Prostate specific antigen assay standardization bias could affect clinical decision making.

Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
The Journal of urology (Impact Factor: 3.75). 10/2008; 180(5):1959-62; discussion 1962-3. DOI: 10.1016/j.juro.2008.07.036
Source: PubMed

ABSTRACT Although prostate specific antigen is widely used to detect and manage prostate cancer, many patients and physicians are unaware of which prostate specific antigen assay is being used. Most commercial prostate specific antigen assays are standardized to the WHO 90:10 standard or aligned with the original Hybritech assay with potentially disparate results.
A total of 1,916 men participated in a prostate cancer screening study in 2007. On the day of collection prostate specific antigen was tested from the same serum sample using the Access (Hybritech standard) and ADVIA Centaur (WHO 90:10 prostate specific antigen standard) assays. We examined the differences between the 2 assays and the effect that this might have on clinical decisions.
Median prostate specific antigen was 0.9 and 1.05 ng/ml for the Centaur and Access assays, respectively, representing a 17% difference. Mean prostate specific antigen was 3.45 and 4.79 ng/ml, respectively, representing a 38% difference. Using a prostate specific antigen threshold of 2.5 ng/ml 5% of men would have been recommended to undergo biopsy using the Access but not the Centaur assay. Furthermore, prostate specific antigen differed by greater than 0.4 ng/ml in 26%, greater than 0.75 ng/ml in 14.5% and greater than 2 ng/ml in 4.5% of men in the same sample simply by using the different assays.
In our prospective screening population median prostate specific antigen was 17% lower using WHO vs Hybritech based assay standardization. As such, if these assays were instead used on a serial basis in the same patient, this could lead to false acceleration or false deceleration in prostate specific antigen velocity. Thus, the assay may influence the likelihood of prostate biopsy and, thereby, prostate cancer detection.

  • Reviews in urology 01/2013; 15(4):204-206.
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Reported prostate-specific antigen (PSA) values may differ substantially between assays with the Hybritech and World Health Organization (WHO) standardization. [-2]proPSA (p2PSA) and the Beckman Coulter prostate health index (phi) are newly approved serum markers, which are associated with prostate cancer risk and aggressiveness. Our objective was to study the influence of assay standardization on these markers. MATERIALS AND METHODS: PSA, % free PSA (%fPSA), and p2PSA were measured using the Hybritech calibration in 892 men undergoing prostate biopsy from a prospective multicenter study. Phi was calculated as: [p2PSA/ fPSA) x (square root of PSA)]. Performance characteristics of phi for prostate cancer detection were then determined using re-calculated WHO calibration PSA values. RESULTS: The median phi was significantly higher in men with prostate cancer compared to those with negative biopsies using the WHO values (47.4 vs 39.8, p<0.001). Phi offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to %fPSA or total PSA using the WHO calibration. CONCLUSIONS: Phi can be calculated using Hybritech or WHO standardized assays, and significantly improved the prediction of biopsy outcome over %fPSA or PSA alone.
    The Journal of urology 11/2012; · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Study Type - Prognosis (inception cohort) Level of Evidence 2 What's known on the subject? and What does the study add? A significant proportion of patients diagnosed with prostate cancer do not require immediate treatment and could be managed by active surveillance, which usually includes serial measurements of prostate-specific antigen (PSA) levels and regular biopsies. The rate of rise in PSA levels, which could be calculated as PSA velocity or PSA doubling time, was previously suggested to be associated with the biological aggressiveness of prostate cancer. Although these parameters are obvious candidates for predicting tumour progression in active surveillance patients, earlier studies that examined this topic provided conflicting results. Our analysis showed that PSA velocity and PSA doubling time calculated at different time-points, by different methods, over different intervals, and in different sub-groups of active surveillance patients provide little if any prognostic information. Although we found some significant associations between PSA velocity and the risk of progression as determined by biopsy, the actual clinical significance of this association was small. Furthermore, PSA velocity did not add to the predictive accuracy of total PSA. OBJECTIVE: •  To study whether prostate-specific antigen (PSA) velocity (PSAV) and PSA doubling time (PSADT) are associated with biopsy progression in patients managed by active surveillance. PATIENTS AND METHODS: •  Our inclusion criteria for active surveillance are biopsy Gleason sum <7, two or fewer positive biopsy cores, ≤20% tumour present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. •  This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. •  We evaluated the association between PSA kinetics and progression at successive surveillance biopsies in different sub-groups of patients by calculating the area under the curve (AUC) as well as sensitivity and specificity of different thresholds. RESULTS: •  Over a median follow-up of 3.0 years, the disease of 64 (26%) patients progressed. •  PSADT was not associated with biopsy progression, whereas PSAV was only weakly associated with progression in certain sub-groups. •  However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analysed. In other sub-groups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: •  Our findings confirm that PSA kinetics should not be used in decision-making in patients with low-risk prostate cancer managed by active surveillance. •  Regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.
    BJU International 06/2012; · 3.13 Impact Factor