Nationwide analysis: Changes in the natural history of low risk localized prostate cancer

12 Background: Increased use of prostate-specific antigen (PSA) has introduced an increase in PCa incidence and a lead time and stage migration at diagnosis, altering the natural history of PCa. Contemporary PCa patients are likely younger and have smaller tumor burden at diagnosis. We investigated if changes in the PCa landscape have altered the course of low-risk localized PCa. Methods: In the Danish Prostate Cancer Registry (DaPCaR), patients diagnosed from 1995 to 2011 with localized (T1-2, N0/X, M0) PCa with Gleason score ≤ 6 were identified. Patients were stratified into three periods of diagnosis; 1995-2000 (period 1), 2001-2005 (period 2) and 2006-2011 (period 3). Competing risk analysis treating PCa and other-cause death as competing events was performed. Results: Of the 5,660 patients identified, 35.9% had undergone radical prostatectomy (RP). From period 1 to period 3, the median age at diagnosis decreased from 72.2 to 66.0 years and the median PSA decreased from 16.2 to 8.6 ng/mL. From period 1 to period 3, the 5-year risk of PCa-death decreased from 14.3% (95% CI: 12.1-16.4%) to 1.3% (95% CI: 0.83-1.7%), p < .0.0001 and the risk of other cause death decreased from 18.1% (95% CI: 15.8-20.5%) to 7.2% (95% CI: 6.2-8.2), p = 0.0001. In patients undergoing RP, the 5-year risk of PCa-death decreased from 0.67% (95% CI: 0.67-2.0%) for patients diagnosed in period 1 to 0.45% (95% CI: 0.0055-0.84), for patients diagnosed in period 3, p = 0.92. For patients not undergoing RP, the 5-year risk of PCa death decreased from 16.6% (95% CI: 14.1-19.1) to 2.0% (95% CI: 1.2-2.7%), p < 0.0001. Conclusions: In a nationwide cohort of patients with low risk localized PCa, the 5-year risk of PCa-death significantly decreased when comparing patients diagnosed during 2006-2011 to those diagnosed during 1995-2000. This was mainly driven by patients not undergoing RP. In the most recently diagnosed group, the difference in 5-year PCa-death between patients undergoing RP and not undergoing RP was small (0.45% vs. 2.0%). Our data demonstrate that the impact of PSA induced lead-time and stage migration has diminished the absolute effect of RP on the risk of 5-year PCa-death because contemporary low-risk localized patients have a significantly better prognosis.