Summary of First Four Prostate, Lung, Colorectal, and Ovarian Screening Roundsa continued...
A study specifically tested whether total PSA velocity (tPSAv) improves the accuracy of total PSA level (tPSA) to predict long-term risk of prostate cancer. In the 1974 to 1986 Swedish Malmo Preventive Medicine cardiovascular risk study, 5,722 men younger than 51 years gave two blood samples about 6 years apart. Four thousand nine hundred-seven of the archived plasma samples were analyzed for tPSA. Prostate cancer was subsequently diagnosed in 443 (9%) of the men via the Swedish National Cancer Registry through December 31, 2003. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index (similar to the area under the receiver operating characteristic).
The median time from the second blood draw to cancer diagnosis was 16 years. Median follow-up for men not diagnosed with prostate cancer was 21 years. PSA assays were done in plasma stored under conditions that preserved the integrity of PSA. TPSA and tPSAv were highly correlated. Both tPSA and tPSAv were associated with prostate cancer in univariate models (P < .001). Men subsequently diagnosed with prostate cancer have increased tPSA and increased tPSAv up to 20 years before diagnosis. Overall predictive accuracy of tPSA plus tPSAv was equivalent to tPSA alone (concordance index: 0.771 tPSA alone; 0.712 tPSAv alone; 0.771 tPSAv added to tPSA). TPSAv did not aid long-term prediction of cancer in early middle-aged men.
In the PCPT, full ascertainment was attempted, regardless of PSA value; PSA velocity added no independent value to the prediction of prostate cancer after adjustment for family history, age, race/ethnicity, PSA, and history of prostate biopsy. For this reason, in the PCPT risk calculator, PSA velocity is not an included variable.
Alteration of PSA cutoff level
A number of authors have explored the possibility of using PSA levels lower than 4.0 ng/mL as the upper limit of normal for screening examinations. One study screened 14,209 white and 1,004 African American men for prostate cancer using an upper limit of normal of 2.5 ng/mL for PSA. A major confounding factor of this study was that only 40% of those men in whom a prostate biopsy was recommended actually underwent biopsy. Nevertheless, 27% of all men undergoing biopsy were found to have prostate cancer. Several collaborating European jurisdictions are conducting prostate cancer screening trials, Rotterdam (the Netherlands) and Finland among them. In Rotterdam, data for 7,943 screened men between the ages of 55 and 74 years have been reported. Of the 534 men who had PSA levels between 3.0 ng/mL and 3.9 ng/mL, 446 (83.5%) had biopsies and 96 (18%) of these had prostate cancer. In all, 4.7% of the screened population had prostate cancer. In Finland, 15,685 men were screened and 14% of screened men had PSA levels of at least 3.0 ng/mL. All men with PSAs higher than 4.0 ng/mL were recommended to diagnostic follow-up by DRE, ultrasound, and biopsy; 92% complied, and 2.6% of the 15,685 men screened were diagnosed with prostate cancer. Of the 801 men with screening PSAs between 3.0 ng/mL and 3.9 ng/mL (all biopsied), 22 (3%) had cancer. Of the 1,116 men with screening PSAs between 4.0 ng/mL and 9.9 ng/mL, 247 (22%) had cancer; of the 226 men with screening PSAs of at least 10 ng/mL, 139 (62%) had cancer. Several factors could have contributed to these differences, including background prostate cancer prevalence, background screening levels, and details regarding diagnostic follow-up practices; the necessary comparative data are not available.