Elsevier

European Urology

Volume 50, Issue 1, July 2006, Pages 70-75
European Urology

Prostate Cancer
Tumour Features in the Control and Screening Arm of A Randomized Trial of Prostate Cancer

https://doi.org/10.1016/j.eururo.2005.11.005Get rights and content

Abstract

Objective

To compare tumour characteristics at the time of diagnosis of cancers detected in the screening and control arm at the Rotterdam section of the European Randomized study of Screening for Prostate Cancer.

Methods

Data were retrieved from the Rotterdam section of the ERSPC. Men were randomized to the screening arm (n = 21,210) or the control arm (n = 21,166). Men randomized to screening were offered PSA testing every 4 years. Through linkage with the cancer registry, men randomized to the control arm were detected. The biopsy Gleason score was determined in 1,591 and 373 patients in the screening and control arm, respectively. TURP, radical prostatectomy (RP) and cystoprostatectomy were evaluated for Gleason score, pathological (p)T stage and tumour volume.

Results

More prostate cancers were detected in the screening arm (15.9 vs. 4.2 per 1000 man years, p < 0.0001). Clinical stage distribution as well as biopsy and RP Gleason score distribution were significantly less favourable in the control arm. The incidence in man years of advanced disease (i.e. T4/N1/M1) was higher in the screening arm (6.0 per 100,000) as compared to the control arm (4.6 per 100,000). The 5-year PSA progression free survival after RP was 68% in the control arm and 89% in the screening arm (p < 0.0001). The proportion of Incidental prostate cancers was 9.3% of all cancers detected in the control arm.

Conclusions

Although the number of men with advanced prostate cancer is slightly higher in the screening arm, the proportion of prostate cancers with favourable features is increased in the screening arm as compared to that in the control arm.

Introduction

The changing incidence in prostate cancer in the Western world is mainly due to PSA driven testing and the increase in life expectancy. PSA screening is thought to be a powerful tool to detect prostate cancer in an early stage, while curable [1]. The primary goal of the European Randomized study of Screening for Prostate Cancer (ERSPC) is to evaluate whether population based screening reduces mortality from prostate cancer at an acceptable price in terms of quality of life and costs [2], [3]. It is expected that at the end of 2009 conclusive data on the influence of screening on prostate cancer mortality by comparison of both trial arms of the ERSPC will be available.

Comparison of histopathological features of prostatectomies performed on men of the screening arm of the ERSPC with those of a historical control group [4] of the same hospital demonstrated a decreased frequency of lymph node positive disease and a relative increase in proportion of Gleason score 8–10 cancers. However, a comparison of pathological features of all cancers detected in the screening and control arm of the Rotterdam section of the ERSPC was not reported previously.

Incidentally identified prostate cancer can be detected in approximately 10% of trans-urethral resection of the prostate (TURP) specimens. Tumours classified as pT1a diagnosed at TURP are considered as clinically indolent and with low biological potential with favourable follow-up and therefore they are usually managed by watchful waiting [5]. Detection of a substantial proportion of pT1a prostate cancers in the control arm may increase the prostate cancer specific survival in the control arm. Incidental prostate cancer may be detected in about 40% of cystoprostatectomy specimens obtained from men treated for a bladder cancer. These prostate cancers mostly have prognostically favourable features [6].

The present analysis of histopathological features of cancers detected within the control and trial arm of the Rotterdam section of the ERSPC was performed to demonstrate whether population based screening for prostate cancer would lead to the increased detection of prostate cancers with favourable and unfavourable characteristics.

Section snippets

Patients and screening strategies

In the Rotterdam section of the European Randomized Screening Study for Prostate Cancer (ERSPC) 42,376 men, 55–75 years old, were randomized to a screening (n = 21,210) and a control arm (n = 21,166). The follow-up of prostate cancer detection in the control arm was complete until the 1st of July 2003. Information on prostate cancer of men in the control arm was obtained through a record linkage with the Dutch cancer registry. Prostate cancer incidence was calculated per 1000 man-years. Man-years

Prostate cancer incidence

Until July 2003, a total of 1,596 and 464 of prostate cancers were diagnosed, which corresponded to a cumulative incidence of 7.5% and 2.2% in the screening and control arm, respectively. In man-years, the incidence in the screen and the control arm was 15.9 and 4.2 per 1000 men years, respectively (p < 0.0001).

