Long-term outcome among men with conservatively treated localised prostate cancer

Abstract

Optimal management of clinically localised prostate cancer presents unique challenges, because of its highly variable and often indolent natural history. There is an urgent need to predict more accurately its natural history, in order to avoid unnecessary treatment. Medical records of men diagnosed with clinically localised prostate cancer, in the UK, between 1990 and 1996 were reviewed to identify those who were conservatively treated, under age 76 years at the time of pathological diagnosis and had a baseline prostate-specific antigen (PSA) measurement. Diagnostic biopsy specimens were centrally reviewed to assign primary and secondary Gleason grades. The primary end point was death from prostate cancer and multivariate models were constructed to determine its best predictors. A total of 2333 eligible patients were identified. The most important prognostic factors were Gleason score and baseline PSA level. These factors were largely independent and together, contributed substantially more predictive power than either one alone. Clinical stage and extent of disease determined, either from needle biopsy or transurethral resection of the prostate (TURP) chips, provided some additional prognostic information. In conclusion, a model using Gleason score and PSA level identified three subgroups comprising 17, 50, and 33% of the cohort with a 10-year prostate cancer specific mortality of o10, 10 -30, and 430%, respectively. This classification is a substantial improvement on previous ones using only Gleason score, but better markers are needed to predict survival more accurately in the intermediate group of patients.

Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer

“…Univariate and multivariate analysis were performed by proportional hazard (Cox) regression analysis (Cox and Oakes, 1984). All follow-up times commenced at the point of 6 months following diagnosis as in the previous report (Cuzick et al, 2006). Associations between categorical data were examined using the w 2 test and Fisher's exact test when expected cell counts were less than 5.…”

“…Tissue microarrays (TMAs) were constructed from 445 unselected transurethral resection of the prostate specimens taken from patients managed with no initial treatment in a cohort of conservatively managed men with prostate cancer (Cuzick et al, 2006). Patients from this cohort who were initially treated with hormone therapy (Cuzick et al, 2006) were excluded from this study, because the expression of the fusion gene under investigation of TMPRSS2-ERG is controlled by androgens (Tomlins et al, 2005).…”

“…Patients from this cohort who were initially treated with hormone therapy (Cuzick et al, 2006) were excluded from this study, because the expression of the fusion gene under investigation of TMPRSS2-ERG is controlled by androgens (Tomlins et al, 2005). The median age of diagnosis was 70 years (49-76 years) and the median follow-up was 91 months (3-173 months).…”

“…Most men were diagnosed after the age of 65 years. A competing risk analysis showed that after 10 years of follow-up, 50% of men had died: 17% from prostate cancer and 33% from other causes; only 27% were alive without progression (Cuzick et al, 2006). National approval for the collection of the cohort was obtained from the Northern Multi-Research Ethics Committee followed by local ethics committee approval at each of the collaborating hospital trusts.…”

“…To help identify and optimize markers that may be of use in the management of men with prostate cancer, we recently established a retrospective cohort of men whose cancers were conservatively managed (Cuzick et al, 2006). Improving on previous studies (Chodak et al, 1994;Albertsen et al, 1995;Adolfsson et al, 1997;Holmberg et al, 2002;Johansson et al, 2004;Albertsen et al, 2005;Bill-Axelson et al, 2005), our analyses included centrally assigned Gleason scores determined by modern grading criteria, and allowed comparisons with several additional clinical parameters.…”