Population Based Screening for Prostate Cancer: prognostic findings of two subsequent screening rounds

Prostate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer incidence increases with higher age. The dilemma of prostate cancer is that more men die with prostate cancer than from prostate cancer, as reflected by the observation that in 70% of men who are 80 years or older prostate cancer is diagnosed histologically on autopsy. As a consequence of this high incidence on autopsy, it may be anticipated that a large proportion of old men are diagnosed with prostate cancer when undergoing prostate biopsy and a great proportion of prostate cancers detected in screening programs may be over-diagnosed. It is as yet unclear whether PSA based screening reduces prostate cancer mortality. Due to screening with PSA most cancers are diagnosed in an early stage and therefore possibly in a curable stage. As a result, cancer is removed in an early stage, before the tumor is able to metastasize. It is conceivable that population-based early prostate cancer screening will reduce prostate cancer mortality. In order to investigate this further, randomized clinical trials have been introduced. In the USA the Prostate Lung Colorectal and Ovary cancer (PLCO) study investigates if prostate cancer screening is justified. In Europe the European Randomized Study of Screening for Prostate Cancer (ERSPC) is conducted in 8 European countries to study whether prostate cancer screening can reduce prostate cancer specific mortality at affordable costs and quality of life. The European screening centers differ with regard to the screening procedure but they share PSA testing and most other features (Table 1). At the Rotterdam section of the ERSPC the screening protocol comprises serum PSA testing followed – in case of an elevated serum PSA level- by six lateralized needle biopsies, three from each side of the prostate (systematic sextant biopsy) in men aged between 55 and 75 years. Every four years the same cohort of men is screenend. Men are excluded from screening in the 2nd round if a previous diagnosis of prostate cancer is made and those with interval carcinoma (i.e. cancers detected after the 1st round, but during the 4-year screening interval period. Unfortunately, the final outcome of the ERSPC will not be here until the end of 2008 or later. This thesis is restricted to an analysis of the data from first and second screening rounds at the Rotterdam section of the ERSPC. Awaiting the final outcome of the ERSPC, the investigations collected in this thesis are aimed to provide insight in 1) intermediate endpoints, concerning stage and grade of prostate cancer in subsequent screening rounds and the forthcoming therapy choices, 2) the efficiency of the screening protocol employed at the Rotterdam section of the ERSPC and 3) the natural biology of prostate cancer and its possible premalignant lesions.