Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

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.

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Is it Possible to Provide a Prognosis after Radical Prostatectomy for Prostate Cancer by Means of a Psa Regression Model?

The International Journal of Biological Markers ◽

10.1177/172460080502000205 ◽

2005 ◽

Vol 20 (2) ◽

pp. 112-118 ◽

Cited By ~ 4

Author(s):

M. May ◽

S. Gunia ◽

C. Helke ◽

K.P. Braun ◽

S. Pickenhain ◽

...

Keyword(s):

Radical Prostatectomy ◽

Computer Program ◽

Biochemical Recurrence ◽

Specific Antigen ◽

Compartment Model ◽

Recurrence Free Survival ◽

Free Survival ◽

Two Compartment Model

Background For over 15 years, studies have been done to evaluate the elimination kinetics of the prostate-specific antigen (PSA) after radical prostatectomy. Even though evaluation of PSA regression in the two-compartment model has become established, no clear data are currently available as to whether a statement can be made with regard to tumor prognosis from a computation of the PSA half-life (PSA-HL). This study focuses on the determination of the PSA-HL in the two-compartment model and on its correlation with the biochemical recurrence-free survival. In addition, a computer program is being developed to simplify the determination of PSA-HL. Material and methods Seventy-seven prospective patients were examined who subsequently had a radical prostatectomy at our facility without neoadjuvant or adjuvant hormone deprivation. In addition to preoperative measurement of the PSA value (d0), PSA determinations were carried out postoperatively on days 5, 10 and 60, and at four-monthly intervals thereafter (mean follow-up: 16 months). By means of the computer program developed for this purpose, CTK. TumW, the PSA half-lives for the first (d0–d5, PSA-HL1) and second (d5–d10, PSA-HL2) compartments were subsequently determined and their effect on biochemical recurrence-free survival was assessed. Results PSA-HL1 and PSA-HL2 were 1.89 (± 0.03) and 3.39 (± 0.14) days, respectively. Whilst PSA-HL1 did not permit any prognostic statement, the median PSA-HL in the second compartment between patients with and without disease progression differed significantly (4.44 versus 3.12 days; p<0.001). Discrimination analysis produced a cutoff of 3.8 days for the second compartment; patients with a PSA-HL2 ≥3.8 days had a significantly worse biochemical recurrence-free survival after 18 months than the other patients (27% versus 93%; p<0.001). Conclusion The PSA regression kinetics after radical prostatectomy follows a two-compartment model in which the prognostic value of the PSA-HL1 is limited. When a cutoff of 3.8 days is used, evaluation of the PSA-HL in compartment 2 (d5–10) appears to permit a prognostic statement. Due to the limited postsurgical follow-up, the disease process was only assessed as biochemical recurrence-free survival, and a longer follow-up will be necessary to generate data on progression-free survival.

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