Assay standardization bias: different prostate cancer detection rates and clinical outcomes resulting from different assays for free and total prostate-specific antigen.

OBJECTIVES: Numerous commercial assays are available for measuring total and free prostate-specific antigen (PSA) levels in serum. These assays can be referenced to different laboratory standards, and interassay variability occurs. Patients and physicians might be affected by the variability between PSA assays that results from the use of different PSA standards. METHODS: We prospectively compared the free and total PSA measurements obtained using two commercially available PSA assays in 103 participants from a prostate cancer screening program in Caracas, Venezuela. We recommended biopsy to men with a total PSA level of 3 to 10 ng/mL and a free/total PSA ratio of 20% or less with either assay. We compared the sensitivity, specificity, and concordance index between the two assays to assess the effects of interassay variability on the cancer detection rate and clinical outcomes. RESULTS: Although the total PSA results were similar between the assays, the free PSA level was significantly greater with one assay. Therefore, the free/total PSA ratio was discordant between the two assays, resulting in different biopsy recommendations and cancer detection rates. CONCLUSIONS: Using a free/total PSA ratio of 20% or less as the threshold for biopsy, the differences in assay sensitivity and specificity for detecting prostate cancer are significant. Commercially available assays for PSA and its derivatives are not necessarily interchangeable, and these differences might lead to different clinical outcomes. When using free and total PSA measurements to make clinical decisions, patients and physicians should be aware of the potential standardization bias and which assay is being used.

Percent carcinoma in prostatectomy specimen is associated with risk of recurrence after radical prostatectomy in patients with pathologically organ confined prostate cancer.

PURPOSE: We evaluated tumor size, measured as the percent of the prostate involved by cancer, as a predictor of tumor recurrence after radical prostatectomy in patients with pathologically organ confined prostate cancer. MATERIALS AND METHODS: One of us (WJC) performed radical retropubic prostatectomy in 1,850 men who had pathologically organ confined prostate cancer with tumor size recorded between January 1988 and February 2003. The percent of prostate tissue involved by carcinoma in the radical prostatectomy specimen was estimated by visual inspection. We compared clinicopathological characteristics in patients who did and did not have tumor recurrence and stratified them by percent of tumor in the prostatectomy specimen. We also evaluated the relationship between percent of cancer and biochemical evidence of cancer recurrence. RESULTS: Patients who had recurrence were slightly older (mean age 62 vs 60 years, p = 0.004), and had higher mean preoperative prostate specific antigen (8.6 vs 6.3 ng/ml, p <0.0001) and a higher proportion of poorly differentiated tumors (Gleason grades 8 to 10) (7% vs 1%, p = 0.001). The mean percent of cancer was higher in men with recurrence (11% vs 7%, p <0.0001). Men with 10% or greater of the gland involved by cancer had a 10% recurrence rate compared with a 5% rate in men in whom cancer involved less than 10% of the gland (p = 0.001). The 5-year recurrence-free survival rate was 94%, 91% and 82% in patients with less than 10%, 10% to 20% and greater than 20% of the gland involved. The multivariate Cox model indicated that the percent of cancer involvement of the prostate provides unique predictive information about the risk of cancer recurrence (p = 0.0001). The estimated 5-year recurrence-free survival rate based on the Cox model indicated that patients with greater than 20% of the gland involved by tumor, clinical stage T2/T3 and Gleason sum >/=7 were at substantial risk of cancer recurrence. CONCLUSIONS: Tumor size measured as the percent of cancer is an independent predictor of cancer recurrence after radical prostatectomy in patients with pathologically organ confined prostate cancer.