Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL: results from the Göteborg randomized population-based prostate cancer screening trial

Abstract

Abstract

Objective: To evaluate the long-term outcome of men with an initial prostate-specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T PSA) ratio is a useful prognostic marker in this range.

Materials and methods: This study is based on 5,174 men aged 50–66 years, who in 1995–1996 participated in the first round of the Göteborg randomized screening trial (initial T-PSA level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T PSA screening until they reached the upper age limit (on average 69 years). Biopsy was recommended if PSA ≥ 3 ng/mL.

Results: After a median follow-up of 18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of ≤0.99 ng/mL to 26.0% in men with T-PSA levels of 1–1.99 ng/mL and 40.3% in men between 2–2.99 ng/mL (p < 0.001). The initial PSA was also related to the incidence of Gleason ≥7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs 1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of the model (p = 0.371).

Conclusions: Some men with initial PSA < 3 ng/mL will be diagnosed too late, despite participating in an organized screening program, indicating that prompt diagnosis is justified in these men. PC incidence and risk of PC death was associated with PSA., but F/T PSA had no predictive value.

Keywords:

• Prostate cancer
• screening
• PSA
• free-to-total PSA
• mortality

Acknowledgments

We sincerely thank all members of the Göteborg screening trial, particularly Helén Ahlgren and Maria Nyberg for providing administrative support and data management of the study. The authors would also like to acknowledge Professor Ola Bratt for his valuable comments on this paper. The work was supported by Göteborg University [grant number ALFGBG-432981], the Swedish Research Council Grant to J. Hugosson (no. 2016-01973), and the Swedish Cancer Society (no.14-0694), David H. Koch through the Prostate Cancer Research Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers, a Specialized Program of Research Excellence grant; [grant number P50-CA92629] from the National Cancer Institute to Dr. Howard Scher, a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC [grant number P30-CA008748]; a grant from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network (U01CA199338-02), a Swedish Cancer Society Grant to Dr H. Lilja (Cancerfonden no. 14-0722), the Swedish Research Council (VR-MH no. 2016-02974) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in the UK. None of the funding sources had access to the database or were involved in the collection or management of the data. Nor had they any influence on the writing of this paper

Conflict of interest

Hans Lilja holds patents for free PSA., hK2, and intact PSA assays, and is named on a patent application for a statistical method to detect prostate cancer. The marker assay patents and the patent application for the statistical model has been licensed and commercialized as the 4Kscore™ by OPKO Diagnostics. Dr Lilja receives royalties from sales of this test and owns stock in OPKO.