Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study

Andrew J Vickers, David Ulmert, Daniel D Sjoberg, Caroline J Bennette, Thomas Björk, Axel Gerdtsson, Jonas Manjer, Peter M Nilsson, Anders Dahlin, Anders Bjartell, Peter T Scardino, Hans Lilja, Andrew J Vickers, David Ulmert, Daniel D Sjoberg, Caroline J Bennette, Thomas Björk, Axel Gerdtsson, Jonas Manjer, Peter M Nilsson, Anders Dahlin, Anders Bjartell, Peter T Scardino, Hans Lilja

Abstract

Objective: To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified.

Design: Case-control study with 1:3 matching nested within a highly representative population based cohort study.

Setting: Malmö Preventive Project, Sweden.

Participants: 21,277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years.

Main outcome measures: Metastasis or death from prostate cancer ascertained by review of case notes.

Results: Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥ 1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥ 2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group.

Conclusion: Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that HL holds patents for free PSA, intact PSA, and hK2 assays; HL, AJV, and PTS are named as co-inventors on a patent application for a statistical method to predict the result of prostate biopsy; HL has support from NIH, Swedish Cancer Society, and Arctic Partners; PS has support from OPKO Health; and AV has support from GlaxoSmithKline (GSK) and Genomic Heath for the submitted work; HL has a patent and stock relationship with Arctic Partners; PS has a consultancy, patent, stock, and royalties relationship with OPKO; AV has a consultation and honorarium relationship with GSK, Genomic Heath, and OPKO.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793484/bin/vica005641.f1_default.jpg
Fig 1 Cumulative incidence of evidence of metastasis or death from prostate cancer by centile of PSA concentration at various ages
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793484/bin/vica005641.f2_default.jpg
Fig 2 Lorenz curves for death from prostate cancer and 95% confidence intervals for PSA concentration at age 45-49 and 51-55

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Source: PubMed

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