Elsevier

European Urology

Volume 53, Issue 1, January 2008, Pages 91-98
European Urology

Prostate Cancer
Overall Survival in the Intervention Arm of a Randomized Controlled Screening Trial for Prostate Cancer Compared with a Clinically Diagnosed Cohort

https://doi.org/10.1016/j.eururo.2007.06.001Get rights and content

Abstract

Objectives

This population-based study provides comparisons of prostate cancer characteristics at diagnosis of two cohorts of men from two well-defined geographical areas exposed to different intensities of prostate cancer screening. Overall survival in both cohorts was compared with that in the general population.

Methods

A cohort of 822 men randomized to the intervention arm of a prostate cancer screening trial and subsequently diagnosed with prostate cancer was compared with a nonrandomized cohort of 947 men who were clinically diagnosed with prostate cancer in a geographically neighboring region. In both cohorts, cases were diagnosed with prostate cancer between January 1989 and December 1997. A partitioning of overall survival by variables associated with cancer onset such as age at diagnosis, stage at diagnosis, and grade at diagnosis was performed.

Results

Age at diagnosis, tumor extent at diagnosis, and grade at diagnosis were significantly different between the screened and clinically diagnosed cohort. The 5- and 10-yr survival rates were higher in the screened cohort than in the clinically diagnosed cohort (88.8% vs. 52.4%, and 68.4% vs. 29.6%, respectively). Significant differences in survival were evident for all age, stage, and grade subgroups, except for metastatic disease at diagnosis.

Conclusions

Differences in overall survival favoring the screened population were observed for all baseline characteristics (age, stage, and grade of disease), and these variables may all explain differences in overall survival because screening achieves early diagnosis as well as a stage and grade shift. As observed survival rates in the screened population mirrored those within the general population, the contribution of lead time and overdiagnosis to final patient outcome is considered to be large as well.

Introduction

In previous decades, 50–85% of men with advanced prostate cancer died from their disease, depending on the age and extent of disease at diagnosis [1], [2]. From the early 1990s onward, the prostate cancer mortality rates have slowly declined in the United States [3] and in some European countries [4], [5], [6], [7]. Some have argued that this decrease is due to the application of the serum prostate-specific antigen (PSA) test as a tool for the early detection of prostate cancer [8], [9]. Indeed, PSA determination in serum has contributed to a rapid increase in the incidence of prostate cancer, and a concurrent stage and grade migration to earlier stages and lower grades of disease. However, this effect of screening on grade and stage does not necessarily translate into a reduction of disease-specific mortality as has been shown for lung cancer [10]. Until now, no beneficial effect of prostate cancer screening on mortality using the serum-PSA test, and its subsequent diagnostic and therapeutic sequelae, has been established in properly performed randomized controlled trials.

This study was performed to compare the distribution of prognostic factors at diagnosis in two cohorts of men subjected to different intensities of prostate cancer screening. Furthermore, overall survival in both cohorts was compared with that in the general population. Through this methodology of the expected survival, the magnitude of lead time and overdiagnosis of disease can be estimated. Baseline characteristics of 822 men diagnosed with prostate cancer in the intervention arm of the Dutch section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were compared with those in 947 men clinically diagnosed with prostate cancer in a neighboring geographical region in which prostate cancer screening was not common practice. Cases were diagnosed with prostate cancer during periods of time of similar duration. A partitioning of overall survival by variables associated with cancer onset such as age at diagnosis, stage at diagnosis, and grade at diagnosis was performed in both cohorts [11], [12].

Section snippets

Intervention arm of ERSPC

The ERSPC was designed to study the effect of population-based screening for prostate cancer on prostate cancer mortality and quality of life. Between December 1993 and May 1997, in Rotterdam alone, a total of 20,643 men aged 55–75 yr were identified in the population registry, invited to participate, and, after providing informed consent, randomized to the screening study. A total of 10,456 men were randomized to the intervention arm. Men with a prior diagnosis of prostate cancer were

Baseline characteristics

The characteristics of the 822 men diagnosed with prostate cancer in the intervention arm of the screening trial are presented in Table 1. The median age at diagnosis was 67 yr (range, 55–78). A description of the 947 men in the clinically diagnosed cohort is given in Table 1. The median age at diagnosis was 75 yr (range, 47–95).

Overall survival

The median observation period for patients in the intervention arm was 8.1 yr (range, 0.2–11.6) and 4.8 yr (range, 0.1–13.4) for men in the nonscreened cohort. During

Discussion

The current study provides comparisons of the distribution of prognostic factors and outcomes of two cohorts of prostate cancer patients from two well-defined neighboring geographical areas who were exposed to different intensities of prostate cancer screening. The intervention arm of the ERSPC is known to have a 95% screening coverage, whereas at the end of 2004, approximately 30% of men in the control arm had their PSA level measured at least once [21]. This control arm reflects the intensity

Conclusions

The overall survival rate in a contemporary series of men diagnosed with prostate cancer within a population-based screening trial was longer than that of men in a nonrandomized cohort clinically diagnosed with prostate cancer in an adjacent geographical region. Differences in survival were observed for all ages and for all stages and grades of disease, except for metastatic disease at diagnosis.

Differences in baseline characteristics (age, stage, and grade of disease) between cohorts may all

Conflicts of interest

The authors have nothing to disclose.

Acknowledgements

The ERSPC is supported by grants from the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the European Union, and a grant from Beckman Coulter Hybritech Inc, San Diego, CA, USA.

References (38)

  • S. Tuljapurkar et al.

    A universal pattern of mortality decline in the G7 countries

    Nature

    (2000)
  • P.H. Gann

    Interpreting recent trends in prostate cancer incidence and mortality [editorial]

    Epidemiology

    (1997)
  • P.M. Marcus et al.

    Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up

    J Natl Cancer Inst

    (2000)
  • E.J. Feuer et al.

    Cancer surveillance series: interpreting trends in prostate cancer—part II: Cause of death misclassification and the recent rise and fall in prostate cancer mortality

    J Natl Cancer Inst

    (1999)
  • Roobol MJ, Schröder FH, editor. The European Randomized Study of Screening for Prostate Cancer (ERSPC): rational,...
  • F.H. Schröder et al.

    Evaluation of rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study on Screening for Prostate Cancer

    J Natl Cancer Inst

    (1998)
  • I.W. Van der Cruijsen-Koeter et al.

    Interval carcinomas in the European Randomized Study of Screening for Prostate Cancer (ERSPC)-section Rotterdam

    J Natl Cancer Inst

    (2003)
  • F.K. Mostofi

    Grading of prostatic adenocarcinoma

    Cancer Chemother Rep

    (1975)
  • W.C. Black et al.

    All-cause mortality in randomized trials of cancer

    J Natl Cancer Inst

    (2002)
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