Advances in the diagnosis and management of prostate cancer have been associated with changes in clinico-epidemiological characteristics and cancer-specific mortality. Secular trends of prostate cancer patients and its correlation with PSA implementation and the introduction of combined radiation and hormonal therapy (RT+HT) were assessed in a cohort of 910 cancer patients with histologically confirmed prostate cancer diagnosed between 1992 and 2005, and included in a hospital-based database. Relative survival before and after 1999 (when RT+HT for locally advanced disease was introduced) was compared. The mean age at diagnosis decreased from 72.9 years in 1992-1996 to 68.7 in 2003-2005 and the median PSA from 34 to 8 ng/ml. In patients with stages II and III, there was an increase in the indication of RT with or without HT and a decrease in the indication of surgery (from 87.5% to 44.2%). The overall relative 5-year survival increased from 67.3% (95% CI 60.2-75.2) to 92.9% (95% CI 87.3-98.9). The same trend in stage II and stage III cancer patients was found. There was an increase in survival coincidentally with a shift towards lower stages and PSA levels at presentation. Besides other factors, changes in death rates since 1999 could be explained by secular variations in the treatment of the disease, particularly the implementation of RT+HT in intermediate and high-risk locally advanced prostate cancer.