Prostate Cancer Aggressiveness Is Strongly Dependent of Overweight and Obesity and Related to Androgen Deficiency

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: SAT 0279-0298-Hormone Dependent Tumors
Translational
Saturday, June 21, 2014: 1:00 PM-3:00 PM
Hall F (McCormick Place West Building)

Poster Board SAT-0285
Jean Pierre Raynaud, PHD, DSC1, Yann Neuzillet, MD PhD2, Frank Giton, PhD3, Jean Fiet, MD, PhD4, Thierry Lebret, MD, PhD2 and Henry Botto, MD2
1university Pierre & Marie Curie, Paris, France, 2Hopital Foch, Suresnes, France, 3APHP CIB CHU Sud Henri Mondor, Creteil, France, 4INSERM IMRB CHU Henri Mondor, Creteil, France
INTRODUCTION AND OBJECTIVES: In prostate cancer (PCa) patients, obesity has been associated with worse outcome, especially more frequent biochemical recurrence after radical prostatectomy and low testosterone (<3ng/mL) with tumor aggressiveness, assessed by the predominant Gleason pattern (prdGP). This study aims to compare histological feature with patient’s gonadal status to identify an accurate predictor of high-risk disease before undergoing radical prostatectomy.

METHODS: From a prospective study of 431 PCa patients requiring radical prostatectomy, 296 preoperative sera have been stored at -70°C to assay, in a specialized laboratory in GC-MS, Testosterone (T), bioavailable T (bioT), Dihydrotestosterone (DHT), Δ4-Androstenedione (Δ4), Δ5-Androstenediol (Δ5), Dehydroepiandrosterone (DHEA) and DHEA-sulphate (S-DHEA), Androsterone (ADT), Estradiol (E2), Estrone (E1) and E1-sulphate (S-E1). Gleason score and predominant Gleason pattern (prdGP) were determined in prostate tissue specimens, and crosschecked by two uro-pathologists.

RESULTS: The testosterone GC-MS values were stratified according to T (<3; 3-4; 4-5; 5-6; 6-7 ;>7 ng/mL) leading to 6 groups (N= 27; 39; 63; 72; 35; 60) with an increase in mean T (2.4; 3.4; 4.6; 5.4; 6.4; 8.0 ng/mL), respectively. Parallel increase was observed for bioT (0.97; 1.30; 1.44; 1.50; 1.87; 1.89 ng/mL), DHT (0.19; 0.29; 0.40; 0.53; 0.59; 0.74 ng/mL), and, to a lesser extent, for ADT (0.17; 0.21; 0.18; 0.20; 0.21; 0.24 ng/mL) and for Δ5 (0.51; 0.75; 0.93; 1.06; I.15; 1.38 ng/mL). E2 increased slightly (23; 27; 28; 28; 30; 34 pg/mL). The E2/T ratio went down from 9.8 to 4.2 at the highest T concentrations. The other steroids assessed were stable.

The body mass index (BMI) decreased  (29.9; 27.2; 26.2; 26.0; 25.0; 25.2) from low to high T. When the patients were stratified according to normal BMI <25, n=121, overweight BMI 25-30, n=131 and obese BMI >30, n=44, the mean BMI was 22.7, 27.1, and 32.8, respectively. The prostate weights were similar (49; 46; 52 g).

In the tissue specimens, a slight increase in GS (6.8; 6.9; 7.0) was observed. The incidences of prdGP 4 were 25% in the normal group and 32% in the overweight group: they were statistically different (p=0002, P=0.003) with the incidence of 50% in the obese group. The corresponding hormone levels in each groups were, for T: 5.9; 5.2; 4.6 ng/mL statistically lower in the obese group (p= 0.004 and p=0.04) as well as for DHT: 0.55; 0.47; 0.40 ng/mL (p= 0.0004 and P=0.003). E1 (43 pg/mL) in the obese group was significantly higher (p=0;03) than the 39 and 37 recorded in the normal and overweight groups.

CONCLUSIONS: In diagnosed PCa patients, the pre-operative ratio T/E2 should be used to evaluate the hormonal milieu because it is strongly related to body composition and obesity. Supplementation with testosterone in obese prostate cancer might be useful to reduce the aggressiveness of their cancer.

Nothing to Disclose: JPR, YN, FG, JF, TL, HB

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