title: Low circulating free and bioavailable testosterone levels as predictors of high-grade tumors in patients undergoing radical prostatectomy for localized prostate cancer.
abstract: OBJECTIVE
  Controversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP).
  
  
  METHODS
  Overall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analyses assessed independent predictors for postoperative aggressive pathological features (i.e., a pathological Gleason score [GS] ≥ 7, extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive surgical margins [PSM]) and GS upgrading.
  
  
  RESULTS
  Low TT, BT, and FT levels were found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median BMI was 26.3 kg/m(2) (range: 17.4-43.9), and prevalence of MetS was 18.9%. Significantly higher rates of pathological GS ≥ 7 were observed in groups with a low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%; P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses demonstrated that only low BT and FT levels were independent predictors of pathological GS ≥ 7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001, respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001, respectively), but there was no significant correlation between low circulating testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04) and MetS (OR = 1.19; P = 0.01) were only correlated with PSM.
  
  
  CONCLUSIONS
  Hypogonadism, obesity, and MetS were not independent predictors of pathological GS ≥ 7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels, which might logically result in an active androgen-depleted environment, were linked with high-grade PCa.
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France; UPMC Univ Paris 06, GRC5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, Paris, France.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Léon
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France; UPMC Univ Paris 06, GRC5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seisen
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France; UPMC Univ Paris 06, GRC5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Drouin
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cattarino
authors.affiliation: Academic Department of Pathology, Pitié-Salpétrière Hospital AP-HP, Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.affiliation: Academic Department of Radiology, Pitié-Salpétrière Hospital AP-HP, Paris, France.
authors.forename: Raphaële
authors.initials: R
authors.lastname: Renard-Penna
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mozer
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France.
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Bitker
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, AP-HP, Paris, France; UPMC Univ Paris 06, GRC5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, Paris, France. Electronic address: morgan.roupret@psl.aphp.fr.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D007006:Hypogonadism / Q000150:complications; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D008875:Middle Aged; D060787:Neoplasm Grading; D009765:Obesity / Q000150:complications; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone
keywords: Hypogonadism; Prognostic factor; Prostate cancer; Radical prostatectomy; Testosterone