BMJ: PSA @ 40, 50,& 60 clinically indicated.

BMJ 

Research

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

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f2023 (Published 16 April 2013)

Cite this as: BMJ 2013;346:f2023

1. Andrew J Vickers, attending1,
2. David Ulmert, research fellow23,
3. Daniel D Sjoberg, research biostatistician1,
4. Caroline J Bennette, PhD student4,
5. Thomas Björk, associate professor3,
6. Axel Gerdtsson, resident3,
7. Jonas Manjer, associate professor5,
8. Peter M Nilsson, professor6,
9. Anders Dahlin, data manager7,
10. Anders Bjartell, professor3,
11. Peter T Scardino, chair2,
12. Hans Lilja, attending clinical chemist, professor2891011

Author Affiliations

1. Correspondence to: H Lilja, Memorial Sloan-Kettering Cancer Center, 1275 York Ave (Box 213), New York, NY 10065, USA liljah@mskcc.org

• Accepted 13 March 2013

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.

Introduction

Screening for prostate cancer with the prostate specific antigen (PSA) test became widespread long before the availability of randomised evidence as to its value. There is now evidence that PSA screening is associated with reduced mortality from prostate cancer in men who would not otherwise be screened,1 2 although this comes at considerable harms in terms of the number of men who need to be screened, undergo biopsy, and be treated to prevent one man experiencing prostate cancer metastasis or dying.

That said, PSA screening is not a single intervention and men can be screened in different ways. There is surprisingly little evidence to support many aspects of contemporary screening guidelines. In particular, the age at which screening starts and the frequency of PSA testing is rarely justified in terms of empirical data. Recent evidence has suggested that a single PSA measurement can predict the long term risk of clinically relevant prostate cancer.3 4 5 6 This suggests that a baseline concentration could be used to determine whether a man might benefit from subsequent PSA tests and, if so, when these should be administered.

We used data from the Malmö Preventive Project cohort to develop an evidence based schema for prostate cancer testing. We retrospectively analysed PSA in previously unthawed, archived, anticoagulated blood plasma obtained at baseline from a large highly representative population based cohort of men who had not been screened for PSA and had been followed for 25-30 years. As such, the cohort provides a “natural experiment” for investigating the association between PSA and long term prostate cancer outcomes.

Using this cohort, we previously showed that PSA concentration at age 60 can predict the risk of death from prostate cancer by age 85 (AUC of 0.90). In particular, the 25 year risk of death from prostate cancer in men with PSA below the median (≤1 µg/L) is low (0.2%) and suggests that half of the men at age 60 could be exempt from further screening.7 We determined the risk of metastasis or death from prostate cancer within 25-30 years based on PSA measured close to the time when screening is normally recommended to begin. As there was little screening for prostate cancer in our cohort, these results can be used to determine which men are most likely to benefit from screening.