Contribution of a Single Repeat PSA Test to Prostate Cancer Risk Assessment: Experience from the ProtecT Study

Abstract

Objective

To examine whether a single repeat prostate-specific antigen (PSA) helps discriminate cancer from non–cancer-related PSA elevation.

Methods

Men aged 50–70 yr (n = 54,087) in a multicentre randomised controlled trial comparing treatments for localised prostate cancer were tested. A total of 4102 (7.6%) with an initial PSA in the range of 3–19.9 ng/ml had repeat measurement (median interval: 50 d) followed by prostate biopsy. The decision to biopsy was based on the first PSA level. The outcome was the presence of prostate cancer on biopsy.

Results

Men with a 20% drop in PSA had a lower risk of cancer (odds ratio [OR] = 0.43; 95% confidence interval [CI], 0.35–0.52; p < 0.001) and high-grade cancer (OR = 0.29; 95%CI, 0.19–0.44; p < 0.001) compared to the rest of the cohort. The effect of percentage reduction was greater in men aged ≤60 yr than in those >60 yr. (OR for any cancer = 1.6; 95%CI, 1.0–2.4; p = 0.05; OR for high-grade cancer = 2.9; 95%CI, 1.2–6.7; p = 0.014). This equated to a risk reduction of high-grade cancer from 4% to 0.5%, 6% to 2%, and 15% to 2% in men ≤60 yr with an initial PSA of 3.0–3.99, 4.0–5.99, and ≥6 ng/ml, respectively. No level of repeat PSA confidently predicted absence of cancer.

Conclusion

Following an initial PSA of 3.0–19.99 ng/ml in men aged 50–70 yr, repeat PSA within 7 wk allows more accurate risk prediction that may assist in the decision-making as to whether or not to proceed with prostate biopsy.

Introduction

Despite limitations of prostate-specific antigen (PSA) as a screening investigation for prostate cancer, PSA testing worldwide remains common; three fourths of men in the United States have had a PSA test performed [1] and the rate of testing is rising in the United Kingdom [2]. Multicentre studies assessing PSA testing in screening for prostate cancer are underway in many countries.

The Prostate Cancer Prevention Trial (PCPT) found a significant prevalence of prostate cancer in men with a PSA level previously considered to be normal [3]. It is now accepted that PSA provides a risk assessment and biopsy is undertaken on the basis of level of risk. The exact level at which to recommend biopsy is controversial; the original cut-off suggested was 4 ng/ml [4], but Catalona et al subsequently recommended 2.5 ng/ml on the basis of similar incidence and pathologic characteristics of cancer at a PSA level of 2.5–4.0 ng/ml [5]. In the European Randomised Study of Screening for Prostate Cancer (ERSPC), Schröder et al concluded the optimal cut-off level was 3.0 ng/ml [6].

Intraindividual fluctuations of 10–20% in the range 0.1–20 ng/ml are described [7], [8]. The causes and clinical significance of such variabilities are unknown. In the present study, the cohort from the Prostate Testing for Cancer and Treatment (ProtecT) study [9] was used to test the hypothesis that short-term variability in PSA levels may contribute useful information. The clinical implications in the context of prostate cancer screening and risk assessment are discussed.