Biological aggressiveness of prostate cancer in the Finnish screening trial

Abstract

Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55-67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. ' 2008 Wiley-Liss, Inc.Key words: prostate neoplasms; prostate cancer; screening; prostatespecific antigen; proliferation antigen Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the Western world and is the second most frequent cause of cancer-related deaths in men.1 More than 95% of malignant prostate neoplasms are adenocarcinomas, and in general, the term prostate cancer is used to designate primary adenocarcinoma. However, prostate cancer comprises a wide spectrum of biological and clinical behavior, ranging from a minute latent tumor to a highly aggressive, life-threatening disease.2 Today, majority of prostate cancers are detected based on serum prostatespecific antigen (PSA). The ultimate goal of prostate cancer screening is to reduce the disease-specific mortality. However, because the biological behavior and the natural course of prostate cancer and its relation to PSA is not known, controlled randomized screening studies are needed to evaluate the effects of early detection and treatment of cancer in mortality and in quality of life.3 The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a multicenter, randomized trial, which started in 1994. 4 Within the ERSPC, approximately 193,000 men from 8 European countries have been randomized, of whom approximately 40% are from Finland with a sample size of approximately 80,000 men. ) is a protein that recognizes nuclear antigens in the cell cycle from the late G1 phase, in S and G2 phases to M phase but not in noncycling cells in G...

Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study

“…However, to our knowledge, there are no studies conducted on a large conservatively treated cohort with outcome data, where decisions on future treatment could be indicated, and a very recent paper (Laurila et al, 2009) suggested that further studies are needed to show the final outcome of proliferative activity in patients with watchful waiting.…”

“…It has been investigated on TURP material (Feneley et al, 1996), biopsy material (Szende et al, 1999;Cowen et al, 2002;Ojea et al, 2004) and radical prostatectomy series (Bettencourt et al, 1996;Moul, 1999;Zudaire Bergera et al, 2000;Inoue et al, 2005) in large screening programmes (Laurila et al, 2009) and after radiation therapy . Some of these show that Ki-67 is an independent predictor of outcome on multivariate analysis .…”

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