Pre-treatment tumour characteristics

Patients in the control arm had significantly higher PSA levels at prostate cancer diagnosis and a lower proportion of clinical T1c prostate cancer, compared to the screening arm (Table 1

Discussion

The significantly higher prostate cancer detection rate in the screening arm (15.9 per 1000 man years) as compared to the control arm (4.2 per 1000 men years) is associated with a shift in clinical stage and Gleason score distribution of detected cancers. Our data of the diagnostic samples (needle biopsies, TURP) of both arms of the trial now provide direct evidence that the cancers detected in the screening arm have more favourable characteristics as compared to those in the control arm. A

Conclusions

The prostate cancer detection rate in the control arm is significantly lower compared to its rate in the screening arm. Tumours in the screening arm do have more favourable tumour characteristics compared to the control arm, but advanced disease is slightly more frequently detected in the screening arm.

Acknowledgement and details of funding

Supported by grants EUR-94-869 and EUR-98-1757 (to Erasmus University Rotterdam) from the Dutch Cancer Society and grants 002-22820 and 2000-2-1016 (to Erasmus University Rotterdam) from The Netherlands Organization for Health Research and Development (ZONMw), by 5th Framework program grant QLRI-2000-01741 (to Erasmus University Rotterdam) from the European Union, and by Europe Against Cancer. Furthermore we would like to thank the employees and pathologists of Pathologisch Laboratorium

References (18)

There are more references available in the full text version of this article.

Cited by (35)

  • Impact of Early Diagnosis of Prostate Cancer on Survival Outcomes

    2015, European Urology Focus
    Citation Excerpt :

    In radical prostatectomy series, a common pathologic definition for insignificant PCa is localised disease, Gleason score ≤6, and tumour volume <0.5 ml [41]. Using these criteria results in estimates of overdiagnosis ranging from approximately 5% to 31.6% [40,42]. A third method used to estimate the rate of overdiagnosis in a screening situation is to calculate lead time [39].

  • Modified gleason grade of prostatic adenocarcinomas detected in the PLCO cancer screening trial

    2014, Journal of Urology
    Citation Excerpt :

    These comparative data suggest that more intensive screening for prostate cancer may result in the detection of more lower grade and potentially indolent (modified Gleason score 6) cases. Similar data on the grade of screen detected prostate cancers were reported from the Rotterdam section of ERSPC with lower Gleason scores in radical prostatectomy tissues in the screening arm than in the control arm.16,17 However, to our knowledge again it is not known whether these Gleason scores were classic or modified scores.

  • Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer

    2010, European Journal of Cancer
    Citation Excerpt :

    Endocrine therapy was offered much more often in the control arm (22% versus 8% in the screening arm) and surgery and expectant management more often in the screening arm, 37% versus 28% in the control arm for surgery and 21% versus 15% in the control arm for expectant management. These observations are in line with other studies comparing the tumour features and applied treatments of screen detected and clinically diagnosed prostate cancers.4,5,17–19 However, when comparing tumour characteristics of the last period (2003–2006) in the control arm with tumour characteristics of cancers detected at the initial screening round we observed similarities.

  • Eleven-Year Outcome of Patients with Prostate Cancers Diagnosed During Screening After Initial Negative Sextant Biopsies

    2010, European Urology
    Citation Excerpt :

    While the ERSPC study as a whole [1] showed the relative effects of screening in reducing PCa mortality by 20% in the intention-to-screen analysis, and by 30% for those men who in fact get screened [2], a very unfavorable number needed to treat (NNT) of 48 to save 1 PCa death at 9 yr of follow-up with respect to the control group resulted. While more aggressive screening may result in the detection of some aggressive PCa, which may be saved, most additional PCa are likely to be detected in the low PSA ranges, where nonaggressive PCa accumulate [33,34]. More detection of potentially indolent PCa will increase overdiagnosis, overtreatment, and the NNT.

View all citing articles on Scopus
View full text