Summary of First Four Prostate, Lung, Colorectal, and Ovarian Screening Roundsa continued...
Because the efficacy of screening depends on the effectiveness of management of screen-detected lesions, trials of treatment efficacy in early-stage disease are relevant to the issue of screening. The Prostate Intervention Versus Observation Trial (PIVOT) is the only published trial conducted in the PSA era that directly compared radical prostatectomy with watchful waiting. From November 1994 through January 2002, 731 men aged 75 years or younger with localized prostate cancer were randomly assigned to one of the two management strategies. About 50% of the men had nonpalpable, screen-detected disease. After a median follow-up of 10 years (maximum up to about 15 years), there was no statistically significant difference in overall or prostate-specific mortality. (Refer to the Treatment Option Overview section in the PDQ summary on Prostate Cancer Treatment for a more detailed description of the study and results.)
Methods to Improve the Performance of Serum PSA Measurement for the Early Detection of Prostate Cancer
As noted above, various approaches aimed at improving the performance of PSA in early cancer detection have been tested. None are clearly more accurate than total serum PSA levels, but these approaches are discussed below.
Prostate cancer gene 3 (PCA3)
PCA3 was approved by the U.S. Food and Drug Administration in early 2012, with the intended use to improve the selection of men with a prior negative biopsy for an elevated PSA for whom a repeat biopsy is being considered for a persistently elevated PSA. This test is performed in a urine sample collected after an "attentive" DRE (several strokes applied firmly to the prostate to right and left prostatic lobes). Using a threshold value of 60, this test enhances the detection of prostate cancer while reducing the number of biopsies in men who will ultimately have a negative biopsy.
Complexed PSA and percent-free PSA
Serum PSA exists in both free form and complexed to a number of protease inhibitors, especially alpha-1-antichymotrypsin. Assays for total PSA measure both free and complexed forms. Assays for free PSA are available. Complexed PSA can be found by subtracting free PSA from the total PSA. Several studies have addressed whether complexed PSA or percent-free PSA (ratio of free to total) are more sensitive and specific than total PSA. One retrospective study evaluated total PSA, free/total, and complexed PSA in a group of 300 men, 75 of whom had prostate cancer. Large values of total, small values of free/total, and large values of complexed PSA were associated with the presence of cancer; the authors chose the cutoff of each measure to yield 95% sensitivity and found estimated specificities of 21.8%, 15.6%, and 26.7%. The preponderance of evidence concerning the utility of complexed and percent-free PSA is not clear, however, total PSA remains the standard.