Elsevier

European Urology

Volume 68, Issue 3, September 2015, Pages 354-360
European Urology

Platinum Priority – Prostate Cancer
Editorials by Neil E. Martin on pp. 361–362 of this issue and by Monique J. Roobol on pp. 363–364 of this issue
Opportunistic Testing Versus Organized Prostate-specific Antigen Screening: Outcome After 18 Years in the Göteborg Randomized Population-based Prostate Cancer Screening Trial

https://doi.org/10.1016/j.eururo.2014.12.006Get rights and content

Abstract

Background

It has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown.

Objective

To compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening.

Design, setting, and participants

The Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012.

Outcome measurements and statistical analysis

Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990–1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates.

Results and limitations

At 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval [CI] 0.50–0.94%) and relative risk reduction of 42% (95% CI 28–54%). There was an absolute reduction in PC deaths of 0.20% (95% CI –0.06% to 0.47%) and a relative risk reduction of 12% (95% CI –5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107–200) and 13 for organized biennial screening and 493 (95% CI 213– −1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy.

Conclusions

Organized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program.

Patient summary

Prostate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening.

Introduction

It has been shown that screening for prostate cancer (PC) with prostate-specific antigen (PSA) testing reduces PC-specific mortality but carries a high risk of overdiagnosis [1], [2]. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) at 13 yr of follow-up, 781 men needed to be invited to screening and 27 men needed to be diagnosed to prevent one PC death [2]. However, no country has yet introduced a national PSA-based screening program, so PSA measurements performed on asymptomatic men with no prior PC diagnosis, aside from those enrolled in organized screening trials, are taken as part of opportunistic PSA testing.

Several studies on breast and cervical cancer screening have indicated that opportunistic screening is less effective and less cost-effective than an organized approach [3], [4], [5] and the Council of the European Union has recommended that screening for breast, cervical, and colorectal cancer should be conducted in organized programs [6]. It is currently unknown whether opportunistic PSA testing is as effective as organized PSA screening in reducing PC mortality, and whether there is a relationship between organized screening versus opportunistic testing and the risk of overdiagnosis. Despite the lack of evidence in support of opportunistic screening, there is high uptake of this form of PSA testing in many Western countries [7], [8], [9], [10]. According to a recent estimate, >50% of all Swedish men aged 55–69 yr have had a PSA test [10], which has resulted in rapidly increasing PC incidence during the last decades [11], [12].

The aim of this study was to investigate the effectiveness of organized and opportunistic screening in reducing PC mortality, measured as the number needed to invite (NNI), and the amount of overdiagnosis, estimated as the number needed to diagnose (NND), in the Swedish center of the ERSPC.

Section snippets

Patients and methods

After approval by the ethics committee at the University of Gothenburg in 1994, the Göteborg randomized population based prostate cancer screening trial was established in 1995 (registered as Current Controlled Trials ISRCTN54449243). Since 1996, the study has contributed to the Swedish arm of ERSPC. The Göteborg study has previously been described in depth [1]. In summary, 20 000 of the men recorded in the population register as living in Gothenburg (born 1930–1944) were computer-randomized,

Results

Following randomization, a total of 101 men were excluded (Fig. 1). During 18 yr of follow-up, 1396 men were diagnosed with PC in the screening group, of whom 1022 were diagnosed as a result of organized screening, compared to 962 cancer cases detected among controls, of whom 361 were asymptomatic men diagnosed by opportunistic screening. In the screening group, 87% complied with the biopsy recommendation. The median age and PSA at diagnosis were 65.8 yr (interquartile range [IQR] 62.2–68.3 yr)

Discussion

To the best of our knowledge, this is the first study comparing organized and opportunistic PSA screening using NNI and NND. The results indicate that similar to breast and cervical cancer screening, organized screening is more effective than opportunistic screening in reducing disease-specific mortality. After 18 yr, PC incidence in the control group had increased by almost 70% compared to the pre-screening era, indicating considerable uptake of opportunistic screening in the control group.

Conclusions

Our results indicate that organized intense screening effectively reduces PC mortality but is associated with considerable overdiagnosis; after 18 yr of follow-up, 13 men must be diagnosed to prevent one PC death compared to a situation with no PSA testing. Opportunistic PSA testing had little if any effect on PC mortality, and was associated with greater overdiagnosis in comparison to organized screening, as estimated by NND. If, after careful counseling, a man chooses to participate in PSA

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