This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shariat, S. F. Articles by Karakiewicz, P. I. Search for Related Content PubMed PubMed Citation Articles by Shariat, S. F. Articles by Karakiewicz, P. I.

External Validation of a Biomarker-Based Preoperative Nomogram Predicts Biochemical Recurrence After Radical Prostatectomy

Shahrokh F. Shariat, Jochen Walz, Claus G. Roehrborn, Alexandre R. Zlotta, Paul Perrotte, Nazareno Suardi, Fred Saad, Pierre I. Karakiewicz

From the Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec; and Department of Urology, Mount Sinai and Princess Margaret Hospitals, University of Toronto, Toronto, Ontario, Canada; Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany; and the Department of Urology, University of Texas Southwestern Medical Centre, Dallas, TX

Corresponding author: Shahrokh F. Shariat, MD, Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9110; e-mail: shahrokh.shariat{at}utsouthwestern.edu

Purpose: Biomarker signatures currently are used in several malignancies to guide clinical decision making. Recently, preoperative plasma levels of transforming growth factor-β1 (TGF-β1) and interleukin-6 soluble receptor (IL6-SR) have improved the accuracy of a clinical nomogram that predicted biochemical recurrence after radical prostatectomy. However, this model was never externally validated. We tested the accuracy of this nomogram in an independent, external cohort.

Patients and Methods: Preoperative plasma levels of TGF-β1 and IL6-SR were measured in 423 consecutive men who underwent radical prostatectomy and bilateral lymphadenectomy and were used, along with preoperative prostate-specific antigen levels, biopsy Gleason sum, and clinical stage to determine nomogram-derived probabilities of biochemical recurrence–free survival at 5 years after radical prostatectomy. The accuracy of predictions was quantified with the area under the curve (AUC) and calibration plots that graphically displayed the nomogram's performance characteristics. The statistical significance of the difference between the biomarker nomogram and a model designed on the basis of clinical variables alone was tested by using the Mantel-Haenszel statistic.

Results: Biochemical recurrence–free survival at 5 years was 77.0% (95% CI, 72.0% to 82.0%). The biomarker-based nomogram was 87.9% accurate versus 71.1% for the nomogram designed on the basis of clinical variables alone (16.8% difference; P < .001). The performance characteristics of the biomarker-based nomogram were superior to those of the clinical nomogram.

Conclusion: We confirm that plasma levels of TGF-β1 and IL6-SR considerably enhance the accuracy of the standard preoperative nomogram for the prediction of biochemical recurrence after radical prostatectomy. This model further refines our ability to identify patients at a high risk of biochemical recurrence after radical prostatectomy.

Supported in part by the University of Montreal Heath Center Urology Associates, Fonds de la Recherche en Santé du Québec, the University of Montreal Department of Surgery and the University of Montreal Health Center Foundation (P.I.K.); and by the grant of the Vereinigung Norddeutscher Urologen (J.W.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				E. A. Klein, A. J. Stephenson, D. Raghavan, and R. Dreicer Systems Pathology and Predicting Outcome After Radical Prostatectomy J. Clin. Oncol., August 20, 2008; 26(24): 3916 - 3917. [Full Text] [PDF]