Elsevier

European Journal of Cancer

Volume 46, Issue 17, November 2010, Pages 3068-3072
European Journal of Cancer

Detection rates of cancer, high grade PIN and atypical lesions suspicious for cancer in the European Randomized Study of Screening for Prostate Cancer

https://doi.org/10.1016/j.ejca.2010.09.035Get rights and content

Abstract

The aim of the study

This article presents the incidence of prostate cancer, isolated high grade prostatic intraepithelial neoplasia (PIN) and atypical lesions suspicious for prostate cancer (LSPC) during subsequent screening rounds in the centres of five of the countries participating in the European Randomized Study of Screening for Prostate Cancer (ERSPC). The incidence and predictive value of high grade PIN and LSPC for prostate cancer in subsequent biopsy following these diagnoses were evaluated.

Patients and methods

Study group consisted of 56,653 screened men in the ERSPC centres of Finland, Italy, Netherlands, Sweden and Switzerland, who underwent 3–7 screening rounds at 2–4 year interval. Data for prostate cancer were obtained from the ERSPC central database. Data for high grade PIN and LSPC were gathered from each ERSPC centre. Detection rates of subsequent prostate cancer in the first re-biopsy after these diagnoses were determined.

Results

The average cancer detection rate was 3.5%, 3.2% and 3.5% for the completed rounds 1, 2 and 3, respectively, in all five centres. Incidence of high grade PIN increased from 1.5% in the first round to 5.0% in the third round, varying among centres in the first round between 0.8% and 7.6%. The cancer detection rate in the first re-biopsy after the diagnosis of high grade PIN was 12.9%. Incidence of LSPC was 2.4%, 2.7%, 2.2% and 2.6% in the first, second, third and fourth round, respectively. The cancer detection rate at the first re-biopsy after the diagnosis of LSPC was in average 33.8%.

Conclusions

Cancer detection rate was stable during the three screening rounds. The wide variation in frequency in particular of high grade PIN among the ERSPC centres suggests a considerable inter-observer variation. The average comparatively low detection rate of isolated high grade PIN in the first screening round may be screening-related, while its consistent increase during three screening rounds could be the consequence of a.o. previous screening and ageing of the population. The observed low risk of prostate cancer after isolated high grade PIN in this screening setting is in line with the current recommendation to abstain from early repeat biopsies after this diagnosis. The association of LSPC with high incidence of prostate cancer in re-biopsies confirms the need for early repeat biopsies and follow-up of these men. The low percentage of LSPC (<3% of biopsies) throughout all rounds is reassuring as it limits the biopsy burden in a screening setting.

Introduction

High grade prostatic intraepithelial neoplasia (PIN) is a neoplastic transformation of superficial secretory epithelial cells of prostatic ducts and glands, characterised by cell atypia, prominent nucleoli, secretory cell proliferation and interruption of basal cell layer in architecturally benign glands.1, 2 High grade PIN is generally considered as a precancerous state for prostate cancer, while detectable in at least 70% of prostatectomies containing a prostate cancer.2, 3, 4 The prevalence of isolated high grade PIN in prostate biopsies is reported to show wide variation in the earlier studies. The mean reported incidence of isolated high grade PIN was 9%,3, 4 showing variation from 4.4% to 25% in biopsies from urological practice.4 Lower prevalence of PIN in prostate biopsies has been reported along with increased use of PSA-testing,5 as well as during the PSA screening in one screening centre.6 The clinical significance of isolated high grade PIN is based on the demonstration in older studies of a high risk of subsequent prostate cancer in follow-up biopsies.5, 7 These data have been mainly obtained from studies of non-screened populations. Based on these studies early re-biopsy was recommended for patients with high grade PIN,4 and this recommendation has been followed also in the screening centres. As a consequence a substantial proportion of asymptomatic men screened for prostate cancer needed to undergo an additional biopsy, which is undesirable in a screening setting. However, the reported predictive value of PIN for subsequent carcinoma has decreased during the last years.6, 8 Particularly, studies comparing the incidence of prostate cancer after an initial diagnosis of isolated high grade PIN with that after a benign biopsy diagnosis did not reveal significant differences.5, 7

Lesions suspicious for but not diagnostic of prostate cancer and LSPC have also been called glandular atypia or more commonly ASAP (atypical small acinar proliferation).8 Difficulties to render a definitive diagnosis of cancer in case of small atypical lesions have been shown recently.9 Suspicious lesions have been followed by much higher cancer detection rates than PIN,5, 6, 8 and therefore a re-biopsy has often been recommended by pathologists after LSPC diagnosis.

In the present study the detection rates for prostate cancer, PIN and LSPC in five centres of ERSPC study were determined. A further aim of the study is to identify changes in their incidences during subsequent screening rounds and the risk of cancer detection in subsequent prostate biopsies.

Section snippets

Participating ERSPC centres

In the European Randomized Study of Screening for Prostate Cancer, 182,000 men aged 51–75 years were randomised in a screening arm and a control arm in eight countries. Study group of the present study consists of 56,653 screened men in five ERSPC centres, Finland, Italy, Netherlands, Sweden and Switzerland, who underwent 3–7 screening rounds. Age range at entry was 51–66 years in Sweden, 55–67 years in Finland, 55–75 years in the Netherlands and Italy and 55–69 years in Switzerland.

Results

Average cancer detection rate in the screening arm of the five centres combined during the three first rounds was 3.5%, 3.2% and 3.5% in the first, second and third rounds, respectively (Table 1). Data were based on 17,864 biopsies, from which 4178 cancers were detected – that is an average positive biopsy percentage for all three rounds in the five centres of 23.4% and cancer detection rate of 3.4% (data not shown). When we compare the cancer detection rates per screening round in each of the

Discussion

The rate of cancer detection in the present study was fairly stable during the three rounds, although there was considerable variation between the centres. The rate was lowest in Italy. Reasons for the difference between centres may be due to many factors, for example the comparatively low biopsy compliance in Italy as reported previously.11 The average detection rate of prostate cancer (3.4%) in the five screening centres is higher than the general detection rate in these countries (from 0.8%

Conflict of interest statement

None declared.

References (18)

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