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Endocrine treatment (ET) has in the past been shown to be beneficial in delaying clinical progression in all stages of prostate cancer, leading to an improvement of progression free survival in virtually all trials ever conducted. The first observations on this issue date back to the studies of the Veterans Administration Cooperative Urological Research Group in the 1960s. The period of time during which ET and the resulting side effects can be avoided is strongly dependent on the clinical stage of the disease. This treatment period is long in men who have minimal disease, such as a rising prostate-specific antigen after potentially curative management; however, it is considerably shorter in men who initially present with metastatic disease. In these situations, the potential benefit in quality of life, and avoidance of adverse events must be matched against the benefit in terms of gaining progression free time for the individual patient. This difficult task is supported by information supplied in this review. Locally advanced and regional (lymph node positive; stage T3N0-1M0Gx) disease is the domain of adjuvant ET. In this field, important progress has recently been made due to trials, which combine aggressive treatment of the primary tumor with adjuvant ET initiated at the same time. Therefore, in locally advanced and regional disease, radiotherapy or surgery combined with adjuvant ET must be considered state-of-the-art. [ABSTRACT FROM AUTHOR]

PURPOSE:: The European Randomized Study of Screening for Prostate Cancer investigates the impact of screening on prostate cancer mortality and contributes to a better understanding of available screening tests. The present study evaluates the predictive value of a prostate specific antigen (PSA) increase to PSA 3.0 ng/ml or greater in a 4-year period in men who present with low PSA values (less than 3.0 ng/ml) at first screen.MATERIALS AND METHODS:: A total of 42,376 men were randomized to screening vs control in Rotterdam. Of 6,467 men 5,771 had PSA values of less than 3.0 ng/ml, did not undergo biopsy at baseline and were rescreened after 4 years with PSA 3.0 ng/ml or greater as biopsy indication. PSA progression in a 4-year interscreening interval is evaluated by determining the positive predictive values, detection rates and parameters of aggressiveness of round 2 cancers.RESULTS:: PSA progression to more than 3.0 ng/ml occurred in 0.9%, 9.3% and 48.6% of men who presented with PSA values less than 1.0, 1 to 1.9 and 2 to 2.9 ng/ml, respectively, in round 1. Their respective positive predictive values amounted to 19.0%, 23.8% and 27.9%. Cancer detection rates increased with increasing PSA values in round 1. The distribution of low, moderate and high risk cancers depends on round 2 but not on round 1 PSA ranges.CONCLUSIONS:: PSA progression to the (arbitrary) cutoff value of 3.0 ng/ml and the diagnosis of prostate cancer in round 2 screening with a 4-year interval depends strongly on PSA values at the time of the 1st screen. These observations will be helpful to design future screening procedures. With levels less than 2.0 ng/ml PSA progression to levels of 3.0 ng/ml or greater is rare as it was seen only in 4.8% of all men. [ABSTRACT FROM AUTHOR]

The extent of effective prostate-specific antigen (PSA) contamination in the Rotterdam section of the ongoing European Randomized Study of Screening for Prostate Cancer (ERSPC) trial was evaluated and defined as when opportunistic PSA testing of ≥ 3.0 ng/ml was followed by biopsy, similar to the regular procedure within the trial. Records of participants aged 55–74 years at entry were linked to the regional database of the general practitioner (GP) laboratory to obtain PSA tests requested by GPs in the period 1 July 1997 to 31 May 2000 (2.9 years), and to the national pathology database to quantify the number of biopsies. All men randomized were included, only those with prostate cancer screen-detected or clinically diagnosed before July 1997 were omitted from the analyses. 2,895 out of the 14,349 men (20.2%) in the control arm and 1,981 out of the 14,052 men (14.1%) in the screening arm were PSA-tested, at an average annual rate of 73 and 52 per 1,000 person-years, respectively. These rates were higher than those recorded at the national and regional levels, 33 and 38 per 1,000 person-years, respectively. Opportunistic PSA testing in the control arm reached a peak within the first months of randomization, after which it decreased to around 70 per 1,000 person-years. An opposite pattern was observed in the screening arm, where participants already had received the scheduled screening within the trial. The proportion of men in the control arm with PSA ≥ 3.0 ng/ml followed by biopsy and prostate cancer was 7–8% and 3%, respectively (3% and 0.4–0.6% in the screening arm), over the whole study period. Over a 4-year rescreening interval, the average PSA and effective contamination amount were approximately 28% and 10%, respectively. PSA testing in the control arm in the Rotterdam ERSPC section is high, but was not followed by a substantial increase in prostate biopsies. Although the reasons for ordering PSA test or indicating biopsy are unknown, effective PSA contamination in the Rotterdam ERSPC section is low and not likely to jeopardize the power of the trial. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]