Background: New prognostic grade groupings were recently proposed for prostate cancer. They are based on Gleason grading of either biopsy or prostatectomy specimen. Former Gleason 6 corresponds to group 1, Gleason 7=3+4 corresponds to group 2, Gleason 7=4+3 corresponds to group 3, Gleason 8 corresponds to group 4, and Gleason 9-10 correspond to group 5. Objective: To assess the prognostic value of Gleason grade groups in men with prostate cancer from a nationwide population‑based cohort. Design, Setting and Participants: From the National Prostate Cancer Register of Sweden, we identified 5,880 men diagnosed with prostate cancer from 2005 to 2007, including 4,325 who had radical prostatectomy and 1,555 treated by radiotherapy.  Outcome Measurements and Statistical Analysis: Kaplan-Meier survival analysis was used to calculate the cumulative 4-year biochemical recurrence-free survival. Cox proportional hazards regression models were used to examine the relationship between prognostic Gleason grade groups and biochemical recurrence after radical prostatectomy and radiotherapy. The 4-year biochemical progression-free survival was compared for groups based on biopsy and prostatectomy Gleason grade groups. Results and Limitations: Among men undergoing surgery, the 4‑year biochemical progression-free survival was 89%, 82%, 74%, 77%, and 49% for prognostic Gleason grade groups 1-5 on biopsy. The corresponding 4-year biochemical progression-free survival based on prostatectomy prognostic Gleason grade groups was 92%, 85%, 73%, 63%, and 51% for prognostic Gleason grade groups 1-5. For men undergoing radiotherapy, biopsy prognostic Gleason grade groups 1-5 had 4-year biochemical progression-free survival of 95%, 91%, 85%, 78%, and 70%. After adjusting for preoperative serum prostate specific antigen and clinical stage, biopsy prognostic Gleason grade groups were significant independent predictors of biochemical progression after radical prostatectomy and radiotherapy. There was no central review of pathology. Conclusions: These results confirm the prognostic value of the newly proposed prognostic Gleason grade groups in men undergoing radical prostatectomy and radiotherapy in a population-based setting.

Increased possibilities during the last decades for early detection of prostate cancer have sparked research on preventable or treatable risk factors and on improvements in therapy. Treatments of the disease still entail significant side effects potentially affecting men during the rest of their lives. The studies of the present thesis concern different aspects of prostate cancer from etiological risk factors and factors influencing treatment to an improved methodology for the detection of treatment side effects. Papers I, II, both based in the population based cohort ULSAM (Uppsala Longitudinal Study of Adult Men), investigate possible risk factors of prostate cancer with options for intervention: selenium levels and the metabolic syndrome. The phenomenon of competing risk of death from other causes than prostate cancer and its impact on and importance for choice of statistical methods is also exemplified and discussed for the first time in prostate cancer research. -Smokers with low selenium status have an increased future risk of later development of prostate cancer. Influence of genetic variability appears plausible. -The metabolic syndrome and especially its increased waist circumference component are associated with later development of prostate cancer – taking competing risks of death from other causes into account. Papers III and IV using pharmacoepidemiological methods investigate aspects of drug utilisation in prostate cancer using nationwide and international databases. In Paper III factors influencing anti-androgen use in prostate cancer are investigated, both from a prescriber- and patient perspective.  The age and disease risk group of the patient, unsupported scientifically, influence both the prescribers’ choice of dose and the patients’ adherence to treatment. -Adherence, not previously investigated in male cancer patients, was considerably higher than reported for adjuvant breast cancer treatment. Subgroups of men suitable for intervention to increase adherence were identified. Paper IV, investigates the feasibility of improving an established method for screening large adverse drug reactions databases, the proportional reporting ratio (PRR), this by using restricted sub-databases according to treatment area (TA), introducing the concept of PRR-TA. -The PRR-TA method increases the signal-noise relationship of analyses; a finding highly relevant for possibly conserving manual resources in Pharmacovigilance work in a drug-authority setting.