Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability

Abstract

Background: Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease.

Methods: PSA velocity was determined in 980 men (856 without prostate cancer, 104 with prostate cancer who were alive or died of another cause, and 20 who died of prostate cancer) who were participants in the Baltimore Longitudinal Study of Aging for up to 39 years. The relative risks (RRs) of prostate cancer death and prostate cancer-specific survival stratified by PSA velocity were evaluated in the three groups of men by Cox regression and Kaplan-Meier analyses. Statistical tests were two-sided.

Results: PSA velocity measured 10-15 years before diagnosis (when most men had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later; survival was 92% (95% confidence interval [CI] = 84% to 96%) among men with PSA velocity of 0.35 ng/mL per year or less and 54% (95% CI = 15% to 82%) among men with PSA velocity above 0.35 ng/mL per year (P<.001). Furthermore, men with PSA velocity above 0.35 ng/mL per year had a higher relative risk of prostate cancer death than men with PSA velocity of 0.35 ng/mL per year or less (RR = 4.7, 95% CI = 1.3 to 16.5; P = .02); the rates per 100,000 person-years were 1240 for men with a PSA velocity above 0.35 ng/mL per year and 140 for men with a PSA velocity of 0.35 ng/mL per year or less.

Conclusions: PSA velocity may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease.

Fig. 1

Average prostate-specific antigen (PSA) levels in ng/mL as a function of years before diagnosis (prostate cancer) or last visit (no prostate cancer). Subjects who died of prostate cancer (top cross-hatched area); subjects with prostate cancer who where alive or died of another cause (middle cross-hatched area); and subjects without prostate cancer (bottom solid area). Areas represent 95% confidence intervals for PSA levels based on mixed-effects models.

Fig. 2

Distributions of prostate-specific antigen (PSA) levels and PSA velocity at 10–15 years before diagnosis for each study group. A) Distribution of PSA levels. B) Distribution of PSA velocity. Boxes represent the 25th to 75th percentiles (interquartile range = IQR); horizontal lines within boxes, the median values; and vertical lines, 1.5 times the IQR (outliers exceeding 1.5 times the IQR were removed from illustration).

Fig. 3

Kaplan–Meier estimates of prostate cancer–specific survival according to prostate-specific antigen velocity (PSAV) at 10–15 years before diagnosis (prostate cancer) or last visit (no prostate cancer). Estimates of percent survival (with 95% confidence intervals) are shown for men with PSA velocity of 0.35 ng/mL per year or less (solid line) and PSA velocity above 0.35 ng/mL per year (dashed line). P<.001 (two-sided log-rank test for comparison of groups).