Abstract
If prostate-specific antigen (PSA) trends help identify elevated prostate cancer (PCa) risk, they might provide early warning of progressing cancer for further evaluation and justify annual testing. Our objective was to determine whether PSA trends predict PCa likelihood. A biopsy cohort of 361,657 men was obtained from a Veterans Affairs database (1999–2012). PSA trends were estimated for the 310,458 men with at least 2 PSA tests prior to biopsy. Cancer tumors may grow exponentially with cells doubling periodically. We hypothesized that PSA from prostate cancer grows exponentially above a no cancer baseline. We estimated PSA trends on that basis along with five descriptive variables: last PSA before biopsy, growth rate in PSA from cancer above a baseline, PSA variability around the trend, number of PSA tests, and time span of tests. PSA variability is a new variable that measures percentage deviations of PSA tests from estimated trends with 0% variability for a smoothly increasing trend. Logistic regression models were used to estimate relationships between the probability of PCa at biopsy and the trend variables and age. All five PSA trend variables and age were significant predictors of prostate cancer at biopsy (p < 0.0001). An overall logistic regression model achieved an AUC of 0.67 for men with at least 4 tests over at least 3 years, which was a substantial improvement over a single PSA (AUC 0.58). High probability of PCa was associated with low PSA variability (smooth trends), high PSA, high growth rate, many tests over a long time-span and older age. For example, at 4.0 PSA the probability of cancer is 32% for 1 PSA test and increases to 68% for 8 tests over 7 years with smooth, fast growth (0% variability and 50% exponential growth). Our results show that smooth, fast exponential growth in PSA above a baseline predicts an increased probability of PCa. The probability increases as smooth (low variability) trends are observed for more tests over a longer time span, which makes annual testing worth considering. Worrisome PSA trends might be used to trigger further evaluation and continued monitoring of the trends—even at low PSA levels.
Highlights
Screening for prostate cancer (PCa) using the prostate-specific antigen (PSA) blood test is controversial
The United States Preventative Services Task Force (USPSTF) has been skeptical of the net benefits of PSA screening for men of all ages and recently revised their draft recommendation for men ages 55–69 years, suggesting “individualized decision-making after discussion with a clinician, so that each man has an opportunity to understand the potential benefits and harms of screening and to incorporate his values and preferences into his decision” (C recommendation with D recommendation against PSA-based screening for men age 70 years and older) [4]
Using the Veterans Affairs (VA)’s large multi-center cohort of men with PSA history who underwent prostate biopsy, we demonstrated that PSA trend variables predict the probability of PCa diagnosis at biopsy
Summary
Screening for prostate cancer (PCa) using the prostate-specific antigen (PSA) blood test is controversial. There is evidence that PSA screening reduces prostate cancer deaths when a low PSA threshold, such as 3.0, is used to trigger a biopsy [1,2,3]. New panels of blood tests [7,8,9], ultrasound imaging [10], and multi-parametric MR imaging [11] appear to offer substantial improvements over PSA screening in terms of identifying high risk prostate cancers. Online risk calculators [12, 13] consider more variables than PSA and allow personal risk assessment They may provide men and their physicians with enough confidence to delay or avoid biopsies that might be premature using only PSA and a low threshold. Delay or avoidance of premature biopsies would reduce potential harms and make screening more appealing
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