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Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer

Abstract

Background

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines.

Methods

We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7.

Results

The median PSA-density was 0.10 ng/ml2 (IQR 0.075–0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05–1.07 and OR 1.07, 95% CI 1.06–1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml2 and 0.15 ng/ml2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors.

Conclusions

PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

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Fig. 1: Predicted proportions of cancer findings in 5291 Swedish men aged 50–69 with Prostate-Specific Antigen (PSA) ≥3 ng/ml by PSA-density

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Acknowledgements

We thank all study participants, the STHLM3 core management group for taking care of all contact with participants, organizing the databases and performing analyses; KI Biobank at Karolinska Institutet for taking care of blood sampling and sample handling; Karolinska University Hospital Laboratory for organizing sample handling and analysis; the STHLM3 outpatient urologists taking care of patients and performing biopsies; and Unilabs AB for biopsy handling.

Funding

Funding

This study was supported by grants from the Strategic Research Programme on Cancer (StratCan), Karolinska Institutet; the Linné Centre for Breast and Prostate Cancer (CRISP, 70867901), Karolinska Institutet; the Swedish Research Council (K2010–70X-20430–04–3; 2015-03292); the Swedish Cancer Society (11–0287; 2015/649); Stiftelsen Johanna Hagstrand och Sigfrid Linners Minne; and FORTE 2015-00184. The funding source had no role in the study design; collection, analysis, or interpretation of data; writing of the report; or the decision to submit the article for publication. The researchers were all independent from the funding source.

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Correspondence to Tobias Nordström.

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Conflict of interest

HG and ME have patents pending related to the Stockholm3 test. The remaining authors declare that they have no conflict of interest.

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Nordström, T., Akre, O., Aly, M. et al. Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer. Prostate Cancer Prostatic Dis 21, 57–63 (2018). https://doi.org/10.1038/s41391-017-0024-7

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