The ERSPC trial openly http://www.selleckchem.com/products/ABT-888.html states that “the benefit from screening was restricted to the core age group of subjects who were between the ages of 55 and 69 at the time of randomization,” and the PLCO trial states that their results support “the validity of the recent recommendations of the US Preventative Services Task Force, especially against screening all men over the age of 75 years.” Ethnic variations are not explored in either trial, and the lack of recruitment of African Inhibitors,research,lifescience,medical American men, who have a higher risk of prostate disease, may have affected the results

of the US-based PLCO trial. The control group and overall population prescreening data make the 2 trials more difficult to compare. The PLCO trial regards those men in the control group as contaminants only if they had repeated screenings, defined as at least twice in 7 or 10 years of follow-up. This may lead to a control group in the PLCO trial that is similar to those in the screening arm of the ERSPC trial. This does not diminish their individual importance, but Inhibitors,research,lifescience,medical does make it more difficult to compare the 2 studies. Differences in the serum PSA levels defined as Inhibitors,research,lifescience,medical a positive result within and between trials could also cloud comparisons. ERSPC used different levels in the different centers in their study and PSA cutoff varied from 3 to 4 ng/mL, with rates necessitating further testing ranging from 2.5 to 3.9 ng/mL; the PLCO study used 4 Inhibitors,research,lifescience,medical ng/mL as

the uniform cutoff rate. Studies in the PSA screening era have BAY 734506 demonstrated a fall in serum PSA level at the time of diagnosis: it has decreased from 11.8 ng/mL in 1990 to 6.3 ng/mL in 1998.17,18 Generally,

a lower PSA value at diagnosis has been associated with better pathologic outcomes and disease-free survival.19 Yet, the high levels of overdiagnosis in these trials show that this association may not be as clear as previously thought. Stage migration has been one of the Inhibitors,research,lifescience,medical most significant changes in the PSA screening era. Catalona and colleagues20 first reported a decrease in advanced prostate cancer in the screened population in 1993. In comparison Cilengitide with the referred population from the same institute, 70% of the prostate cancers detected with PSA screening were pathologically organ confined, in contrast to 51% in the referred population. According to the Center for Prostate Disease Research (CPDR) database, the percentage of patients presenting with metastatic disease decreased from 19.8% in 1989 to 3.3% in 1998.21 Concurrently, data from other American registries also documented falling age-adjusted incidence rates of distant metastasis by approximately 50%.22 Roehl and colleagues23 found that more than 60% of the prostate cancers in the PSA screening era were clinical T1c tumors, compared with more than 70% of the clinical T2 tumors in the pre-PSA screening era. The results from the ERSPC and PLCO trials muddy these waters.