Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer

Abstract

Background:Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer.Methods:This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated.Results:The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: −4.7 (3.1) kg vs −2.2 (4.4) kg (P=0.0508); caloric intake: −500 (636) vs −159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs −1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs −48.3 (203.7) ng dl−1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l−1 (P=0.0023); and leptin: −2.16 (2.6) vs −0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2.Conclusions:Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics

“…These data which show the lack of impact of diet, exercise or weight loss on Ki67 join the three aforementioned exercise interventions, as well as a presurgical diet and exercise trial among 34 men with prostate cancer, and a presurgical metformin trial that produced modest weight loss among 200 breast cancer patients, all showing no significant differences in markers of tumor proliferation. However, data from the current study clearly differ from a forerunning presurgical WLI that our group conducted on 34 men with prostate cancer, and another conducted among 87 Barrett's esophagus patients, that showed increased rather than decreased Ki67 among patients assigned to the diet and exercise interventions vs . controls.…”

Reply to “Phase II prospective randomized trial of weight loss prior to radical prostatectomy”

“…Abbreviated study periods and complicated logistics make these trials challenging. We speak from experience, since we completed a trial of similar design [ 2 – 4 ]. While Henning et al discussed our trial [ 1 – 3 ], our findings were not presented, possibly due to publication overlap [ 4 ].…”

“…We speak from experience, since we completed a trial of similar design [ 2 – 4 ]. While Henning et al discussed our trial [ 1 – 3 ], our findings were not presented, possibly due to publication overlap [ 4 ]. Both trials were undertaken with the same scientific premise: weight loss would slow tumor proliferation and reduce biomarkers of insulin signaling, inflammation, and androgenic control.…”

“…Henning et al [ 1 ] prescribed a structured diet plan of 1200 or 1500 kcal/day that utilized meal replacements and 1 h/day of aerobic, resistance training, and stretching exercises. In our trial [ 2 , 4 ], men were counseled to achieve dietary deficits of 1000 kcal/day and 250 kcal/day of aerobic exercise.…”

“…Henning et al [ 1 ] stopped accrual early; 44 participants were enrolled and 34 (18 controls/16 WLI) completed. Our accrual target of 40 was achieved, and we had 34 trial completers (16 controls/18 WLI) [ 4 ]. Samples were similar, with men of mean age 60–63, body mass indexes of 30–33, and ~30% African-Americans.…”