Serum prostate-specific antigen (PSA) concentration is positively associated with rate of disease reclassification on subsequent active surveillance prostate biopsy in men with low PSA density

Abstract

Objective: To investigate the association between serum prostate-specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy ('biopsy reclassification') in men with low PSA density (PSAD). To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification.

Patients and methods: We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men). We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS. We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer.

Results: The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8-17.2%) when compared with ≥6 to <8 ng/mL (8.4, 95% CI 5.7-12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4-26.1%). The adjusted predicted IRs of reclassification showed a similar non-linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL.

Conclusion: Risk for biopsy reclassification increased non-linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision-making for AS. However, longer follow-up times are needed to warrant final conclusions.

Keywords: PSA; active surveillance; patient selection.

Fig. 1

A, Age and prostate volume adjusted IRs (per 100 person years) of biopsy reclassification on surveillance biopsy as a function of serum PSA concentration at AS entry. The solid line represents the estimated IR from a Poisson regression model and the shaded area the 95% CI around the estimate. The one PSA concentration of ≥15 ng/mL was truncated for plotting. At the top of the figure the unadjusted IRs are shown in PSA concentration intervals of 2 ng/mL. B, Age and prostate volume adjusted IR (per 100 person years) of disease status reclassification by upgrade on surveillance biopsy as a function of serum PSA concentration at AS entry. The solid line represents the estimated IR from a Poisson regression model and the shaded area the 95% CI around the estimate. The one PSA concentration of ≥15 ng/mL was truncated for plotting. At the top of the figure the unadjusted IRs are shown in PSA concentration intervals of 2 ng/ml.