Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50

Abstract

Background: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage ≥T3 or metastases at diagnosis).

Methods: Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974-1986 at ages 33-50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls.

Results: At a median follow-up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% CI, 0.70-0.74; for advanced cancer, 0.75; 95% CI, 0.72-0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% CI, 77%-86%) found in men with PSA above the median (0.63 ng/mL at ages 44-50).

Conclusions: A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low-risk men to be screened less often but increase frequency of testing on a more limited number of high-risk men. This is likely to improve the ratio of benefit to harm for screening.

Figure 1

Replication of the association between PSA at age 44–50 and prostate cancer. The graph shows the predicted probability of any, palpable, or advanced prostate cancer diagnosed 20–25 years after baseline venipuncture, by PSA at age 44–50 in men with a cancer diagnosis through December 31^st, 1999 (black lines) compared to recent cases with a diagnosis from January 1^st, 2000 (red lines).

Figure 2

Long-term risk of prostate cancer according to PSA at age 44–50. Thick blue line, any prostate cancer; thick red line, palpable cancer; thick black line; advanced cancer. Thin lines represent 95% confidence intervals. Shaded area represents quartiles of population-based distribution of PSA values (0.42, 0.63, and 0.95 ng/mL). The curves differ from the curves for any cancer in Figure 1 because the analysis was not restricted to men diagnosed 20–25 years after venipuncture.

Figure 3

Lorenz curves for clinically-diagnosed cancer based on PSA at age 44–50. The x axes give population centiles of PSA and y axes give the cumulative number of cases. Dashed lines represent 95% confidence intervals. The curves can be used to determine the proportion of cancers that could be detected early by screening if screening were risk-stratified by PSA level at age 44–50, with only men above that level recommended for regular PSA testing. a) Any prostate cancer; b) palpable prostate cancer; c) advanced prostate cancer.