162 μg/L

G1: 16¦G2: 14; 0.98 (0.58, 1.68)

> 162 μg/L

G1: 11¦G2: 10; 0.91 (0.45, 1.84)

Duffield‐Lillico et al. (2003a)

NPC

USA

RCT

G1, placebo: 470

G2, 200 μg Se/day: 457

Duration (mean, max): 7.6 yr, 13 yr

Confirmed histories of nonmelanoma skin cancer within the year before randomisation; estimated 5‐year life‐expectancy; no cancer within the previous 5 years.

Sex: M

Age (yr) G1: 63.7 ± 9.4 G2: 64.9 ± 8.8 BMI (kg/m 2 )

G1: 25.9 ± 3.7 G2: 26.0 ± 3.6 Ethnicity: NR

Plasma Se (μg/L) G1: 115.1 ± 22.0 G2: 115.1 ± 22.1

PSA (ng/mL)

G1: 1.9 (3.3)

G2: 2.0 (3.4)

Se intake: NR

Selenised yeast (200 μg Se/d) vs placebo

Adherence NR

Participants visited the clinics every 6 mo and reported new illnesses and medications; medical records documenting any cancer screening procedures (PSA tests, DRE, prostate biopsies and surgery) obtained throughout the course of the trial. Incident prostate cancer cases reviewed and staged by a urological oncologist according to the TNM system.

N prostate cancer cases; HR for prostate cancer (95% CI) (adjusted for age and smoking)

G1: 42¦G2: 22; 0.48 (0.28, 0.80)

By tertile of baseline plasma Se

≤ 106.4 μg/L

G1: 15¦G2: 2; 0.14 (0.03, 0.61)

106.8–123.2 μg/L

G1: 16¦G2: 7; 0.33 (0.13, 0.82)

> 123.2 μg/L

G1: 11¦G2: 13; 1.14 (0.51, 2.59)

AUA: American Urological Association; BMI: body mass index; CI: confidence interval; d: day; DRE: digital rectal examination; Gx: group x; HR: hazard ratio; IQR: interquartile range; M: males; mo: month; NBT: Negative Biopsy Trial; NPC: Nutritional Prevention of Cancer Trial; NR: not reported; PC: prostate cancer; PSA: prostate specific antigen; RCT: randomised controlled trial; Se: selenium; SELECT: Selenium and Vitamin E Cancer Prevention Trial; TNM: tumour, nodes, and metastases; USA: United States of America; yr: year.

(a) Duration = duration of the treatment phase, unless specified otherwise.

(b): Mean ± SD, unless specified otherwise.