title: Early postoperative plasma transforming growth factor-beta1 is a strong predictor of biochemical progression after radical prostatectomy.
abstract: OBJECTIVE
  Blood levels of transforming growth factor-beta1, interleukin-6 and interleukin-6 soluble receptor have been associated with aggressive primary and metastatic prostate cancer. We hypothesized that patients with increased plasma levels of transforming growth factor-beta1, interleukin-6 and/or interleukin-6 soluble receptor after radical prostatectomy would be more likely to harbor occult metastases, leading to disease progression despite effective local control of disease.
  
  
  METHODS
  Plasma transforming growth factor-beta1, interleukin-6 and interleukin-6 soluble receptor were measured 6 to 8 weeks after surgery in 291 consecutive patients treated with radical prostatectomy for clinically localized disease. Discrimination and validation of multivariate Cox regression models targeting time to biochemical progression were used to quantify the added value of these markers to predictive accuracy (concordance index) after internal validation with 200 bootstrap resamples.
  
  
  RESULTS
  On multivariate analysis adjusting for standard postoperative features postoperative plasma transforming growth factor-beta1 was the only biomarker independently associated with biochemical progression (p <0.001). The addition of postoperative transforming growth factor-beta1 improved the accuracy of the standard postoperative model from 78.4% to 84.1%, representing a 5.7% gain (p <0.001). Of patients who experienced biochemical progression postoperative transforming growth factor-beta1 was significantly higher in those with features of aggressive disease progression, ie development of metastasis, prostate specific antigen doubling time less than 10 months and/or failure to respond to local salvage radiation therapy (p <0.001).
  
  
  CONCLUSIONS
  Postoperative interleukin-6 and interleukin-6 soluble receptor have limited clinical usefulness in prostate cancer. In contrast, postoperative plasma transforming growth factor-beta1 measured 6 to 8 weeks after surgery is a strong predictor of biochemical progression, presumably due to an association with early low volume occult metastases that are at the threshold of clinical progression.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA. Shahrokh.Shariat@UTSouthwestern.edu
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Jochen
authors.initials: J
authors.lastname: Walz
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Claudio
authors.initials: C
authors.lastname: Jeldres
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000601:surgery; D019947:Receptors, Interleukin-6 / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D053773:Transforming Growth Factor beta1