Stage shift in PSA-detected prostate cancers - effect modification by Gleason score.
Pashayan N., Pharoah P., Neal DE., Hamdy F., Donovan J., Martin RM., Greenberg D., Duffy SW.
OBJECTIVE: This paper aims to investigate whether the stage shift (where more cancers are detected at an earlier stage) in prostate-specific antigen (PSA)-detected cancers differs by Gleason score. METHODS: Between 2002 and 2005, 1514 men aged 50-69 years were identified with prostate cancer following community-based PSA testing as part of the ProtecT study. In the same period, 2021 men aged 50-69 years with clinically diagnosed prostate cancer were registered at a population-based cancer registry in the East of England. Using logistic regression analysis and controlling for age, the odds ratio (OR) for advanced stage (TNM stage T3 and above) prostate cancer among the PSA-detected group was compared with the clinically diagnosed tumours. The evidence that stage shift differs by Gleason score was assessed using the likelihood ratio test for interaction. RESULTS: Advanced stage disease among the PSA-detected cancers was less common than among the clinically detected cancers (OR = 0.47, 95% CI 0.39-0.56). PSA-detected tumours had a substantial shift to earlier-stage disease where the Gleason score was <7 (OR = 0.52; 95% CI 0.36-0.77, P < 0.001) but showed no such shift where the Gleason score was 7 or more (OR = 0.84; 95% CI 0.66-1.07, P = 0.1). There was evidence of interaction between detection mode and Gleason score (P = 0.03). CONCLUSION: The observed stage shift could be partially explained by length bias or overdiagnosis. These findings may have implications on understanding pathways of prostate cancer progression and on identifying potential targets for screening, pending further investigation of complexities of associations between PSA testing, Gleason score, and stage.