Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology

Claus Roehrborn, Allison Gregory, John D. McConnell, Arthur I Sagalowsky, Frank H. Wians

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objectives. To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. Methods. Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a 'gold standard' for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. Results. Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. Conclusions. In this study in which a 'gold standard' based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
JournalUrology
Volume48
Issue number6 SUPPL.
DOIs
StatePublished - Dec 1996

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Prostate-Specific Antigen
Prostate
Histology
Serum
Prostatic Neoplasms
Prostatic Hyperplasia
Area Under Curve
Prostatectomy
Sensitivity and Specificity
Immunoradiometric Assay
Transurethral Resection of Prostate
ROC Curve

ASJC Scopus subject areas

  • Urology

Cite this

Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology. / Roehrborn, Claus; Gregory, Allison; McConnell, John D.; Sagalowsky, Arthur I; Wians, Frank H.

In: Urology, Vol. 48, No. 6 SUPPL., 12.1996, p. 23-32.

Research output: Contribution to journalArticle

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abstract = "Objectives. To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. Methods. Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a 'gold standard' for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. Results. Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6{\%} for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. Conclusions. In this study in which a 'gold standard' based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15{\%}, 17{\%}, 19{\%}, or 21{\%}) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.",
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AU - Gregory, Allison

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AU - Wians, Frank H.

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N2 - Objectives. To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. Methods. Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a 'gold standard' for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. Results. Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. Conclusions. In this study in which a 'gold standard' based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

AB - Objectives. To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. Methods. Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a 'gold standard' for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. Results. Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. Conclusions. In this study in which a 'gold standard' based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

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